Physiology_Levy

Physiology_Levy. Most symptoms associated with menopause result from estrogen deficiency. The vaginal epithelium atrophies and becomes dry, and bone loss is accelerated and may lead to osteoporosis. The incidence of coronary artery disease increases markedly after menopause. Hot flashes result from periodic increases in core temperature, which produces peripheral vasodilation and sweating. Hot flashes are thought to be linked to increases in LH release and are probably associated not with the pulsatile rise in LH secretion but rather with central mechanisms controlling GnRH release. Hot flashes typically subside within 1 to 5 years of the onset of menopausal symptoms. 1. The reproductive systems are composed of gonads, an internal reproductive tract with associated glands, and external genitalia. Mammary glands are accessory reproductive glands in women. 2.


Physiology_Levy

Physiology_Levy. 1. The reproductive systems are composed of gonads, an internal reproductive tract with associated glands, and external genitalia. Mammary glands are accessory reproductive glands in women. 2. Gonads have two main functions: production of gametes and production of hormones. Hormones (primarily sex steroids) are absolutely necessary for normal function of the reproductive system, and their production is regulated by a hypothalamic-pituitarygonadal axis. 3. Seminiferous tubules in the testis contain Sertoli cells and developing sperm cells. 4. Spermatogenesis refers to the progression of sperm cells from spermatogonia through the processes of meiosis and spermiogenesis to form mature spermatozoa. 5.


Physiology_Levy

Physiology_Levy. 4. Spermatogenesis refers to the progression of sperm cells from spermatogonia through the processes of meiosis and spermiogenesis to form mature spermatozoa. 5. Testosterone and pituitary FSH are required for normal sperm production. Only Sertoli cells express the androgen receptor and the FSH receptor, so these hormones regulate spermatogenesis indirectly through their actions on Sertoli cells. Sertoli cells produce the hormone inhibin, which negatively feeds back on pituitary FSH production. 6. Sertoli cells have many functions, including production of androgen-binding protein (ABP) and fluid and creation of the blood-testis barrier. 7. Leydig cells are stromal cells that reside outside the seminiferous tubules. They respond to LH by producing testosterone. 8. Testosterone is an active androgen. It can be converted peripherally to DHT, which is more active in certain tissues (e.g., prostate), or to estradiol. 9.


Physiology_Levy

Physiology_Levy. 8. Testosterone is an active androgen. It can be converted peripherally to DHT, which is more active in certain tissues (e.g., prostate), or to estradiol. 9. Leydig cells are regulated within a hypothalamicpituitary-testicular axis. The hypothalamus produces GnRH, which stimulates pituitary gonadotropes to secrete LH and FSH. Testosterone, DHT, and estradiol negatively feed back at the pituitary and hypothalamus and inhibit LH more than FSH secretion. Inhibin from the Sertoli cells selectively inhibits FSH. 10. Testosterone, DHT, and estradiol have numerous actions on the male reproductive tract, external genitalia, and male secondary sex characteristics, as well as on other organ systems (e.g., blood cell production, lipoprotein production, bone maturation). 11.


Physiology_Levy

Physiology_Levy. 11. The male tract includes tubal structures (epididymis, ductus deferens, and male urethra), accessory sex glands (seminal vesicles, prostate), and the penis. The seminal vesicles and the prostate produce most of the ejaculate, which nourishes, buffers, and protects sperm. 12. Penile erection involves a complex neurovascular response leading to engorgement of the erectile tissue within the penis base and shaft with blood. 13. The follicle is the functional unit of the ovary. Follicles contain epithelial cells (granulosa and cumulus) and outer stromal cells (thecal). All these cells surround a primary oocyte that remains arrested in the first meiotic prophase until just before ovulation. 14. Follicles develop from the smallest (primordial) to a large antral follicle over a period of months. The latter part of follicular development requires gonadotropins. 15.


Physiology_Levy

Physiology_Levy. 14. Follicles develop from the smallest (primordial) to a large antral follicle over a period of months. The latter part of follicular development requires gonadotropins. 15. The menstrual cycle refers to an approximately 28-day cycle that is driven by the following ovarian events: development of one large antral follicle to a preovulatory follicle (follicular phase), ovulation, and formation and death of a corpus luteum of menstruation (luteal phase). 16. The follicular phase of the ovary corresponds to the menstrual and proliferative phases of the uterine endometrium. The luteal phase of the ovary corresponds to the secretory phase of the uterine endometrium. 17. One dominant follicle is selected per menstrual cycle—usually the largest follicle with the most FSH receptors. 18.


Physiology_Levy

Physiology_Levy. 17. One dominant follicle is selected per menstrual cycle—usually the largest follicle with the most FSH receptors. 18. High levels of estradiol occur around midcycle and exert positive feedback on gonadotropin secretion. This induces the LH (and a smaller FSH) surge. The midcycle gonadotropin surge induces (a) meiotic maturation of the primary oocyte so that it progresses to a secondary oocyte (with one polar body) arrested at metaphase of the second meiotic division, (b) breakdown of the ovarian and follicular wall so that the oocyte-cumulus complex is extruded (called ovulation), and (c) differentiation of the remaining follicular cells into a corpus luteum. The corpus luteum produces high levels of progesterone, estradiol, and inhibin. 19. If pregnancy does not occur, the corpus luteum will die in 14 days. This constitutes the luteal phase of the menstrual cycle. 20.


Physiology_Levy

Physiology_Levy. 19. If pregnancy does not occur, the corpus luteum will die in 14 days. This constitutes the luteal phase of the menstrual cycle. 20. The oviducts capture the ovulated cumulus-oocyte complex and transport it medially into the oviduct and toward the uterus. Estrogen promotes ciliation and transport; progesterone inhibits transport. 21. The uterine mucosa, called the endometrium, is the normal site of embryonic implantation. The mucosa is increased in thickness in preparation for implantation and is sloughed away if no pregnancy occurs. 22. During the mid to late follicular phase (days 6–14 of the menstrual cycle), the ovary produces estradiol, which induces all cells of the endometrium to proliferate (called the proliferative phase of the uterus). 23. After ovulation the ovary enters the luteal phase (days 16–28) and produces progesterone. Progesterone stimulates secretion from the uterine glands (called the secretory phase of the uterus). 24.


Physiology_Levy

Physiology_Levy. After ovulation the ovary enters the luteal phase (days 16–28) and produces progesterone. Progesterone stimulates secretion from the uterine glands (called the secretory phase of the uterus). 24. In the absence of an implanting embryo the corpus luteum dies, progesterone production ceases, and the uterine endometrium is sloughed (called the menstrual phase, or period, of the uterus—this corresponds to days 1 to 5 of the follicular phase of the ovary). 25. The cervix is the lower portion of the uterus. Cervical mucus is hormonally regulated so that at midcycle in response to estrogen, cervical mucus promotes entry of sperm into the uterus from the vagina. During the luteal phase in response to progesterone, cervical mucus becomes thick and poses a barrier to entry of sperm and microbes into the uterus. We wish to thank Dr. Lisa Mehlmann for her advice on this chapter, and especially for help in drawing Figures 44.31 44.32


Physiology_Levy

Physiology_Levy. We wish to thank Dr. Lisa Mehlmann for her advice on this chapter, and especially for help in drawing Figures 44.31 44.32 Achar S, et al. Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids, blood pressure, left ventricular dimensions, and rhythm. Am J Cardiol. 2010;106:893-901. Coticchio G, et al. Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization. Hum Reprod Update. 2015;21:427-454. Defeudis G, et al. Erectile dysfunction and its management in patients with diabetes mellitus. Rev Endocr Metab Disord. 2015; 16:213-231. Franca LR, et al. The Sertoli cell: one hundred fifty years of beauty and plasticity. Andrology. 2016;4:189-212. Kosaka T, et al. Is DHT production by 5alpha-reductase friend or foe in prostate cancer? Front Oncol. 2014;4:article 247. 26. Fertilization is a complex series of events that occur in the oviduct and lead to penetration of the oocyte by sperm. 27.


Physiology_Levy

Physiology_Levy. 26. Fertilization is a complex series of events that occur in the oviduct and lead to penetration of the oocyte by sperm. 27. Early embryogenesis (up to day 6 after fertilization) occurs in the oviduct and gives rise to a blastocyst that hatches from the zona pellucida. 28. The placenta develops from the outer extraembryonic trophoblast. The endocrine function of the placenta includes production of hCG, progesterone, estrogens, and placental lactogen. Estrogen production requires placental cells (syncytiotrophoblasts) as well as the fetal adrenal and liver—collectively called the fetoplacental unit. 29.


Physiology_Levy

Physiology_Levy. 29. Pregnancy and the hormones of pregnancy induce major changes in maternal physiology, including an increase in insulin resistance, an increase in the use of free fatty acids by the mother, and development of the mammary glands. Mammary gland development (but not lactation) is promoted by estrogen, progesterone, and placental lactogen but also by maternal pituitary prolactin, whose secretion is stimulated by placental estrogens. 30. Oxytocin is a pituitary hormone that promotes contraction of certain smooth muscles, including myometrial contractions during labor and myoepithelial contractions in the breasts that lead to let-down of milk in response to suckling. 31. Menopause results from exhaustion of the ovarian reserve and is characterized by low ovarian hormone and elevated gonadotropin levels. Larney C, et al. Switching on sex: transcriptional regulation of the testis-determining gene Sry. Development. 2014;141:21952205.


Physiology_Levy

Physiology_Levy. Larney C, et al. Switching on sex: transcriptional regulation of the testis-determining gene Sry. Development. 2014;141:21952205. Mehlmann LM. Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation. Reproduction. 2005;130:791-799. Pasqualini JR. Enzymes involved in the formation and transformation of steroid hormones in the fetal and placental compartments. J Steroid Biochem Mol Biol. 2005;97:401-415. Sreekumar A, et al. The mammary stem cell hierarchy: a looking glass into heterogeneous breast cancer landscapes. Endocr Relat Cancer. 2015;22:T161-T176. Umetani M, Shaul PW. 27-Hydroxycholesterol: the first identified endogenous SERM. Trends Endocrinol Metab. 2011;22: 130-135.