Male Reproductive Physiology PDF Fall 2023

Male Reproductive Physiology Maureen Basha PhD [email protected] Nursing Physiology, Fall 2023 11/17/2023; 9:00-10:00 AM Male gonadal structure and function Sex steroid biosynthesis HPG axis in biological males Spermatogenesis Mechanism of Erection Male Reproductive Physiology: Big picture ➢ Two k...

Male Reproductive Physiology Maureen Basha PhD [email protected] Nursing Physiology, Fall 2023 11/17/2023; 9:00-10:00 AM Male gonadal structure and function Sex steroid biosynthesis HPG axis in biological males Spermatogenesis Mechanism of Erection Male Reproductive Physiology: Big picture ➢ Two key functions of the male gonad: • Produce gametes by process of spermatogenesis • Produce sex steroid hormones (androgens ) ➢ Key function of the penis is sexual stimulation and delivery of gametes: • The process of erection is regulated by the Parasympathetic nervous system (Point) • The process of emission is regulated by the Sympathetic Nervous System (Shoot) “POINT AND SHOOT” Learning Objective 1 Describe the 3 types of sex steroids , the process of sex steroid biosynthesis in males and the pathways of testosterone action. List the effects of testosterone in the male. SEX STEROIDS ➢ Androgens: • Biologically active: Testosterone, Dihydrotestosterone (DHT) • Weak androgens : androstenedione, DHEA ➢ Estrogens: • Biologically active: 17-β estradiol • Weak estrogens: estrone, estriol ➢ Progestens: • Biologically active: progesterone Biologically active hormones bind tightly to steroid receptors within cells to alter gene transcription and protein synthesis. Pathway for Sex Steroid Biosynthesis: Males Fig 17.6 ➢all synthesized from cholesterol ➢Adrenal gland secretes “ weak” androgen: low binding affinity for receptor ➢Males: • Predominant sex steroid produced by gonad (testes): testosterone. • Testosterone released from testes travels in blood stream and converted to DHT in cells that have the enzyme 5 alpha reductase • Carrier proteins for testosterone: sex hormone binding globulin (SHBG) and albumin Testosterone Effects in Males Negative Feedback (INTERNAL GENTILIA) Note External genitalia and prostate: Testosterone needs to be converted to DHT ( bone: via conversion to estrogen) Spermatogenesis requires HIGH TESTOSTERONE LEVELS WITHIN THE TESTES Two important enzymes involved in sex steroid biosynthesis 1. Aromatase: converts androgens to estrogens 2. 5 alpha reductase (5 α reductase) : converts testosterone to dihydrotestosterone Testosterone is both a hormone that stimulate androgen receptors and a precursor for synthesis of other hormones Testosterone may be converted to : • Dihydrotestosterone (DHT): SOME tissues have the enzyme 5 alpha reductase within cells and convert testosterone to DHT. prostate gland and hair follicles • Estrogen: SOME tissues have the enzyme aromatase within cells and convert testosterone to estrogens (E) bone 5 α reductase Testosterone testosterone Testosterone aromatase Testosterone TESTE DHT Target cell Estrogen Learning Objective 2 Testicular changes across the male lifespan In utero development birth puberty ➢ fetal testes ➢ transient surge of ➢ Awakening of the HPG produce testosterone in first axis: pulsatile testosterone: three months “mini secretion of GnRH differentiation of puberty” male genitalia • further genital ➢ ↑ Testosterone: • Internal: growth • initiation of testosterone • ↑ growth spermatogenesis • External: velocity converted to • later • Spermarche: first DHT reproductive release of semen function? • secondary sexual characteristics aging male ➢ Fertility persists but sperm # and quality decreased ➢ Slow decline in testosterone (T) ➢ andropause: ↓ T with symptoms of deficiency • not universal • Tx androgen replacement Leydig, Sertoli Cells and germ cells of the Testes Cross section of seminiferous tubules • Leydig cells: outer cells that produce testosterone • Sertoli cells: cells of seminiferous tubule wall “ nurse cells” for gamete production (spermatogenesis) and form the “BLOOD-TESTES barrier • Germ cells (spermatogonia): cells that develop into gametes (spermatozoa) Spermatogenesis takes place between adjacent Sertoli cells in walls of seminiferous tubules Control of the Testes By the HPG Axis FSH : stimulate Sertoli cell secretions • growth factors to support spermatogenesis • inhibin: peptide hormone negative feedback on FSH from anterior pituitary Pulsatile secretion of GnRH from hypothalamus Pulsatile secretion of LH and FSH from anterior pituitary Figure 17.14 LH : stimulate Leydig cell testosterone (T) production Effects of Testosterone: • negative feedback on hypothalamus and anterior pituitary • Supports spermatogenesis (local effect on Sertoli Cells) • effects on peripheral targets Learning Objective 3 Explain the process of spermatogenesis and the conditions required for this process. Spermatogenesis: Male Gamete Production Diploid germ cell (spermatogonia)- haploid gamete (spermatozoa) ~ 70 days Once males reach puberty the germ cells within the gonad (spermatogonia) are constantly undergoing mitosis to produce new spermatozoa! Stages of Spermatogenesis: 1. mitosis: spermatogonial proliferation (diploid germ cells divide to produce new diploid cells) 2n 2n 2n 2. meiosis: production of 4 haploid cells (spermatids) from a diploid cell n 2n n n n 3. spermiogenesis: transformation from round spermatids into spermatozoa n n n n Requirements for spermatogenesis in the testes ➢Follicle Stimulating Hormone (anterior pituitary) • receptors on Sertoli cells • Sertoli cells provide support of developing spermatozoa ➢Luteinizing Hormone Stimulation (anterior pituitary) of Testosterone production (testes) FSH Sertoli Cells • Receptors on Leydig cells • Stimulates Testosterone production • Testosterone also acts WITHIN the testes ( paracrine effect) to support spermatogenesis LH ➢Temperature 2-4 °C BELOW core body temperature: Leydig Cells • Testes housed in scrotum outside of pelvic cavity • Cremaster muscles→ alter scrotal position with temperature changes • Pampiniform plexus→ heat exchange between veins and arteries in spermatic cord TESTOSTERONE Learning Objective 4 Explain the mechanism of penile erection. Describe the relationship between NOS , NO, cGMP and smooth muscle relaxation and the central role of PNS in the process of erection. Penile Erection: INCREASED activity of parasympathetic nerves to the penis arteries nerves veins ➢ Erection: triggered by signals from brain and/or by mechanoreceptors within the penis ➢ Activation of Parasympathetic Nerves to the penis stimulates erection • Key signaling molecule released from parasympathetic nerves is NITRIC OXIDE (NO) ! Corpus cavernosum From: Nature Urology, 2019, Vol 16 Effects of Nitric Oxide: • RELAX vascular smooth muscle (dilate blood vessels): increase blood flow into penis • RELAX smooth muscle of erectile tissue (corpus cavernosum): engorge sinuses with blood Erection: Putting it all together ↑ PNS activity arteries nerves veins ↑ NO release Arteries dilate Corpus cavernosa relax Corpus cavernosum ( sinusoids) Increased blood flow Sinusoids can more easily fill Expansion of sinusoids with blood ( this also compresses the veins): erection! MORE BLOOD IN AND LESS BLOOD OUT ! Engorgement of blood and Erection How do PDE-5 inhibitors work? (i.e. Viagra) • Nitric oxide activates an enzyme (guanylyl cyclase) that converts GTP to cGMP (cyclic GMP) • Increased cGMP triggers changes that results in smooth muscle relaxation • cGMP is broken down into inactive form by a phosphodiesterase (PDE5) Parasympathetic Neuron or endothelial cell PDE-5 inhibitors Phosphodiesterase type 5 inhibitors (i.e. Viagra) • PDE 5 inhibitors: Inhibits the action of the enzyme phosphodiesterase • PDE-5 inhibitors increase amounts of cGMP available for promoting vascular and erectile tissue relaxation Summary • Testosterone is the main hormone produced by the testes and acts directly on target tissue via binding to androgen receptors. Some testosterone released into the blood is also converted to DHT and estradiol in peripheral tissues. • Testicular hormone production begins during fetal development and is critical for development of genitalia. Testosterone increases at puberty and gives rise to secondary sexual characteristics and initiation of puber • The testes are under negative feedback control by the hypothalamus (GnRH) and anterior pituitary (LH, FSH). There is a division of labor of cell types of the testes with Leydig cells producing testosterone and Sertoli cells playing a key role in the process of spermatogenesis. • Spermatogenesis is a process that involves mitosis, meiosis and spermiogenesis and takes place over a period of just over 2 months to complete. LH stimulation/High intratesticular testosterone production, FSH stimulation and slightly lower temperatures are required for the process. • Erection involves smooth muscle RELAXATION and occurs in response to PNS stimulation. Nitric oxide is a key signaling molecule involved with the process of erection and leads to production of cGMP which mediates smooth muscle relaxation. Viagra works by preventing the breakdown of cCMP by inhibiting the action of phosphodiesterase-5.