Physiology Male Reproductive Lecture Notes 2024-25 PDF

Physiology: Male Reproductive System Page 1 of 13 Dr. Jeyasuria Pancharatnam Session Learning Objectives: 1. Summarize male reproductive functions in terms of gamete production and sperm/fluid transport. 2. Describe the physiolo...

Physiology: Male Reproductive System Page 1 of 13 Dr. Jeyasuria Pancharatnam Session Learning Objectives: 1. Summarize male reproductive functions in terms of gamete production and sperm/fluid transport. 2. Describe the physiology of the testes including functions of Sertoli & Leydig cells, endocrine role of testes, testosterone synthesis, actions of androgens, and regulation by the brain. 3. Describe the functions of the ducts and accessory glands including contributions to the components of semen. 4. Discuss some clinical problems associated with the male reproductive system. Session Outline: I. Overview of Male Reproductive System II. Physiology of the Testes A. Functions of Sertoli Cells B. Functions of Leydig Cells C. Endocrine Role of the Testes D. Biosynthesis of Testosterone E. Actions of Androgens in Male F. Hypothalamic-Pituitary-Gonadal Axis III. Functions of the Ducts & Accessory Glands IV. Male Reproductive Pathophysiology Supplemental Reading Costanzo, L.S. Physiology, 6th ed., Elsevier: Philadelphia 2018 https://www.clinicalkey.com/#!/content/book/3-s2.0-B9780323478816000107?scrollTo=%23hl0000412 Physiology: Male Reproductive System Page 2 of 13 Dr. Jeyasuria Pancharatnam I. OVERVIEW OF MALE REPRODUCTIVE SYSTEM Reproduction and thus reproductive function are part of our evolutionary need to sexually reproduce. Male reproductive function and physiology is focused on the production of the male gametes and the introduction of this gamete, the sperm, into the female reproductive tract (Figure 1). This involves spermatogenesis- the production of sperm with a haploid number (23) of chromosomes from diploid germ cells with 46 chromosomes. Figure 1 The male reproductive system (see Figure 2) consists of the: Testes, which produce gametes (sperm) and hormones Epididymis, which is involved in sperm transport and is a major site of sperm maturation Ductus deferens, also involved in sperm transport and storage Accessory glands: seminal vesicles, prostate, bulbourethral (Cowper's) glands, which produce nutrients and buffers Ejaculatory duct & urethra, which are involved in transport of sperm and fluids Figure 2. Anatomy of the male internal genitalia and accessory sex organs Physiology: Male Reproductive System Page 3 of 13 Dr. Jeyasuria Pancharatnam II. PHYSIOLOGY OF THE TESTES The testes are located in the scrotal sac outside the body cavity. The bulk of the testes consist of the seminiferous tubules, which are lined by the Sertoli cells that nurture the developing sperm (Figure 3). The Sertoli cells lining the seminiferous tubules are connected by tight junctions, forming a blood/testis barrier. This barrier keeps noxious substances from reaching the developing gametes. In between the seminiferous tubules are the Leydig, or interstitial, cells, which produce the steroid hormone testosterone (T). The Figure 3. Cross section of the seminiferous testes are maintained at a temperature 2°C tubule below basal body temperature in order to ensure proper spermatogenesis. A. Functions of the Sertoli cells The Sertoli cells surround and nurture the developing sperm (Figures 3 & 4). They have multiple functions in male reproductive physiology. They appear to secrete growth factors that regulate mitosis, meiosis and development of the spermatozoa. Figure 4: Cross section of semiferous tubule including interstitial space The Sertoli cells form a blood-testis barrier that is selectively permeable; they secrete the fluid within the lumen of the seminiferous tubules, and they secrete androgen-binding protein (ABP), which keeps concentrations of androgens very high in the tubules and ducts. Physiology: Male Reproductive System Page 4 of 13 Dr. Jeyasuria Pancharatnam Sertoli cells require: 1) Follicle stimulating hormone (FSH) 2) Testosterone to initiate spermatogenesis, and certainly testosterone, and probably FSH for maintenance of spermatogenesis. Figure 5: Leydig cell/Sertoli cell endocrine function Note that fluid pressure resulting from the continuous secretion of fluid into the lumen of the seminiferous tubules by the Sertoli cells and peristaltic contractions transport the spermatozoa through the tubules and the epididymis. B. Function of the Leydig cells The major function of the Leydig cells is to synthesize and secrete testosterone; they produce >95% of the testosterone in the male. Luteinizing hormone (LH) is necessary for this process. The two crucial steps in testosterone synthesis (Figure 5) are (1) the conversion of cholesterol to pregnenolone, and (2) cleavage of the side chain at C-17. In addition to testosterone secretion, LH is also required for maintenance of the Leydig cells themselves. The testes have two primary functions – gametogenic and endocrine. The gametogenic function of the testes has been adequately described in the Histology lecture of the Male Reproductive System and will not be repeated here. Physiology: Male Reproductive System Page 5 of 13 Dr. Jeyasuria Pancharatnam C. Endocrine Role of the Testes The major androgen produced by the testes is testosterone (T). In a young adult male, about 7 mg of testosterone are secreted daily; most of the circulating hormone is bound to albumin and sex hormone binding globulin (SHBG). Table 1: Hormone concentrations Testosterone is metabolized peripherally to a more potent androgen, dihydrotestosterone (DHT) (Table 1) through the action of 5-alpha reductase enzyme. This enzyme is found in skin, prostate, and other genital tissues. Testosterone can also be metabolized peripherally to 17-beta estradiol (E2) through the action of the enzyme aromatase. The aromatase is found primarily in brain, adipose tissue, and breast. Any remaining peripheral testosterone is metabolized in the liver. Physiology: Male Reproductive System Page 6 of 13 Dr. Jeyasuria Pancharatnam D. Biosynthesis of Testosterone Testosterone is synthesized primarily in Leydig cells of the testes. The key step is the conversion of cholesterol to pregnenolone via a side chain cleavage enzyme. Pregnenolone, after two steps, is converted to dehydroepiandrosterone (DHEA) and then to testosterone (Figure 6). Figure 6: Steroid biosynthesis Physiology: Male Reproductive System Page 7 of 13 Dr. Jeyasuria Pancharatnam E. Actions of Androgens in the Male Like the other steroid hormones, testosterone and dihydrotestosterone, act by binding to a specific intracellular receptor, the androgen receptor, which leads to alterations in transcription and ultimately to changes in the levels and species of proteins produced (see Figure 7). Testosterone and dihydrotestosterone bind to the same receptor; DHT binds more tightly, which explains its greater potency. Figure 7: Androgen action and outcomes Androgens promote the growth, differentiation and function of the accessory organs of reproduction. They are also essential in the maintenance of normal function in the adult. Androgens are necessary for spermatogenesis - they are specifically required for the differentiation of spermatids into spermatozoa. Without androgens, the secretory epithelia of the seminal vesicles and prostate atrophy. Androgens stimulate growth of chest, axillary and facial hair, as well as recession of hair at the temples and the development of male pattern baldness. At puberty, androgens stimulate the growth and secretions of the sebaceous glands of the skin, the growth of the larynx and thickening of the vocal cords, and the growth of bone and increased muscle mass. Appetite and food intake are also increased. Androgens also increase the libido. Testosterone is responsible for the maturation of the Wolffian duct structures and formation of the male internal genitalia during development, for spermatogenesis, for the increased muscle mass and libido. DHT is needed for the development of the male external genitalia, enlargement of the prostate and probably of the penis during puberty, for facial hair, increased tendency to acne, and recession of the hairline at the temples. Athletes using androgens, to improve performance, cause a hypothalamic feedback that reduces testicular size and spermatogenic loss. Physiology: Male Reproductive System Page 8 of 13 Dr. Jeyasuria Pancharatnam F. Hypothalamic-Pituitary-Gonadal Axis Regulation of Testicular Function LH, FSH and testosterone are required for testicular function. LH acts on the Leydig cells to stimulate testosterone production and secretion. Testosterone, in concert with FSH, stimulates the Sertoli cells. Figure 8: Pulsatile LH LH and FSH are released from the pituitary in response to Gonadotropin Releasing Hormone (GnRH). GnRH is a decapeptide hormone produced by neurons in the hypothalamus and is released into the portal circulation in pulses with a frequency of once an hour to once every 3 h. This causes release of LH and of FSH, also in a pulsatile manner (Figure 8). LH and FSH are glycoproteins consisting of an alpha and β sub units. The alpha subunits are similar while the β subunits determine receptor-binding specificity. LH is similar to hCG (human chorionic gonadotropin) and differs in the first 23 amino acids of amino terminal. hCG is used to treat men with hypogonadotropic hypogonadism because it works like LH to upregulate testosterone production but also has a longer pharmaceutical half life. The Hypothalamic-Pituitary-Gonadal Axis (HPG) works through a classical endocrine feedback loop. Testosterone inhibits GnRH secretion by decreasing the frequency of pulses and also reduces LH secretion by the pituitary. The Sertoli cells produce a hormone called inhibin, which directly inhibits FSH secretion by the pituitary (Figure 9). FSH also causes the Sertoli cells to produce inhibin that in turn feeds back to block FSH Figure 9: Hypothalamic pituitary gonadal axis production in the pituitary. Physiology: Male Reproductive System Page 9 of 13 Dr. Jeyasuria Pancharatnam III. FUNCTIONS OF THE DUCTS AND ACCESSORY GLANDS The main function of the ducts is sperm transport. The epididymis also functions in sperm maturation and the ductus deferens also functions in sperm storage. The seminal vesicles, bulbourethral glands, and prostate gland secrete components of the semen. The seminal vesicles secrete slightly over half the total volume; the prostate secretes approximately 20% of the total volume. Among the components are fructose, ascorbic acid, prostaglandins, citric acid, phosphate and bicarbonate. The below Table 2 summarizes the composition of semen as related to contributions from accessory glands. Table 2: Semen Composition Concentration of sperm 100 million/ml semen average 20 – 50 million/ml, fertility is impaired