Gonad and Hormons

Gonad and hormons 1 Sex hormons • Sex hormones are steroids • and synthesis by testes and ovaries ( main source) • and a little bit by Cortex of Adrenal ( reticular part ) and placenta 2 Females and males reproductive system  The female reproductive system is much more complicated than the male reproductive system  The male produces sperm at a constant rate  The female has a complicated cycle in which an egg (ovule) matures  The hormonal levels of the female fluctuate( changes) throughout her reproductive years until menopause. 3  In female, the reproductive system function as follows:  Hypothalamus releases gonadotropic releasing hormone (GnRH) that reaches to the anterior pituitary  Then, Pituitary releases FSH in blood, then reaches to ovary and stimulate the follicles in the ovary to be mature  The follicle releases estrogen which causes thickening endometrial lining of the uterus  The estrogen, at midcycle, also causes stimnlating the pituitary to release LH and stop the secreting FSH 4 5 • Female Sex Hormones (Estrogens and Progestins) • The ovaries of sexually-mature females secrete: 1-a mixture of estrogens of which 17β-estradiol is the most abundant and most potent. 2- progesterone.  Control the Female Sex Hormones secretion:  Follicle –Stimulating Hormone (FSH) stimulates the production of Estrogens. Luteinizing Hormone (LH) stimulates the production of Progestins. 6 The Feedback Loop and LH function  The rise in LH secretions cause ovulation to occur .  LH makes the remaining follicles turn into  ( convert to) the corpus luteum.  The corpus luteum secretes both progesterone and a small level of estrogen which promote the building up of the endometrium.  As progesterone and estrogen are built up in the female very much, they inhibit the release of FSH and LH from the pituitary.  This causes the corpus luteum to be destroyed and thus decrease the levels of estrogen and progesterone which cause menstruation . 7 Mifepristone: a synthetic steroid that inhibits the action of progesterone, given orally in early pregnancy to induce abortion. 8 Estrogens • Estrogens are synthesis by ovarian follicles and corpus lutem in non pregnant and by placenta in pregnant  17 β estradiol and estrone are the main estrogen hormones which are synthesis by ovarian • • 17 β estradiol and estrone are also synthesis by other tissues like liver, muscles and adipose tissues from dihydroepiandrostrone, androstenedione and testosterone, by aromatase Enz. 9 Secretion and Transportation of estrogens in circulation  More than 97% of estradiol in circulation are bound to carrier proteins  1-3 % of β estradiol and estrone are free ( active form)  SHBG( sex hormone binding globulin) Affinity for estradiol is 1.5 times the affinity for testosterone and DHT  SHBG levels is depend on estrogen hormones and it is higher in women rather than men  SHBG levels is increased by contraceptives uptake and hyperthyroidism 10 Estrogen mechanism and function • • It Passes from cell membrane bind to receptor in cytosole H-R complex H-R enters in nucleus and bind to DNA (Hormone Response Element (HRE) fuction • In liver estradiol and estrogen other Metabolites including : 16 α hydroxylase • Estrone under 16 α hydroxylation Estriol • Estradiol, Estrone and estriol under conjugation with glucoronic and sulfate acids soluble and excreted in urine 11 Estrogens ( Functions) • Estrogens are steroids. • Firstly responsible for the conversion of girls into sexually-mature women. – For development of breasts – For further development of the uterus and vagina – For enlarging (broadening ) of the pelvis – For growth of pubic and axillary hair – It increases in adipose (fat) tissue • It participates in the monthly preparation of the body for a possible pregnancy • It participates in pregnancy if it occurs 12 Non-reproductive effects of estrogen : • Estrogens also have non-reproductive effects. • They antagonize the effects of the parathyroid hormone, • It is Minimizing the loss of calcium from bones and thus helping to keep bones strong. • They promote the blood clotting 13 • • • • • Progesterone Progesterone is also a steroid. It has many effects in the body, It is Important for sex and reproduction. It is s important in menstrual cycle and pregnancy 14 • Progesterone is synthetized from cholesterol in corpus lutem of ovary • It is carried in circulation by Cortisol binding globulin (CBG) • 10-20% of Progesterone of circulation is free • Its synthesis and secretion are in creased in pregnancy up to 300mg / day by placenta • Its production in luteal phase is 30g/day 15 Progestrone mechanisem • Liver is the main organ for progesterone Up take from circulation • Pregnandiol ( inactive form) is the main progesterone metabolite • Pregnandiol ( inactive form) will be conjugated with glucuronic acid and excreted by urine • progesterone changes the endometrial uterine • After ovulation by corpus luteum , Progesterone induces the endometrial growth and its preparation for blastocyte cells ( cells that converted to fetus in several steps) protection and feeding • Progesterone causes increase of body temperature in luteal phase • Progesterone causes the ovulation inhibition and LH production • Progesterone plus estrogen cause the growth of milk gland 16 Progestrone synthesis and secretion period • Until 6-8 weeks of pregnancy, Progesterone is synthesized and secreted by corpus luteum • With increase of pregnancy period, progesterone secretion will be three times by placental secration also • Maternal cholesterol is needed for progesterone synthesize by Placenta, because placenta can not synthesize the cholesterol from acetyl CoA • • 17 • How estrogens and progesterone exert their effects • Steroids like estrogens and progesterone are small, hydrophobic molecules that are transported in the blood bound to a serum globulin. • 1-In "target" cells ( ovary), they bind to receptor proteins located in the cytoplasm. • 2-The hormone-receptor complex enters the nucleus (if it formed in the cytoplasm) and binds to specific sequences of DNA that is called the estrogen (or progesterone) response elements to appear function • 18 • 3-Response elements are located in the promoters of genes. • 4-The hormone-receptor complex (H-R) acts as a transcription factor (often utilizing other transcription factors to help) which turns on (or sometimes turns off) the transcription of those genes. • 5-Gene expression in the target cell produces the response 19 • Regulation of Estrogen and Progesterone: • The synthesis and secretion of estrogens is stimulated by follicle-stimulating hormone (FSH), which is, in turn, controlled by the releasing gonadotropin hypothalamic hormone (GnRH). • Hypothalamus→GnRH→Pituitary →Follicle→Estrogens FSH 20 Menstrual Cycle Ovulation: Day 14 of cycle The egg bursts from the ovary and into the oviduct. • The corpus luteum is made from the follicles around where the egg burst. • There is a slight dip ( slop) in estrogen level when the burst occurs. 21  Luteal Phase: Days 15-28:  Estrogen and progesterone are secreted by the corpus luteum.  Progesterone continues to stimulate the thickening of the uterine lining as well as preventing from further ovulation and uterine contractions.  If the egg is not fertilized, the concentrations of estrogen and progesterone drop which causes a return to the flow phase. 22 • Birth control pills contain high concentrations of progesterone which inhibits the ovulation and thereby prevents the conception( pregnancy) 23 Males • Hypothalamus→GnRH→Pituitary →LH→Testes→Testosterone • The level of testosterone is under negativefeedback control: • A rising level of testosterone suppresses the release of GnRH from the hypothalamus. • This is exactly parallel to the control of estrogen secretion in females. 24 • Testes is the gonad in male • • • • Testes and function : Testes has two functions including : 1- Spermatozoid synthesis 2-Testestron synthesis and secretion • Testes is consisted of three kinds of cells including: • 1- Spermatogonia cell which synthesize the sperm • • 2- Lydig cell which secreat the testosterone and has receptor for LH • 3- Sertoli cells which has FSH receptor and synthesize two proteins including: 25 • a- Androgen binding protein( ABP) • b- Inhibin (A FSH controlling protein) which inhibit the FSH secretion • The whole properties spermatozoid protection are necessary for 26 • Testes Mechanisms: • In lydig cells: LH + receptor Adenylate cyclese • cAMP transfer Cholesterol to mitochondria • Spermatozoid and testestrone synthesis induction • In sertoli cell : FSH+ receptor ABP synthesis induction Testosterone transfer to semen tubes (Spermatozoid cells synthesis site) testosterone concentration in semen tubes Inhibin synthesis induction • In spermatogonia : Sperm synthesis 27 Anrogens synthesis: 1 Cholesterol pregnolon 2 17 OH- pregnolon progesterone 2 1 17-OH progesterone 3 Di hydroepiandrestrone 4 DHT Andrestondeion ( Dihydrotestosterone) 3 1 Andrestondeion 4 reductase testostrone Aromatase Estradiol 1= β dehydrogenase 5‫و‬4∆ isomerase 2= 17 α hydroxylase , 3= C17,29 lyase 4= 17 β hyroxy estroide dehydrogenase 28 Inactive form of testostrone 29 Testesterone  It is secreted in circulation after synthesis in 5-6 mg /day and 0.3 mg for DHT  It is stored in testis at 20 µ g  Testesterone and DHT are carried in circulation by Carrier proteins  35-65% Testesterone is carried in circulation by Sex hormone binding globulin (SHBG) and a little bit by albumin  SHBG is synthesized in liver and has more affinity for DHT rather than testesterone 30  SHBG synthesis is increased some hepatic disease in hyperthyroidism and  SHBG synthesis is decreased in hypothyroidism androgens and aging , high  97-99% of testesterone is carried in circulation by carrier and 3% is free • Mechanism of Testosterone ( an anabolism hormone) : • Testesterone pass from cell membrane Testostrone + receptor in cytosol H-R H-R enter in nucleus and H bind to DNA (Hormone Response Element (HRE) function • 31 • Testesterone Function • Firstly responsible for the conversion of boys into sexually-mature men • - to induces the overall growth body • - To promote the puberty • To induces the sexual traits and conditions 32