Biopsychology (Global Edition) Chapter 13: Hormones and Sex - PDF

Chapter 13 Hormones and Sex What’s Wrong with the Mamawawa? Hinterhaus Productions/Getty Images Chapter Overview and Learning Objectives Neuroendocrine System LO 13.1 Explain the distinction between exocrine glands and endocrine...

Chapter 13 Hormones and Sex What’s Wrong with the Mamawawa? Hinterhaus Productions/Getty Images Chapter Overview and Learning Objectives Neuroendocrine System LO 13.1 Explain the distinction between exocrine glands and endocrine glands, describe the functions of the gonads, and distinguish between the X chromosome and the Y chromosome. LO 13.2 Describe the three classes of hormones and then describe three classes of gonadal hormones. LO 13.3 Explain why the pituitary is sometimes called the master gland and describe its anatomy. Discuss the female vs. male patterns of gonadal and gonadotropic hormone release and explain the evidence that discounted a role for the anterior pituitary in controlling those patterns of release. LO 13.4 Explain how the anterior and posterior pituitary are controlled. LO 13.5 Describe the research that led to the discovery of the hypothalamic releasing hormones. LO 13.6 Describe three different types of signals that regulate hormone release. Also, describe how hormones are released over time and the effect this pattern of release has on levels of circulating hormones. 344 M13_PINE1933_11_GE_C13.indd 344 22/01/2021 11:25  Hormones and Sex 345 LO 13.7 Summarize the model of gonadal endocrine regulation. Hormones and Sexual LO 13.8 Describe the development of the internal and external Development of the Body reproductive organs. LO 13.9 Describe the male and female secondary sex characteristics and the role of hormones in their development. Sexual Development of LO 13.10 Describe the evolution of research and thinking about sex Brain and Behavior differences in the brain. LO 13.11 Describe the results of studies of sex differences in behavior in humans and nonhumans. Three Cases of Exceptional LO 13.12 Explain what androgen insensitivity syndrome, adrenogenital Human Sexual syndrome, and ablatio penis have taught us about human Development sexual development. Effects of Gonadal LO 13.13 Describe the role of gonadal hormones in male sexual Hormones on Adults behavior. LO 13.14 Describe the role of gonadal hormones in female sexual behavior. LO 13.15 Describe the dangers associated with anabolic steroid use. Brain Mechanisms of LO 13.16 Describe the roles of the cortex, hypothalamus, amygdala, and Sexual Behavior ventral striatum in sexual activity. Sexual Orientation and LO 13.17 Describe the results of the two studies on the genetics of Gender Identity sexual orientation by Bailey and Pillard (1991, 1993) and describe the fraternal birth order effect and why it is thought to occur. LO 13.18 Describe the hypothesized role of adrenal cortex steroids in the emergence of sexual attraction. LO 13.19 Describe the famous study of LeVay (1991) and two major problems with its finding. LO 13.20 Define gender identity, and explain what is meant by “gender dysphoria.” LO 13.21 Explain how sexual attraction, gender identity, and body type are independent. This chapter is about hormones and sex, a topic that some pair of glands. Because many of us think that our sex regard as unfit for conversation but one that fascinates is ­fundamental and immutable, it could be disturbing to many others. Perhaps the topic of hormones and sex is so think it could be altered with a few surgical snips and some fascinating because we are intrigued by the fact that our hormone injections. And there is something intriguing sex is so greatly influenced by the secretions of a small about the idea that our sex lives might be enhanced by the M13_PINE1933_11_GE_C13.indd 345 22/01/2021 11:25  346 Chapter 13 application of a few hormones. For whatever reason, the topic of hormones and sex is always a hit with our students. Some remarkable things await you in this chapter. Neuroendocrine System This module starts off by introducing the general principles MEN-ARE-MEN-AND-WOMEN-ARE-WOMEN of neuroendocrine function by describing the glands and ­ASSUMPTION. Let’s start with the fact that many stu- hormones directly involved in sexual development and dents bring a piece of excess baggage to the topic of hor- behavior. mones and sex: the men-are-men-and-women-are-women The endocrine glands are illustrated in Figure 13.1. assumption—or “mamawawa.” This assumption is seduc- By convention, only the organs whose primary function tive; it seems so right that we are continually drawn to it appears to be the release of hormones are referred to as without considering alternative views. Unfortunately, it is endocrine glands. However, other organs (e.g., the stomach, fundamentally flawed. liver, and intestine) and body fat also release hormones The men-are-men-and-women-are-women assump- into general circulation (see Chapter 12), and they are thus, tion is the tendency to think about femaleness and male- strictly speaking, also part of the endocrine system. ness as discrete, mutually exclusive, opposite categories. In thinking about hormones and sex, this general atti- tude leads one to assume that females have female sex hormones that give them female bodies and make them Glands do female things and that males have male sex hormones LO 13.1 Explain the distinction between exocrine that give them male bodies and make them do male glands and endocrine glands, describe the things. Despite the fact that this approach to hormones functions of the gonads, and distinguish and sex is inconsistent with the evidence, its simplicity, between the X chromosome and the symmetry, and comfortable social implications draw us to Y chromosome. it (see Carothers & Reis, 2013; Jordan-Young & Rumiati, There are two types of glands: exocrine glands and endocrine 2012). That’s why this chapter grapples with hormones glands. Exocrine glands (e.g., sweat glands) release their and sex throughout and encourages you to think about chemicals into ducts, which carry them to their targets, mostly them in new ways—ways that are more consistent with on the surface of the body. Endocrine glands (ductless glands) the evidence. release their chemicals, which are called hormones, directly DEVELOPMENTAL AND ACTIVATIONAL EFFECTS OF into the circulatory system. Once released by an endocrine SEX HORMONES. Before we begin discussing particular gland, a hormone travels via the circulatory system until it hormones and sex, you need to know that hormones influence Figure 13.1 The endocrine glands. sex in two fundamentally differ- ent ways (see Bale & ­Epperson, 2015): (1) by influencing the development from conception to sexual maturity of the anatomi- cal, ­physiological, and behavioral Pineal characteristics that distinguish Hypothalamus one as female or male; and (2) by activating the reproduction- Pituitary related behavior of sexually Thyroid mature adults (see Wu & Shah, 2011). The developmental (also Parathyroid called organizational) and acti- vational effects of sex hormones Thymus are discussed in different parts of this chapter. However, in real Adrenal life, these effects can occur simul- Pancreas taneously. For example, because Ovary the brain continues to develop into the late teens, adolescent Testis hormone surges can have both effects (see Bell, 2018). M13_PINE1933_11_GE_C13.indd 346 22/01/2021 11:25  Hormones and Sex 347 reaches the targets on which it normally exerts its effect (e.g., Hormones other endocrine glands, sites in the nervous system). LO 13.2 Describe the three classes of hormones GONADS. Central to any discussion of hormones and sex and then describe three classes of gonadal are the gonads—the male testes (pronounced TEST-eez) hormones. and the female ovaries (see Figure 13.1). As you learned in Vertebrate hormones fall into one of three classes: (1) amino acid Chapter 2, the primary function of the testes and ovaries derivatives, (2) peptides and proteins, and (3) steroids. Amino is the production of sperm cells and ova, respectively. After acid derivative hormones are hormones that are synthesized ­copulation (sexual intercourse), a single sperm cell may in a few simple steps from an amino acid molecule; an example ­fertilize an ovum to form one cell called a zygote, which con- is epinephrine, which is released from the adrenal medulla and tains all of the information necessary for the typical growth synthesized from tyrosine. Peptide hormones and protein of a complete adult organism in its natural environment. hormones are chains of amino acids; peptide hormones are With the exception of ova and sperm cells, each cell of the short chains, and protein hormones are long chains. Steroid human body has 23 pairs of chromosomes. In contrast, hormones are hormones that are synthesized from cholesterol, the ova and sperm cells contain only half that number, one a type of fat molecule (see Abruzzese et al., 2018). member of each of the 23 pairs. Thus, when a sperm cell The hormones that influence sexual development and fertilizes an ovum, the resulting zygote ends up with the the activation of adult sexual behavior (i.e., the sex hor- full complement of 23 pairs of chromosomes—one of each mones) are all steroid hormones. Most other hormones pair from the father and one of each pair from the mother. produce their effects by binding to receptors in cell mem- Of particular interest in the context of this chapter is the branes. Steroid hormones can influence cells in this fash- pair of chromosomes called the sex chromosomes, so named ion; however, because they are small and fat-soluble, they because they contain the genetic programs that direct sexual can readily penetrate cell membranes and often affect cells development. The cells of females have two large sex chro- in a second way. Once inside a cell, the steroid molecules mosomes, which are called X chromosomes. In males, one sex can bind to receptors in the cytoplasm or nucleus and, by chromosome is an X chromosome, and the other is called a so doing, directly influence gene expression (amino acid Y chromosome. Consequently, the sex chromosome of every derivative hormones and peptide hormones affect gene ovum is an X chromosome, whereas half the sperm cells expression less commonly and by less direct mechanisms). have X chromosomes, and half have Y chromosomes. Your Most importantly and most relevant to this chapter is that, sex with all its social, economic, and personal ramifications of all the hormones, steroid hormones tend to have the most was determined by which of your father’s sperm cells won diverse and long-lasting effects on cellular function. the dash to your mother’s ovum. If a sperm cell with an X sex chromosome won, you are a female; if one with a SEX STEROIDS. The gonads do more than create sperm and Y sex chromosome won, you are a male. egg cells; they also produce and release steroid hormones. You might reasonably assume that X chromosomes Most people are surprised to learn that the testes and ovaries are X-shaped and Y chromosomes are Y-shaped, but this release the very same hormones. The two main classes of is incorrect. Once a chromosome has duplicated, the two gonadal hormones are androgens and estrogens; testosterone products remain joined at one point, producing an X shape. is the most common androgen, and estradiol is the most This is true of all chromosomes, including Y chromosomes. common estrogen. The fact that adult ovaries tend to release Because the Y chromosome is much smaller than the X chro- more estrogens than androgens and that adult testes release mosome, early investigators failed to discern one small arm more androgens than estrogens has led to the common, but and thus saw a Y. In humans, the smaller Y-chromosome misleading, practice of referring to androgens as “the male sex genes appear to control the synthesis of only 66 proteins (see hormones” and to estrogens as “the female sex hormones.” Rengaraj, Kwon, & Pang, 2015)—in comparison to 615 for This practice should be avoided because of its men-are-men- the larger X-chromosome genes (see Yamamoto et al., 2013). and-women-are-women implication that androgens produce Writing this section reminded me (JP) of my seventh- maleness and estrogens produce femaleness. They don’t. grade basketball team, the “Nads.” The name puzzled our The ovaries and testes also release a third class of teacher because it was not at all like the names usually steroid hormones called progestins. The most common favored by pubescent boys—names such as the “Avengers,” progestin is progesterone, which in females prepares the the “Marauders,” and the “Vikings.” Her puzzlement ended uterus and the breasts for pregnancy. Whether it serves a abruptly at our first game as our fans began to chant their function in males is unclear, but in both males and females support. You guessed it: “Go Nads, Go! Go Nads, Go!” My it seems to be involved in various forms of neuroplasticity 14-year-old, spotted-faced teammates and I considered this (see González-Orozco & Camacho-Arroyo, 2019). to be humor of the most mature and sophisticated sort. The Because the primary function of the adrenal cortex— teacher didn’t. the outer layer of the adrenal glands (see Figure 13.1)—is M13_PINE1933_11_GE_C13.indd 347 22/01/2021 11:25  348 Chapter 13 the regulation of glucose and salt levels in the blood, it is part of the same embryonic tissue that eventually develops not generally thought of as a sex gland. However, in addi- into the roof of the mouth; during the course of develop- tion to its principal steroid hormones, it does release small ment, it pinches off and migrates upward to assume its posi- amounts of all of the sex steroids released by the gonads. tion next to the posterior pituitary. It is the anterior pituitary that releases tropic hormones; thus, it is the anterior pitu- itary in particular, rather than the pituitary in general, that The Pituitary qualifies as the master gland. LO 13.3 Explain why the pituitary is sometimes called FEMALE GONADAL HORMONE LEVELS ARE the master gland and describe its anatomy. CYCLIC; MALE GONADAL HORMONE LEVELS ARE Discuss the female vs. male patterns of gonadal STEADY. Although males and females release exactly the and gonadotropic hormone release and explain same hormones, these hormones are not present at the same the evidence that discounted a role for the levels, and they do not necessarily perform the same func- anterior pituitary in controlling those patterns tions. The major difference between the endocrine function of release. of females and males is that in human females, the levels The pituitary gland is frequently referred to as the master gland of gonadal and gonadotropic hormones go through a cycle because most of its hormones are tropic hormones. Tropic hor- that repeats itself every 28 days or so. It is these more-or- mones’ primary function is to influence the release of hormones less regular hormone fluctuations that control the female from other glands (tropic means “able to stimulate or change menstrual cycle. In contrast—although we hate to admit something”). For example, gonadotropin is a pituitary tropic it—human males are, from a neuroendocrine perspective, hormone that travels through the circulatory system to the rather dull creatures: Males’ levels of gonadal and gonado- gonads, where it stimulates the release of gonadal hormones. tropic hormones change little from day to day. The pituitary gland is really two glands: the posterior Because the anterior pituitary is the master gland, many pituitary and the anterior pituitary, which fuse during early scientists assumed that an inherent difference between the course of embryological development. The posterior the male and female anterior pituitary was the basis for the pituitary (see Figure 13.2) develops from a small outgrowth difference in male and female patterns of gonadotropic of hypothalamic tissue that eventually comes to dangle and gonadal hormone release. However, this hypothesis from the hypothalamus on the end of the pituitary stalk (see was discounted by a series of clever transplant studies Figure 13.3). In contrast, the anterior pituitary begins as conducted by Geoffrey Harris in the 1950s (see Raisman, 2015). In these studies, a cycling pituitary removed from a mature female rat became a Figure 13.2 A midline view of the posterior and anterior pituitary and steady-state pituitary when transplanted at surrounding structures. the appropriate site in a male, and a steady- state pituitary removed from a mature male rat began to cycle once transplanted into a Anterior Massa intermedia female. What these studies established was commissure (connects the two lobes of the thalamus) that anterior pituitaries are not inherently female (cyclical) or male (steady-state); their Hypothalamus patterns of hormone release are controlled by some other part of the body. The master gland seemed to have its own master. Where was it? Control of the Pituitary LO 13.4 Explain how the anterior and posterior pituitary are Optic controlled. chiasm The nervous system was implicated in the Anterior control of the anterior pituitary by behav- pituitary ioral research on birds and other animals that Posterior Mammillary breed only during a specific time of the year. pituitary body It was found that the seasonal variations in the light–dark cycle triggered many of the M13_PINE1933_11_GE_C13.indd 348 22/01/2021 11:25  Hormones and Sex 349 They are then transported along the axons of these neurons Figure 13.3 The neural connections between the hypothalamus and the pituitary. Notice the neural input to to their terminals in the posterior pituitary and are stored the pituitary all goes to the posterior pituitary; the anterior there until the arrival of action potentials causes them to pituitary has no neural connections. be released into the bloodstream. (Neurons that release hormones into general circulation are called neurosecretory Paraventricular cells.) Oxytocin stimulates contractions of the uterus during nucleus of the labor and the ejection of milk during suckling; vasopressin hypothalamus (also called antidiuretic hormone) facilitates the reabsorption of water by the kidneys; and both seem to influence stress-coping and social responses (see Benarroch, 2013; Hammock, 2015; Shen, 2015). The means by which the hypothalamus controls the release of hormones from the neuron-free anterior pituitary was more difficult to explain. Harris (1955) suggested that the release of hormones from the anterior pituitary was itself Supraoptic regulated by hormones released from the hypothalamus. nucleus of the hypothalamus Pituitary Two findings provided early support for this hypothesis. stalk The first was the discovery of a vascular network, the hypothalamopituitary portal system, that seemed well suited to the task of carrying hormones from the hypothalamus to the anterior pituitary. As Figure 13.4 illustrates, a network of hypothalamic capillaries feeds a bundle of portal veins that carries blood down the pituitary stalk into another network of capillaries in the anterior pituitary. (A portal vein is a vein Posterior Anterior pituitary that connects one capillary network with another.) The pituitary second finding was the discovery that cutting the portal veins of the pituitary stalk disrupts the release of anterior pituitary hormones until the damaged veins regenerate (Harris, 1955). breeding-related changes in hormone release. If the lighting conditions under which the animals lived were reversed, Discovery of Hypothalamic for example, by having the animals transported across the equator, the breeding seasons were also reversed. Some- Releasing Hormones how, visual input to the nervous system was controlling LO 13.5 Describe the research that led to the discovery the release of tropic hormones from the anterior pituitary. of the hypothalamic releasing hormones. The search for the particular neural structure that con- It was hypothesized that the release of each anterior pitu- trolled the anterior pituitary turned, naturally enough, to itary hormone is controlled by a different hypothalamic the hypothalamus, the structure from which the pituitary hormone. Each hypothalamic hormone that was thought to is suspended. Hypothalamic stimulation and lesion experi- stimulate the release of an anterior pituitary hormone was ments quickly established that the hypothalamus is the referred to as a releasing hormone. In contrast, each hor- regulator of the anterior pituitary, but how the hypothala- mone thought to inhibit the release of an anterior pituitary mus carries out this role remained a mystery. You see, the hormone was referred to as a release-inhibiting hormone. anterior pituitary, unlike the posterior pituitary, receives no Efforts to isolate the putative (hypothesized) hypotha- neural input whatsoever from the hypothalamus, or from lamic releasing and release-inhibiting hormones led to a major any other neural structure (see Figure 13.3). breakthrough in the late 1960s. Guillemin and his colleagues CONTROL OF THE ANTERIOR AND POSTERIOR isolated thyrotropin-releasing hormone from the hypothal- PITUITARY BY THE HYPOTHALAMUS. There are two amus of sheep, and Schally and his colleagues isolated the different mechanisms by which the hypothalamus controls same hormone from the hypothalamus of pigs. Thyrotropin- the pituitary: one for the posterior pituitary and one for the releasing hormone triggers the release of thyrotropin from anterior pituitary. The two major hormones of the posterior the anterior pituitary, which in turn stimulates the release of pituitary, vasopressin and oxytocin, are peptide hormones hormones from the thyroid gland. For their efforts, Guillemin that are synthesized in the cell bodies of neurons in the and Schally were awarded Nobel Prizes in 1977. paraventricular nuclei and supraoptic nuclei on each side Schally’s and Guillemin’s isolation of thyrotropin- of the hypothalamus (see Figure 13.3 and Appendix VI). releasing hormone confirmed that hypothalamic releasing M13_PINE1933_11_GE_C13.indd 349 22/01/2021 11:25  350 Chapter 13 Figure 13.4 Control of the anterior and posterior pituitary by the hypothalamus. Paraventricular Anterior Pituitary Posterior Pituitary nucleus 1 Releasing and inhibiting hormones are released from hypothalamic neurons Supraoptic nucleus 1 Oxytocin and vasopressin are synthesized in the paraventricular and supraoptic into the hypothalamo- nuclei of the hypothalamus. pituitary portal system. 2 Hypothalamic-releasing and hypothalamic-inhibiting hormones are carried down 2 Oxytocin and vasopressin are carried by axonal the pituitary stalk by the transport down the pituitary hypothalamopituitary portal stalk. system. 3 Hypothalamic-releasing and hypothalamic-inhibiting hormones increase or 3 Oxytocin and vasopressin are released into general circulation from terminal buttons decrease, respectively, the in the posterior pituitary. release of anterior pituitary hormones into general circulation. Posterior Anterior pituitary pituitary hormones control the release of hormones from the anterior Endocrine glands located in the brain (i.e., the pituitary pituitary and thus provided the major impetus for the and pineal glands) are regulated by cerebral neurons. In isolation and synthesis of other releasing and release- contrast, those endocrine glands located outside the CNS inhibiting hormones. Of direct relevance to the study of sex are innervated by the autonomic nervous system—usually by hormones was the subsequent isolation of gonadotropin- both the sympathetic and parasympathetic branches, which releasing hormone by Schally and his group (Schally, often have opposite effects on hormone release. Kastin, & Arimura, 1971). This releasing hormone stimulates It is extremely important to remember that hormone the release of both of the anterior pituitary’s gonadotropins: release can be influenced by experience—for example, many follicle-stimulating hormone (FSH) and luteinizing species that breed only in the spring are often prepared for hormone (LH). All hypothalamic-releasing hormones, like reproduction by the release of sex hormones triggered by all tropic hormones, have proven to be peptides. the increasing daily duration of daylight. This means that an explanation of any behavioral phenomenon in terms of Regulation of Hormone Levels a hormonal mechanism does not necessarily rule out an explanation in terms of an experiential mechanism. LO 13.6 Describe three different types of signals that regulate hormone release. Also, describe how Journal Prompt 13.1 hormones are released over time and the Given what you have just learned about the hormonal effect this pattern of release has on levels of differences between males and females, comment circulating hormones. on the following statement: “Men are from Mars and women are from Venus.” Hormone release is regulated by three different kinds of signals: signals from the nervous system, signals from circu- REGULATION BY HORMONAL SIGNALS. The hor- lating hormones, and signals from circulating nonhormonal mones themselves also influence hormone release. You have chemicals. already learned, for example, that the tropic hormones of REGULATION BY NEURAL SIGNALS. All endocrine the anterior pituitary influence the release of hormones glands, with the exception of the anterior pituitary, are from their respective target glands. However, the regula- directly regulated by signals from the nervous system. tion of endocrine function by the anterior pituitary is not a M13_PINE1933_11_GE_C13.indd 350 22/01/2021 11:25  Hormones and Sex 351 one-way street. Circulating hormones often provide Figure 13.5 A summary model of the regulation of gonadal hormones. feedback to the very structures that influence their release: the pituitary gland, the hypothalamus, and other sites in the brain. The function of most hor- BRAIN monal feedback is the maintenance of stable blood neural signals levels of the hormones. Thus, high gonadal hormone levels usually have effects on the hypothalamus and pituitary that decrease subsequent gonadal hormone HYPOTHALAMUS releases gonadotropin- release, and low levels usually have effects that releasing hormone increase hormone release. Behavior is HYPOTHALAMOPITUITARY influenced REGULATION BY NONHORMONAL CHEMICALS. PORTAL SYSTEM by gonadal hormones Circulating chemicals other than hormones can play acting on a role in regulating hormone levels. Glucose, c­ alcium, the brain. and sodium levels in the blood all influence the release ANTERIOR PITUITARY releases gonadotropin of particular hormones. For example, you learned in ­Chapter 12 that increases in blood glucose increase Positive or the release of insulin from the pancreas; in turn, insulin GENERAL negative reduces blood glucose levels. CIRCULATION feedback influences the subsequent PULSATILE HORMONE RELEASE. Hormones release of tend to be released in pulses (see Plant, 2015); they hormones. are discharged several times per day in large surges, GONADS release estrogens, which typically last no more than a few minutes. androgens, and Hormone levels in the blood are regulated by changes progestins in the frequency and duration of the hormone pulses. One consequence of pulsatile hormone release is that there are often large minute-to-minute fluctuations in the levels of circulating hormones (see Lightman & Conway-Campbell, 2010). Accordingly, when the pattern of human male gonadal hormone release is BODY TISSUES referred to as “steady,” it means that there are no major systematic changes in circulating gonadal hormone levels from day to day, not that the levels never vary. Summary Model of Gonadal Endocrine Regulation Hormones and Sexual LO 13.7 Summarize the model of gonadal endocrine Development of the Body regulation. You have undoubtedly noticed that humans are dimorphic— Figure 13.5 is a summary model of the regulation of gonadal that is, most come in one of two models: female and hormones. According to this model, the brain controls male. This module describes how the development of female the release of gonadotropin-releasing hormone from the and male bodily characteristics is directed by hormones. ­hypothalamus into the hypothalamopituitary portal system, which carries it to the anterior pituitary. In the anterior Sexual Differentiation ­pituitary, the gonadotropin-releasing hormone stimulates the LO 13.8 Describe the development of the internal and release of gonadotropins, which are carried by the circulatory external reproductive organs. system to the gonads. In response to the gonadotropins, the gonads release androgens, estrogens, and progestins, which Sexual differentiation in mammals begins at fertilization feed back into the pituitary and hypothalamus to regulate with the production of one of two different kinds of zygotes: subsequent gonadal hormone release. Armed with this either one with an XX (female) pair of sex chromosomes general perspective of neuroendocrine function, you are or one with an XY (male) pair. It is the genetic information now ready to consider how gonadal hormones direct sexual on the sex chromosomes that usually determines whether development and activate adult sexual behavior. development will occur along female or male lines. But be M13_PINE1933_11_GE_C13.indd 351 22/01/2021 11:25  352 Chapter 13 cautious here: Do not fall into the seductive embrace of the block the effects of Sry protein are injected into a genetic male men-are-men-and-women-are-women assumption. Do not fetus, the result is a genetic male with ovaries. Such exam- begin by assuming that there are two parallel but opposite ples of intersexed persons expose in a dramatic fashion the genetic programs for sexual development, one for female weakness of mamawawa thinking (thinking of “male” and development and one for male development. As you are “female” as mutually exclusive, opposite categories). about to learn, sexual development is far more complex. INTERNAL REPRODUCTIVE DUCTS. Six weeks after fer- FETAL HORMONES AND DEVELOPMENT OF REPRO- tilization, all fetuses have two complete sets of reproductive DUCTIVE ORGANS. Figure 13.6 illustrates the structure ducts. They have a Wolffian system, which has the capacity to of the gonads as they appear 6 weeks after fertilization. develop into male reproductive ducts (e.g., the seminal ­vesicles, Notice that at this stage of development, each fetus, regard- which hold the fluid in which sperm cells are ejaculated; and less of its genetic sex, has the same pair of gonadal struc- the vas deferens, through which the sperm cells travel to the tures, called primordial gonads (primordial means “existing at seminal vesicles). And they have a Müllerian system, which the beginning”). Each primordial gonad has an outer cov- has the capacity to develop into female ducts (e.g., the uterus; ering, or cortex, which has the potential to develop into an the upper part of the vagina; and the fallopian tubes, through ovary; and each has an internal core, or medulla, which has which ova travel from the ovaries to the uterus). the potential to develop into a testis. In the third month of male fetal development, the testes In the seventh week after conception, the Sry gene on the secrete testosterone and Müllerian-inhibiting substance. Y chromosome of a male triggers the synthesis of Sry protein As Figure 13.7 illustrates, the testosterone stimulates the (see Arnold, 2017; Sekido & Lovell-Badge, 2013; Wu et al., 2012), and this protein causes the medulla of each ­primordial gonad to grow and to develop into a testis. In the absence Figure 13.7 The development of the internal ducts of the of Sry protein, the cortical cells of the primordial gonads male and female reproductive systems from the Wolffian and Müllerian systems, respectively. develop into ovaries (see Lin & Capel, 2015). So, if Sry protein is injected into a genetic female fetus 6 weeks after concep- At 6 weeks, all human fetuses have the tion, the result is a genetic female with testes; or if drugs that antecedents of both male (Wolffian) and female (Müllerian) reproductive ducts. Figure 13.6 The development of an ovary and a testis from the cortex and the medulla, respectively, of the primordial gonadal structure that is present 6 weeks after conception. Wolffian system Developing At 6 weeks after conception, the primordial gonad Müllerian gonads of XX and XY individuals are identical. system Medulla of the primordial Male (XY) Female (XX) gonad Cortex of the Seminal Fallopian primordial vesicle tube gonad Female (XX) Male (XY) Vas Uterus Ovary deferens Upper part of vagina Testis Scrotum Under the influence of In the absence of testicular testosterone, the testosterone, the Müllerian Wolffian system develops, system develops into If no Sry protein is Under the influence of and Müllerian-inhibiting female reproductive ducts, present, the cortex of Sry protein, the medulla substance causes the and the Wolffian system the primordial gonad of the primordial gonad Müllerian system to fails to develop. develops into an ovary. develops into a testis. degenerate. M13_PINE1933_11_GE_C13.indd 352 22/01/2021 11:25  Hormones and Sex 353 development of the Wolffian system, and the Figure 13.8 The development of male and female external reproductive Müllerian-inhibiting substance causes the organs from the same bipotential precursor. Müllerian system to degenerate and the testes to descend into the scrotum—the ball sac that Six Weeks After holds the testes outside the body cavity (see Conception Bipotential Sajjad, 2010). Because it is testosterone—not Precursor Glans the sex chromosomes—that triggers Wolffian development, genetic females who are injected Urethral fold with testosterone during the appropriate fetal Lateral body period develop male reproductive ducts along Labioscrotal swelling with their female ones. The differentiation of the internal ducts of the female reproductive system (see Figure 13.7) is not under the control of ovarian Partially hormones; the ovaries are almost completely Developed inactive during fetal development. The development of the Müllerian system occurs Male Female in any fetus that is not exposed to testicular hormones during the critical fetal period. Accordingly, female fetuses, ovariectomized female fetuses, and orchidectomized male fetuses all develop female reproductive ducts (Jost, 1972). Ovariectomy is the removal of the ovaries, and orchidectomy is the removal of the testes (the Greek word orchis means “testicle”). Fully Gonadectomy, or castration, is the surgical Developed removal of gonads—either ovaries or testes. Clitoral hood Head of penis Male Female Clitoris EXTERNAL REPRODUCTIVE ORGANS. Labia minora There is a basic difference between the differentiation of the external reproductive Shaft of penis organs and the differentiation of the internal reproductive organs (i.e., the gonads and Scrotum Labia majora reproductive ducts). Anus Anus As you have just read, every typical fetus develops separate precursors for the male (medulla) and female (cortex) gonads and for the male (Wolffian system) and female by the presence or absence of testosterone. If testosterone is (Müllerian system) reproductive ducts; then, only one set, present at the appropriate stage of fetal development, male male or female, develops. In contrast, both male and female external genitals develop from the bipotential precursor. genitals develop from the very same precursor (see Sajjad, Conversely, if testosterone is not present, development 2010). This bipotential precursor and its subsequent differen- of the external genitals proceeds along female lines tiation are illustrated in Figure 13.8. (see Matsushita et al., 2018). At the end of the third month of pregnancy, the bipoten- tial precursor of the external reproductive organs consists of four parts: the glans, the urethral folds, the lateral bodies, Puberty: Hormones and and the labioscrotal swellings. Then it begins to differenti- Development of Secondary Sex ate. The glans grows into the head of the penis in the male or Characteristics the clitoris in the female; the urethral folds fuse in the male or enlarge to become the labia minora in the female; the lateral LO 13.9 Describe the male and female secondary sex bodies form the shaft of the penis in the male or the hood of characteristics and the role of hormones in their the clitoris in the female; and the labioscrotal swellings form development. the scrotum in the male or the labia majora in the female. During childhood, levels of circulating gonadal hormones Like the development of the internal reproductive are low, reproductive organs are immature, and males and ducts, the development of the external genitals is controlled females differ little in general appearance. This period M13_PINE1933_11_GE_C13.indd 353 22/01/2021 11:25  354 Chapter 13 of developmental quiescence Figure 13.9 The changes that typically occur in males and females during puberty. ends abruptly with the onset of puberty—the transitional period between childhood and Hair line Acne appears adulthood during which fertility recession begins is achieved, the adolescent Acne appears Larynx enlarges Facial and body growth spurt occurs, and the hair appears secondary sex characteristics Musculature develop. Secondary sex develops Breasts characteristics are those features Axillary hair Axillary hair develop other than the reproductive appears appears organs that distinguish sexually Body Pubic hair contours mature males and females. appears Menstruation become Many of these secondary sex begins rounded Reproductive characteristics develop during organs grow Uterus puberty (see Figure 13.9). grows Puberty is associated with an increase in the release of hormones Growth spurt Pubic hair Growth spurt occurs appears occurs by the anterior pituitary. The increase in the release of growth hormone—the only anterior pituitary hormone that does not have a gland as its primary target—acts directly on bone and muscle tissue to produce the pubertal growth spurt (see Colvin & Abdullatif, 2013; Russell et al., 2011). Increases in the release of gonadotropic hormone and adrenocorticotropic hormone cause the gonads and adrenal cortex to increase their release of gonadal and adrenal hormones, which in turn initiate the maturation of the genitals and the development of Sexual Development of secondary sex characteristics. The general principle guiding typical pubertal sexual Brain and Behavior maturation is a simple one: In pubertal males, androgen As you have just learned, the principles of the differentia- levels are higher than estrogen levels, and masculinization tion of the human body are well understood. But now, is the result; in pubertal females, the estrogens predomi- current research is focusing on a more difficult problem, nate, and the result is feminization (see Colvin & Abdullatif, the sexual differentiation of brain and behavior. This mod- 2013). Individuals castrated prior to puberty do not become ule reveals how seminal studies conducted in the 1930s sexually mature unless they receive replacement injections generated theories that have morphed, under the influ- of androgens or estrogens. ence of subsequent research, into our current views. But even during puberty, the men-are-men-and- Sex differences in brain and behavior has been the women-are-women assumption stumbles badly. You see, identification of a systematic problem in neuroscience androstenedione, an androgen that is released primarily by research. Until recently, male-only studies or studies the adrenal cortex, is typically responsible for the growth of where both males and females were lumped together as pubic hair and axillary hair (underarm hair) in females. It is one group were the norm (see Fischer & Riddle, 2018). hard to take seriously the practice of referring to androgens However, because of the growing body of research on as “male hormones” when one of them is responsible for sex-related brain differences, this practice is changing (see the development of the female pattern of pubic hair growth. Choleris et al., 2018). Indeed, many funding agencies now The male pattern is a pyramid, and the female pattern is an require that their researchers always assess for potential inverted pyramid (see Figure 13.9). sex differences in brain and behavior. M13_PINE1933_11_GE_C13.indd 354 22/01/2021 11:25  Hormones and Sex 355 Sex Differences in the Brain pattern of gonadotropin release from the hypothalamus and initiating the development of the steady male pattern. This LO 13.10 Describe the evolution of research and 1960s modification of Pfeiffer’s theory of brain differentiation thinking about to include the hypothalamus was consistent with the facts sex differences in the brain. of brain differentiation as understood at that time, but The brains of males and females may look the same on subsequent research necessitated major revisions. The first casual inspection, and it may be politically correct to believe of these major revisions became known as the aromatization that they are—but they are not. The brains of males tend to hypothesis. be about 15 percent larger than those of females on average, and many other anatomical differences between male and AROMATIZATION HYPOTHESIS. What is aromatiza- female brains have been documented. There are differences tion? All gonadal and adrenal sex hormones are steroid in the average volumes of various cortical areas, nuclei and ­hormones, and because all steroid hormones are derived fiber tracts, in the numbers and types of neural and glial from cholesterol, they have similar structures and are read- cells that compose various structures, in the plasticity of ily converted from one to the other. For example, a slight ­certain brain structures, and in the numbers and types change to the testosterone molecule that occurs under of synapses that connect the cells in various structures the influence of the enzyme (a protein that influences a (see Brecht, Lenschow, & Rao, 2018; Choleris et al., 2018; ­biochemical reaction without participating in it) aromatase Grabowska, 2017; Hausmann, 2017; McCarthy, Nugent, & converts testosterone to estradiol. This process is called Lenz, 2017; Mottron et al., 2015). aromatization. Let’s begin with the first functional sex difference to be According to the aromatization hypothesis, perinatal identified in mammalian brains. testosterone does not directly masculinize the brain; the brain is masculinized by estradiol that has been aromatized from FIRST DISCOVERY OF A SEX DIFFERENCE IN MAMMA- perinatal testosterone. Although the idea that estradiol— LIAN BRAIN FUNCTION. The first attempts to discover the alleged female hormone—masculinizes the brain may sex differences in the mammalian brain focused on the fac- seem counterintuitive, there is strong evidence for it in rats tors that control the development of the steady and cyclic and mice: (1) findings demonstrating masculinizing effects patterns of gonadotropin release in males and females, on the brain of early estradiol injections, and (2) findings respectively. The seminal experiments were conducted showing masculinization of the brain does not occur in by Pfeiffer in 1936. In his experiments, some neonatal rats response to testosterone administered with agents that (males and females) were gonadectomized and some were block aromatization or in response to androgens that cannot not, and some received gonad transplants (ovaries or testes) be aromatized (e.g., dihydrotestosterone). and some did not. How do genetic females of species whose brains are Remarkably, Pfeiffer found that gonadectomizing masculinized by estradiol keep from being masculin- neonatal rats of either genetic sex caused them to develop ized by their mothers’ estradiol, which circulates through into adults with the female cyclic pattern of gonadotropin the fetal blood supply? Alpha fetoprotein is the answer. release. In contrast, transplantation of testes into gonad- Alpha fetoprotein is present in the blood of rodents during ectomized or intact female neonatal rats caused them to the perinatal period, and it deactivates circulating estradiol develop into adults with the steady male pattern of gonad- by binding to it (see Yang & Shah, 2014). Although the role otropin release. Transplantation of ovaries had no effect of alpha fetoprotein in deactivating estradiol is firmly estab- on the pattern of hormone release. Pfeiffer concluded that lished in rodents, its function in humans remains controver- the female cyclic pattern of gonadotropin release develops sial (see Koebele & Bimonte-Nelson, 2015). unless the preprogrammed female cyclicity is overridden How, then, does estradiol masculinize the brain of the by testosterone during perinatal development. male rodent fetus in the presence of the deactivating effects Pfeiffer incorrectly concluded that the presence or of alpha fetoprotein? Because testosterone is immune to absence of testicular hormones in neonatal rats influenced alpha fetoprotein, it can travel unaffected from the testes to the development of the pituitary because he was not the brain cells where it is converted to estradiol. Estradiol aware of something we know today: The release of is not broken down in the rodent brain because alpha feto- gonadotropins from the anterior pituitary is controlled by protein does not readily penetrate the blood–brain barrier. the hypothalamus. Once this was discovered, it became How does the aromatization hypothesis fare when it apparent that Pfeiffer’s experiments had provided the first comes to explaining human masculinization? The aroma- evidence of the role of perinatal (around the time of birth) tization hypothesis was initially considered generalizable androgens in overriding the preprogrammed cyclic female to humans. However, current research tells us that any M13_PINE1933_11_GE_C13.indd 355 22/01/2021 11:25  356 Chapter 13 masculinizing effects of testosterone are due to its direct effects (see de Bournonville et al., 2019; Lentini et al., 2012). effects on the human brain (see Motta-Mena & Puts, 2017; Also, some sex differences in the brain are not manifested Puts & Motta-Mena, 2018). until puberty, and these differences are unlikely to be the product of perinatal hormones (see Ingalhalikar et al., SEX DIFFERENCES IN THE BRAIN: THE MODERN 2014), which, as you have just learned, play a role in the PERSPECTIVE. So far, our discussion of the development development of some sex differences in the brain. of sex differences has focused on the reproductive organs, Further complicating the study of the development of sex secondary sex characteristics, and the hypothalamus. You differences in the brain is the fact that three factors that have have learned from this discussion that one theory accounts proven to play little or no role in the sexual differentiation of the for the development of many sex differences: The default reproductive organs do play a role in the sexual differentiation program of development is the female program, which is of the brain. First, sex chromosomes have been found to overridden in genetic males by perinatal exposure to tes- influence brain development independent of their effect on tosterone. The initial assumption was that this same mecha- hormones (see Arnold, 2017; Khramtsova et al., 2019; Maekawa nism would prove to be the sole mechanism responsible et al., 2014); for example, different patterns of gene expression for the development of other differences between male and (see Chapter 2) exist in the brains of male and female mice female brains. However, this has not proven to be the case even before the gonads become functional (e.g., Wolstenholme, (see Arnold, 2017; Lenz, Nugent, & McCarthy, 2012). Rissman, & Bekiranov, 2013). Second, epigenetic effects Before considering the mechanisms by which influence the emergence of brain sex differences. For example, sex differences in the brain develop, it is important to epigenetic mechanisms (see Chapter 2) can interact with understand the nature of the differences. The vast majority gonadal hormones to produce sex-specific effects on brain of sex differences in the brain are not all-or-none, men-are- development (see Forger, 2018; McCarthy, Nugent, & Lenz, men-and-women-are-women differences. Most of the sex 2017). Third, although the female program of reproductive differences in the brain that have been documented are organ development typically proceeds in the absence of slight, variable, and statistical. In short, many differences gonadal steroids, recent evidence suggests that estradiol plays exist between average male and female brains, but there an active role; knockout mice without the gene that forms is usually plenty of overlap. Indeed, in humans there is so estradiol receptors do not display a female pattern of brain much overlap that some researchers have argued it would development (see Maekawa et al., 2014). Thus, although the be better for us not to think in terms of male brains versus conventional view that a female program of development is the female brains (see Joel & Fausto-Sterling, 2016). default program does a good job of explaining differentiation At the same time, it would be a big mistake to ignore the of the reproductive organs and hypothalamus, it falters badly study of differences between the brains of men and women. when it comes to differentiation of the brain in general. Even if most documented differences are slight, variable, The mechanisms of brain differentiation appear to and statistical, collectively those differences are sufficient to be much more complex and selective. Complicating their have significant health implications for the ­different sexes study is the fact that these complex mechanisms are differ- (see Ball, Balthazart, & McCarthy, 2014; C ­ holeris et al., 2018; ent in different mammalian species (see Sekido, 2014). For Geary, 2019). For example, there are marked sex differences example, as discussed earlier, although aromatization plays in the incidence of neurological disorders: P ­ arkinson’s a role in the masculinization of the brains of rats and mice, ­disease and autism spectrum disorder are far more ­common it doesn’t in humans. in males, whereas Alzheimer’s disease is far more com- mon in females (see Gurvich et al., 2018). Of major clinical relevance is the discovery that males do not recover from Development of Sex Differences traumatic brain injury as well as females (see M ­ ollayeva, in Behavior Mollayeva, & Colantonio, 2018). LO 13.11 Describe the results of studies of sex Although research on the development of sex differences differences in behavior in humans and in the brain is still in its infancy, one important principle nonhumans. has emerged. Brains are not masculinized or feminized as a whole: Sex differences develop independently in different Because it is not ethical to conduct experiments on the parts of the brain at different points in time and by different development of sex differences in humans, most of the mechanisms (see Joel & Fausto-Sterling, 2016). For example, research on this topic has focused on the development aromatase is found in only a few areas of the rat brain of reproductive behavior in laboratory animals. Until (e.g., the hypothalamus), and it is only in these areas that recently, this research has focused on the effects of peri- aromatization is critical for testosterone’s masculinizing natal hormones. M13_PINE1933_11_GE_C13.indd 356 22/01/2021 11:25  Hormones and Sex 357 DEVELOPMENT OF REPRODUCTIVE BEHAVIORS IN demasculinization. If you think that masculinization and LABORATORY ANIMALS. Phoenix and colleagues (1959) defeminization are the same thing and that feminization were among the first to demonstrate that the perinatal and demasculinization are the same thing, you have likely injection of testosterone masculinizes and defeminizes a fallen into the trap of the men-are-men-and-women-are- genetic female’s adult reproductive behavior. First, they women assumption—that is, into the trap of thinking of injected pregnant guinea pigs with testosterone. Then, when maleness and femaleness as discrete, mutually exclusive, the litters were born, the researchers ovariectomized the opposite categories. Indeed, male behaviors and female female offspring. Finally, when these ovariectomized female behaviors can coexist in the same individual, and they guinea pigs reached maturity, the researchers injected them do not necessarily change in opposite directions if the with testosterone and assessed their copulatory behavior. individual receives physiological treatment such as Phoenix and his colleagues found that the females exposed hormones or brain lesions. For example, “male” behaviors to perinatal testosterone displayed more male-like mounting (e.g., mounting receptive females) have been observed in behavior in response to testosterone injections in adulthood the females of many different mammalian species, and than adult females who had not been exposed to perinatal “female” behaviors (e.g., lordosis) have been observed testosterone. And when as adults the female guinea pigs in males (see Reznikov et al., 2016). Furthermore, lesions were injected with progesterone and estradiol and mounted in medial preoptic areas have been shown to abolish by males, they displayed less lordosis (the intromission- male reproductive behaviors in both male and female facilitating arched-back posture that signals female rats without affecting female behaviors (see Singer, rodent receptivity). 1968; Will, Hull, & Dominguez, 2014). Think about this In a study complementary to that of Phoenix and idea carefully; it plays an important role in later parts of colleagues, Grady, Phoenix, and Young (1965) found that the chapter. the lack of early exposure of male rats to testosterone both feminizes and demasculinizes their reproductive behavior DEVELOPMENT OF SEX DIFFERENCES IN THE BEHAV- as adults. Male rats castrated shortly after birth failed to IOR OF HUMANS. There is much research on the devel- display the typical male copulatory pattern of mounting, opment of behavioral differences in human females and intromission (penis insertion), and ejaculation (ejection of males. However, because experimental investigations of sperm) when as adults they were treated with testosterone this process are not ethical, virtually all of the research is and given access to a sexually receptive female. Moreover, based on case studies and correlational studies, which are when they were injected with estrogen and progesterone difficult to interpret (see Chapter 1). Still, three general con- as adults, they exhibited more lordosis than uncastrated clusions have emerged. controls. First, some sex differences in human behavior appear When it comes to the effects of perinatal testosterone on to be sexual dimorphisms (see McCarthy et al., 2012; rat reproductive behavior development, timing is critical. Rigby & Kulathinal, 2015; Yang & Shaw, 2014). Sexual The ability of single injections of testosterone to masculinize dimorphisms are instances where a behavior (or a struc- and defeminize rat reproductive behavior seems to be ture) typically comes in two distinctive classes (male or restricted to the first 5 days after birth (see McCarthy, female) into which most individuals can be unambigu- Herold, & Stockman, 2018). ously assigned. In the case of humans, it appears to be Because much of the research on hormones and the only reproduction-related behaviors that clearly fall into development of reproductive behavior has focused on the this category. The presence or absence of prenatal testos- copulatory act, we know less about the role of hormones terone appears to be a major factor in the development of in the development of proceptive behaviors (solicitation these behaviors (see Balthazart, 2011; Kreukels & Cohen- behaviors) and in the development of sex-related behaviors Kettenis, 2012). that are not directly related to reproduction. However, Second, most differences between the behavior of aver- perinatal testosterone has been found to disrupt the age human males and average human females are small and proceptive hopping, darting, and ear wiggling of receptive characterized by substantial overlap between individuals female rats. of the two groups (see Hines, 2011; McCarthy et al., 2012; Before you finish this section, we want to clarify an Miller & Halpern, 2014). For example, such human behav- important point. If you are like many of our students, ioral sex differences occur in play behavior, social interac- you may be wondering why biopsychologists who study tion, reaction to pain, language, cognition, emotionality, drug the development of male–female behavioral differences sensitivity, and responses to stress (see Bale & ­Epperson, always measure masculinization separately from 2015; Eisenegger, Haushofer, & Fehr, 2011; Loyd & Murphy, defeminization and measure feminization separately from 2014; Miller & Halpern, 2014; Mogil, 2012). The presence or M13_PINE1933_11_GE_C13.indd 357 22/01/2021 11:25  358 Chapter 13 absence of prenatal testosterone exposure has been shown depression, anxiety disorders, and Alzheimer’s disease; and to contribute to the development of these kinds of sex about 10 times as many females are diagnosed with certain differences, but in general they account for only a portion eating disorders. The mechanisms leading to the develop­ of each difference. ment of any of these sex differences in susceptibility to The third conclusion that has emerged from the study behavioral disorders is unclear (see Cahill, 2014; ter Horst of human behavioral sex differences is that there are often et al., 2012). differences in the susceptibility of human males and females Before leaving the topic of sex differences in brain to behavioral disorders (see McCarthy et al., 2012; ter Horst and behavior, we want to emphasize that the frequent et al., 2012; Zhao, Woody, & Chhibber, 2015). For example, finding that prenatal testosterone exposure influences the dyslexia (reading difficulties), early-onset schizophrenia, development of sex differences does not preclude other stuttering, and autism spectrum disorders are each about factors (see Hines, 2011). For example, cultural factors have three times more prevalent in males; and attention deficit been shown to play a major role in the development of hyperactivity disorder is 10 times more likely in males. many sex differences, perhaps by acting on the same brain In contrast, females are twice as likely to be diagnosed with mechanisms influenced by prenatal hormones. Scan Your Brain Before you proceed to a consideration of three cases of 5. The scrotum and the _______ develop from the same exceptional human sexual development, scan your brain bipotential precursor. to see whether you understand the basics of typical sexual 6. In rodents, the presence of _______ in the prenatal period development. Fill in the blanks in the following sentences. The blocks the circulation of estradiol by binding to it. correct answers are provided at the end of the exercise. Review 7. _______ chromosomes have been found to influence material related to your errors and omissions before proceeding. brain development independent of their effect on hormones. 1. Under the influence of _______ protein, the medulla 8. _______ are instances where a behavior (or structure) develops into a testis. comes in two distinct classes (male or female) into which 2. The increase in the release of _______ hormone acts most individuals can be unambiguously assigned. directly on bone and muscle tissue to produce the 9. Certain conditions such as early-onset schizophrenia, ­pubertal growth spurt. autism spectrum disorders, stuttering, and _______ are 3. Increases in the release of _______ hormone and _______ three times more prevalent in males. hormone cause the gonads and adrenal cortex to increase their release of gonadal and adrenal hormones, which in turn initiate the maturation of the genitals and the development of secondary sex characteristics. 4. The hormonal factor that triggers the development of the (6) alpha fetoprotein, (7) Sex, (8) Sexual dimorphisms, (9) dyslexia. human Müllerian system is the lack of _______ around the adrenocorticotropic, (4) androgens (or testosterone), (5) labia majora, third month of fetal development. Scan Your Brain answers: (1) Sry, (2) growth, (3) gonadotropic, a proverb: The exception proves the rule. Most people Three Cases of Exceptional think this proverb means that the exception “proves” the rule in the sense that it establishes its truth, but this is Human Sexual clearly wrong: The truth of a rule is challenged by, not Development confirmed by, exceptions to it. The word proof in this usage comes from the Latin probare, which means “to This module discusses three cases of exceptional sexual test”—as in proving ground—and this is the sense in which development. We are sure you will be intrigued by these it is used in the proverb. Hence, the proverb means that three cases, but that is not the only reason we have the explanation of exceptional cases is a testing ground chosen to present them. Our main reason is expressed by for any theory. M13_PINE1933_11_GE_C13.indd 358 22/01/2021 11:25  Hormones and Sex 359 Exceptional Cases of Human Sexual because of her unresponsive androgen receptors; thus, her development proceeded as if no androgens had been released. Development Her external genitals, her brain, and her behavior developed LO 13.12 Explain what androgen insensitivity along female lines, without the effects of androgens to syndrome, adrenogenital syndrome, and override the female program, and her testes could not ablatio penis have taught us about human descend from her body cavity with no scrotum for them to sexual development. descend into. Furthermore, Anne did not develop typical internal female reproductive ducts because, like other genetic So far in this chapter, you have learned the rules according males, her testes released Müllerian-inhibiting substance; that to which hormones seem to influence typical sexual devel- is why her vagina was short and her uterus underdeveloped. opment. Now, three exceptional cases are offered to prove At puberty, Anne’s testes released enough estrogens to (to test) these rules. feminize her body in the absence of the counteracting effects of androgens; however, adrenal androstenedione was not able to stimulate the growth of pubic and axillary hair. The Case of Anne S., the Woman An interesting issue of medical ethics is raised by the with Testes androgen insensitivity syndrome. Many people believe that physicians should always disclose all relevant findings to Anne S., a 26-year-old female, sought treatment for two their patients. If you were Anne’s physician, would you tell sex-related disorders: lack of menstruation and pain dur- her that she is a genetic male? Would you tell her husband? ing sexual intercourse (Jones & Park, 1971). She sought help