Puberty and Male Development Quiz

Reproductive Hormones

• Reproductive hormones affect all aspects of reproductive function, including growth during puberty and aging.
• Outcomes include outlining the synthesis, metabolism, regulation of secretion of sex hormones.
• Describing the mechanism of actions and effects of sex hormones during puberty and in adults.
• Describing the hormonal basis of ovular and anovular menstrual cycles and signs of ovulation.
• Discussing the manipulation of menstrual cycles (e.g., contraceptives).
• Describing the effects of 5α-reductase deficiency, orchidectomy (before and after puberty), and congenital adrenal hyperplasia.

Synthesis: Estrogens

• Cholesterol is the basic ingredient for all steroid hormones.
• Estrogens (estradiol, estrone, estriol) are synthesized in the ovaries.
• The process involves several enzymatic steps, starting with cholesterol, transforming into pregnenolone and other intermediates.
• Aromatase is a key enzyme converting androstenedione into estrogens.
• Theca cells produce androgens, and further converted to estrogens by granulosa cells.
• Estrogens circulate in the blood.

Metabolism and excretion

• The primary site for metabolism is the liver.
• Estrogens are converted to glucuronide and sulfate conjugates.
• Metabolites and conjugates are subsequently excreted in the urine.
• Some amounts are secreted in the bile and reabsorbed into the bloodstream (enterohepatic circulation).

Actions of Estrogens

• Estrogens lead to the development of secondary sex characteristics in women.
• These include changes in body proportions (wide hips, narrow shoulders), distribution of fat deposits (breasts, buttocks), development of the larynx retaining its prepubertal proportions (high-pitched voice).
• Estrogens also contribute to the growth of pubic and axillary hair.
• Estrogens affect the female reproductive tract; proliferation of endometrium, uterine glands lengthen, makes cervical mucus thinner and more alkaline to promote sperm survival and transport.
• Cervical mucus has a fern-like pattern. Vaginal epithelium becomes cornified.
• Other impacts include the proliferation of mammary ducts, facilitate the growth of ovarian follicles, and increase the motility of uterine tubes, and increase uterine blood flow.
• These influence the content of contractile proteins in uterine muscle and sensitizes the uterus to oxytocin.
• Estrogens also contribute to bone density, blood cholesterol levels.

Synthesis: Progesterone

• Progesterone is synthesized from cholesterol, via pregnenolone as an intermediate.
• The synthesis mainly occurs in the corpus luteum and placenta during pregnancy.
• Progesterone is crucial for maintaining pregnancy.
• Progesterone influences the uterus and affects the endometrium, breasts, and brain, thus influencing female behavior patterns.

Secretion, Transport and Metabolism: Progesterone

• Secretion sites include the corpus luteum, placenta and in small amounts the follicle; 80% bound to albumin and 18% to corticosteroid binding globulin.
• The main target organs are uterus, breasts, and brain.
• Progesterone influences endometrium to maintain the secretory phase, increases uterine glands tortuosity, spiral arteries tortuosity, and secretion of glands.
• Thickens cervical mucus and inhibits the ferning caused by estrogen.
• The epithelium proliferates and becomes infiltrated with leukocytes (vagina).

Effects of Progesterone

• Antiestrogen effect, decreasing myometrial excitability, sensitivity to oxytocin, and spontaneous electrical activity.
• Decreases estrogen receptors in endometrium and increases conversion of estrogen to less active forms.
• Growth of lobules and alveoli in the breast.
• Large doses of progesterone inhibit LH secretion and potentiate the effects of estrogen, thus preventing ovulation.
• Progesterone is thermogenic, potentially influencing the rise in basal body temperature during ovulation.
• Prominent in respiratory and alveolar PCO2 regulation during pregnancy.

Mechanism of actions

• Estrogen receptors (ERα and ERβ), primarily with genomic effects, but also some rapid non-genomic effects.
• Progesterone works via action on DNA, new mRNA synthesis. Progesterone receptor binds to a heat shock protein in the absence of progesterone.
• Progesterone binding releases the heat shock protein, unveiling the DNA-binding domain of the receptor.
• Two isoforms of the progesterone receptor exist: PRA and PRB.

Regulation or Ovarian Hormone Secretion

• Regulation of ovarian secretion depends on the hypothalamic-pituitary-gonadal (HPG) axis.
• GnRH from the hypothalamus stimulates the anterior pituitary to release LH and FSH.
• Ovaries produce inhibin B to negatively regulate FSH release.
• Estrogen and progesterone have negative feedback loops to regulate LH and FSH.
• These regulatory mechanisms control the menstrual cycle.

Synthesis of Male Reproductive Hormones

• Testosterone is the principle hormone synthesized in the testes, from cholesterol via intermediates such as pregnenolone, progesterone and others.
• The location of synthesis is primarily Leydig cells.
• Androstenedione is another source of testosterone.
• In some target tissues, androstenedione is converted to dihydrotestosterone.

Metabolism

• Most (98%) of testosterone in the plasma is bound to a protein.
• 65% bound to gonadal steroid- binding globulin (GBG), 33% to albumin.
• A small amount of testosterone converts to estradiol.
• Most testosterone converts to androsterone and excreted in the urine.

Actions of Testosterone

• Testosterone regulates functions of the testes and, through the androgen receptor, exerts effects on a wide range of target cells.
• These actions include spermatogenesis, development of secondary sexual characteristics, sexual differentiation, growth of reproductive organs, and libido.
• Dihydrotestosterone (DHT) amplification occurs in some target cells.

Actions: Secondary Sex Characteristics

• Testosterone affects external genitalia (penis growth, scrotum pigmentation).
• Internal genitalia (enlargement of seminal vesicles, prostate, and bulbourethral glands).
• Voice changes (larynx enlargement, deeper voice).
• Hair growth (beard, pubic, axillary hair).
• Mental functions (increased aggression, activity, interest in opposite sex).
• Body conformation (shoulders broaden, muscles enlarge).
• Skin (sebaceous gland secretion increases, predisposing to acne).

Effects on Hairline

• Testosterone affects hair growth and loss patterns.

Actions: Anabolic Effects

• Testosterone increases protein synthesis and decreases breakdown. Increases rate of growth.
• Moderate Na+, K+, H2O, Ca2+, SO4²⁻, and PO₄³⁻ retention.
• Kidney size may be increased.
• Exogenous testosterone can increase libido but may present masculinizing, and limits usefulness in wasting diseases.
• Most estrogens in adult men are produced by extragonadal tissue or adrenal glands, not directly from the testes.

Spermatogenesis

• Sufficient testosterone concentration is needed to maintain spermatogenesis in seminiferous tubules.
• Sertoli cells produce androgen-binding protein (ABP) to maintain a high local concentration of testosterone.
• Testosterone readily diffuses through Leydig, Sertoli cells and blood testes barrier.

Regulation

• Systemically administered testosterone does not increase androgen levels.
• Inhibition of LH secretion leads to decreased testosterone synthesis and decreased sperm count.

Mechanism

• Testosterone binds to an intracellular androgen receptor (NR3C4).
• Receptor complex binds to DNA, facilitates transcription of genes.
• Testosterone can be converted to DHT 5α-reductase, in some target cells.
• DHT binds to the same intracellular receptor.
• DHT-receptor complexes are more stable than testosterone-receptor complexes.

Abnormalities of Testicular Function

• Cryptorchidism: Undescended testes.
• Male Hypogonadism classifications are:
  • Hypergonadotropic (High LH, low testosterone: testicular failure).
  • Hypogonadotropic (Low testosterone, normal or low LH).
• Long Term Effects: Loss of libido with related symptoms.
• Adolescent effects are usually permanent, tall, narrow shoulders, small muscles, a body configuration resembling the female.
  • High-pitched voice, sparse hair.

Congenital 5α-Reductase Deficiency

• Genetic mutation of 5α-reductase 2 gene.
• Male internal genitalia (testes) but female external genitalia.
• At puberty, LH secretion and circulating testosterone increase.
• Develop male body contours, libido increases.
• Clitoris enlargement ("penis-at-12 syndrome") enough testosterone may overcome need for DHT.
• Prostatic hyperplasia treatment includes 5α-Reductase inhibiting drugs.

Other Hormones

• Relaxin is a polypeptide hormone.
• Present in the corpus luteum, uterus, placenta, mammary glands (in women), and prostate (in men).
• It facilitates delivery during pregnancy by relaxing pubic symphysis and other pelvic joints.
• It also inhibits uterine contractions, and plays a role in mammary gland development.
• Found in non-pregnant women in corpus Luteum and endometrium during secretory phase; and in semen, aiding motility/penetration of ovum.
• Inhibins are produced by Sertoli cells (males) and granulosa cells (females).
• Inhibits FSH secretion.
• Activins stimulate FSH secretion, but their role is unclear.