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Chapter 20. Endocrine Regulation of Reproduction . 20-19. Interactions Between the Hypothalamus, Anterior Pituitary, and Gonads. Hypothalamus controls release of LH and FSH from anterior pituitary (Ant Pit) with GnRH
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Interactions Between the Hypothalamus, Anterior Pituitary, and Gonads • Hypothalamus controls release of LH and FSH from anterior pituitary (Ant Pit) with GnRH • LH and FSH stimulate production of sperm and eggs, and gonadal sex steroids; and maintain size of gonads • Sex steroids provide negative feedback on hypothalamus and Ant Pit • Gonads also secrete hormone inhibin which negatively feeds back on FSH secretion 20-20
Onset of Puberty • FSH and LH secretion is high for 1st 6 months of life, but falls to very low levels until puberty • At puberty hypothalamus increases GnRH secretion • This stimulates increased LH and FSH • Which stimulates sex steroid secretion • Which drives changes in secondary sex characteristics and menarche (1st menstrual flow) • Growth of pubic and axiliary hair is due to androgen secretion from adrenal cortex 20-21
Growth as a Function of Sex and Age • At beginning of female puberty, high E stimulates growth • High pubertal Testost. in boys causes growth spurt that lags that of girls • Age of puberty in girls depends on % body fat and physical activity • Girls with low body fat and high activity levels enter puberty at older age 20-22
4 Phases of Human Sexual Response • Excitation phase (arousal) is characterized by increased muscle tone and engorgement of sexual organs with blood • Includes nipples, clitoris, penis, and labia minor • Vagina lubricates • During plateau phase clitoris is partially hidden by swelling labia • Areolae continue swelling • Outer third of vagina engorges 20-24
4 Phases of Human Sexual Response continued • During orgasm, men ejaculate and women have analogous contractions of uterus and vagina • In theresolution phase, body returns to preexcitation conditions • Men enter refractory period 20-25
Male Reproductive System 20-26
Male Reproductive System • Testes contain seminiferous tubules (STs) where spermatogenesis occurs; and interstitial tissue housing Testost.-secreting Leydig cells • Sertoli cells of STs contain receptors for FSH • FSH stimulates spermatogenesis • Leydig cells contain LH receptors • LH stimulates secretion of Testost. 20-27
Control of LH and FSH Secretion • Is by negative feedback • Testost. inhibits LH and GnRH secretion but not FSH • Inhibin from Sertoli cells provides negative feedback on FSH 20-28
Testosterone Derivatives • Effects of Testost. in brain are mediated by its derivatives • Testost. can be converted to DHT and others • Or can be converted to estradiol by aromatase • Estradiol mediates negative feedback effects of Testost. 20-29
Testosterone and Age • Secretion of Testost. declines gradually and varyingly in men> 50 • Causes are unknown • Not due to low GnRH, LH, or FSH because their levels are elevated 20-30
Interactions Between the 2 Comparments of the Testes • Testost. Secreted by Leydig cells stim. spermatogenesis in tubules • Leydig cells may also secrete ACTH, MSH, and -endorphin • Secretion of inhibin by tubules may affect sensitivity of Leydig cells to LH stim. 20-31
Spermatogenesis • Germ cells that migrate from yolk sac during development become spermatogonia(stem cells) • Spermatogonia replicate selves throughout life by mitosis • Give rise to haploid sperm by meiosis 20-32
Spermatogenesis continued • Occurs in wall of Seminiferous Tubules • Spermatogonia and primary spermatocytes are located in outer part of ST • Spermatids and mature spermatozoa are located toward lumen • Tails of spermatozoa are in lumen 20-33
Spermiogenesis • = maturation spermatids into spermatozoa • Requires participation of Sertoli cells • Most of their cytoplasm is pinched off and ingested by surrounding cytoplasm of Sertoli cells 20-34
Spermiogenesis continued • During spermiogenesis, proteins called protamines replace the DNA-associated histones • Cause extreme compaction of chromatin, changing nuclear shape • Sertoli cells phagocytize cytoplasm of developing sperm • A flagellum and acrosome (cap of digestive enzymes) develop • At end of spermiogenesis, spermatozoa are released into the lumen 20-35
Sertoli Cell Function • Autoimmune destruction of developing sperm is prevented by blood-testes barrier created by Sertoli cells • and by Sertoli-secreted FAS ligand that triggers apoptosis of T lymphocytes • Spermatogonia and developing spermatozoa are embedded in, and nurtured by, adjacent Sertolis 20-36
Sertoli Cell Function continued • Sertolis secrete androgen-binding protein (ABP) into lumen of Seminiferous Tubules • ABP binds testosterone, concentrating it in tubules • FSH stimulates spermiogenesis through its receptors on Sertolis • Sertolis provide negative feedback on FSH via production of inhibin 20-37
Spermatozoa • Have oval-shaped head that contains DNA and the acrosome (a cap of digestive enzymes) • Have a midpiece and flagellar tail • Tail will become motile in epididymus 20-38
Hormonal Control of Spermatogenesis • Formation of primary spermatocytes and entry into early prophase I, begin during embryonic development • Spermatogenesis is then arrested until puberty • Testosterone and its metabolites are required for completion of meiosis and spermatid maturation • A number of paracrines may also be involved • FSH is not essential for spermatogenesis • It enhances Testost.-stimulated spermatogenesis • And at puberty acts with Testost. to stimulate proliferation of Sertolis 20-39
Male Accessory Sex Organs • Spermatozoa and fluids exit Seminiferous Ttubules via rete testis • Pass through efferent ductules to epididymis and leave through vas deferens 20-40
Male Accessory Sex Organs continued • Spermatozoa entering epididymis are non-motile and cannot fertilize • In part because pH is low • Spermatozoa mature and become motile in epididymis • Prostatic fluid neutralizes pH during ejaculation 20-41
Male Accessory Sex Organs continued • Vas deferens carries sperm into pelvic cavity • Seminal vesicles add fluid (constituting 60% of ejaculate) to that coming from epididymis • Contains fructose for energy for sperm • Vas deferens becomes ejaculatory duct which merges with urethra in prostate 20-42
Male Accessory Sex Organs continued • Fluid becomes semen when prostate adds secretions containing citric acid, Ca2+ and coagulation proteins • Which coagulate semen during ejaculation 20-43
Erection • Is controlled by hypothalamus and sacral cord • Occurs as result of Parasymp-induced blood flow into erectile tissues of penis • NO is the neurotransmitter • Erectile tissues include corpuscavernosum and spongiosum • Venous outflow is partially occluded, aiding erection 20-44
Emission and Ejaculation • Emission is movement of semen into urethra • Ejaculation is forcible expulsion of semen from urethra out of penis • Both are stimulated by sympathetic activity • Which also causes peristalsis of tubular system, contractions of seminal vesicles, prostate, and muscles at base of penis 20-45
Male Fertility • Normal volume of ejaculate is 1-5 ml • With 60-150 million sperm/ml • Sperm count of < 20 million/ml constitutes oligospermia • Associated with decreased fertility • Caused by heat, lead or arsenic poisoning, and drugs • Including marijuana, cocaine, and anabolic steroids 20-46
Male Contraception • Efforts have targeted gonadotropin secretion (with limited usefulness because of side effects) • Gossypol interferes with sperm development (but also has side effects) • Vasectomy is one of most widely used methods • Each vas deferens is cut and tied • Sperm can’t enter urethra; accumulate in crypts along reproductive tract • Where sperm are phagocytosed by immune system • 70% develop anti-sperm antibodies 20-47
Female Reproductive System • Ovaries contain large number of follicles that produce female gametes (eggs or ova) in ovarian cycle • Extensions of fallopian tubes called fimbriae partially cover each ovary • The cilia of its lining draw in ovulated eggs 20-49
Female Reproductive System continued • Uterus has 3 layers: • Perimetrium is outer layer of connective tissue • Myometrium is middle layer of smooth muscle • Endometrium is hormonally-responsive inner epithelial layer that is shed during menstruation • Between uterus and vagina is cervix 20-50
Accessory Sex Organs • Consist of vagina, uterus, and fallopian tubes • Vaginal opening is just posterior to urethra • Both are covered by labia minora and majora • Erectile clitoris is at anterior margin of labia minora 20-51
Production of Oocytes • Germ cells that migrate into ovaries from yolk sac multiply so that at 5 mo. gestation, ovaries contain 6-7 million oogonia • Production of oogonia then ceases forever • Toward end of gestation, oogonia (now 1ooocytes) begin meiosis but arrest in prophase I • There is a continual loss of 1o oocytes throughout life • At birth are 2 million left • At puberty 400,000 are left • 400 oocytes are ovulated during reproductive years; rest undergo apoptosis 20-52
An Ovary Containing Follicles at Different Stages of Development • Primary oocytes are contained in primaryfollicles • Consisting of oocyte + follicle cells • In response to FSH some follicles enter ovarian cycle and grow, producing layers of granulosa cells • Some primary follicles continue, developing vesicles and becoming secondaryfollicles 20-53
Ovary continued • One follicle continues growth • Vesicles fuse, forming fluid-filled cavity called an antrum • Is now called a graafian follicle 20-54
Ovarian Cycle continued • As graafian follicle develops, primary oocyte completes meiosis I • This is an asymmetric division because 1 daughter cell (the secondaryoocyte) gets all cytoplasm • Other daughter becomes a small polar bodywhich will degenerate • secondaryoocyte arrests at metaphase II • Only fertilized eggs complete meiosis II 20-55
Ovary continued • Secondary oocyte is part of graafian follicle • Granulosa cells form layer around outside of follicle • Oocyte sits on mound in this layer called cumulus oophorus • secondary oocyte is enclosed by ring of granulosa cells called corona radiata • Between oocyte and radiata is gelatinous layer called zona pellucida • Which forms barrier to sperm penetration 20-56
Ovary continued • By 10-14 days after menstruation begins, only 1 follicle survives • Others become atretic follicles (degenerate) • Surviving graafian follicle forms bulge on surface of ovary • Secretes increasing levels of Estrogen 20-57
Ovary continued • Graafian follicle releases egg into fallopian tube at ovulation 20-58
Ovary continued • If fertilized, oocyte completes meiosis II with formation of another polar body • oocyte degenerates in 2 days if not fertilized 20-59
Ovary continued • LH causes empty follicle to become corpus luteum (CL) • Which secretes progesterone (P) and Estrogen • If no fertilization, becomes corpus albicans(non- functional remnant) 20-60
Menstrual Cycle 20-61
Menstrual Cycle • Is ~month-long cycle of ovarian activity seen in higher primates • Characterized by shedding of endometrial lining and bleeding (menstruation) • And sexual receptivity throughout cycle • Other animals have estrous cycles in which there is no shedding of endometrium and receptivity is limited • In estrous animals that bleed (dogs and cats), it is due to high Estrogen that accompanies receptive period 20-62
Menstrual Cycle continued • In humans is ~28 days • Day 1 is taken to be first day of menstruation • Days 1 thru ovulation constitute the follicular phase • Time from ovulation to menstruation is luteal phase • Endometrial changes are called: menstrual, proliferative, and secretory phases 20-63
Follicular Phase • Lasts from day 1 to about 13 • Is dominated by growth and death of a cohort of primary follicles into secondary follicles • With 1 survivor becoming a graafian follicle • Which will undergo ovulation • As follicles grow, secrete larger amounts of Estrogen • Reaching peak about day 12 20-64
Follicular Phase continued • Follicular growth and Estrogen secretion are dependent on FSH from Ant Pit • FSH and Estrogen induce formation of FSH receptors in granulosa cells • Causing follicles to become increasingly sensitive to same level of FSH • At same time, FSH and Estrogen recruit LH receptors in graafian follicle 20-65
Follicular Phase continued • Rapidly rising Estrogen secretion causes: • Hypothalamus to increase pulses of GnRH • And Ant Pit sensitivity to GnRH to increase, resulting in greater LH secretion • A positive feedback between Estrogen and Ant Pit secretion develops • Resulting in LH surge that peaks 16 hrs before ovulation • And causes ovulation 20-66
The Cycle of Ovulation and Menstruation • After ovulation, LH causes empty follicle to become the corpus luteum (CL) which secretes Estrogen and Progesterone 20-67
Luteal Phase continued • Progesterone levels rise and peak about a week after ovulation • Development of new follicles and another ovulation are inhibited by: • High Progest. and Estrogen exert strong negative feedback on LH and FSH • Inhibin from Corpus Luteum further suppresses FSH 20-68