The sixth batch of Mansoura Manchester programme

The sixth batch of Mansoura Manchester programme
Professor: Alaa Mosbah , Mansoura Manchester programme

Friday, December 28, 2007

Physiology of Reproduction

1-Hypothalamus -It lies at the base of the brain just above the junction of optic nerves -It contains many nuclei including (Supraoptic, paraventricular & arcuate nuclei) -It secrets both releasing & inhibiting hormones *Hypothalamic releasing factors 1-Gonadotrophin releasing hormone (LHRH or Gn RH), it consists of 10 amino acids 2-Thyrotophin releasing hormone (TRH), it consists of 3 amino acids 3-Corticotrophin releasing hormone (CRH), it consists of 41 amino acids 4-Growth hormone releasing hormone, it consists of 40 amino acids *Hypothalamic inhibiting factors 1-Growth hormone inhibiting hormone, it consists of 14 amino acids 2-Prolactin inhibiting factor (Dopamine) Functions of the hypothalamus 1-Regulation of the primitive functions needed for survival as (Appetite control, temperature control, salt & water retention, metabolism & growth) 2-Control of reproduction, it acts as a transducer to convert neuronal pulses into release of GnRH Gonadotrophin releasing hormone -It is a decapeptide (10 amino acids) -Secreted by the preoptic & arcuate nuclei in pulses every 60-90 minutes -Passes in the hypophyseal portal circulation to reach the anterior pituitary ----- secretion of FSH & LH -Half life ---- 2-4 minutes -Decreased GnRH pulse frequency is associated with oligomenorrhea or amenorrhea -Increased GnRH pulse frequency is associated with PCOD Control of GnRH Pulses 1-Dopamine ---- decrease the pulse frequency 2-Endogenous opioid ---- inhibit the pulse frequency 3-Neuropeptide Y ----- stimulate the pulse frequency 4-Noreoinephrine ------ stimulate the pulse frequency II-Pitutary gland -It consists of anterior lobe (adenohypophysis) & the posterior lobe (neurohypothesis) -The adult pituitary measure 13 x 10 x 6 mm & weighs 0.5 gm -The anterior pituitary secretes: gonadotronhins (FSH & LH), & prolactin 1-Follicle stimulating hormone (FSH) -It is a water soluble glycoproteins, consists of α-subunit (92 amino acids) & β- subunit (118 amino acids) -Secreted by the basophilic cells -Begins to be secreted at the end of the previous cycle, reaching a peak at day 3 o the new cycle, then the level falls & again it rises to reach a second peak at the 13th day just before ovulation -Half life --- 3-4 hours -Actions of FSH 1-Stimulate growth, ripening & maturation of the ovarian follicles 2-Stimulate aromatase activity in the granulosa cells 3-In combination with LH, it results in ovulation 4-Stimulate the formation of LH receptors 2-Luteinizing hormone (LH) -It is a water soluble glycoprotein, consists of α- subunit (92 amino acids) & β- subunit (121 amino acids) -Secreted by the basophilic cells -LH level: It is fairly constant throughout the cycle & reaches a peak about the 13th day -Half life --- 20 minutes Actions of LH -In combination with FSH it promotes ripening of the follicles -The LH surge ----- rupture of the mature follicle & ovulation -Stimulate corpus luteum to secrete estrogen & progesterone 3-Prolactin -Polypeptide hormone (191 amino acids) -Secreted by the lactotrophs (acidophilic cells) -It is the only anterior anterior pitutary hormone controlled by hypothalamic inhibiting factor (Dopamine) Actions of prolactin 1-Lactation 2-High levels inhibit estrogen secretion by the ovary 3-Essential for corpus luteum function 4-Control of ovulation by preventing further ovulation after fertilization Hypothalamic-Pituitary-Ovarian Axis -Hypothalamus releases GnRH to & passes via the hypophyseal portal circulation & act on gonadotrophin receptors in the anterior pituitary cells resulting in cyclic release of FSH & LH -Secretions of the hypothalamic GnRH is influenced by negative feed- back effect of estrogen & progesterone -FSH stimulate the growth of primary follicles & only one predominate to form mature follicle & secrete increasing amounts of estrogen ----- estrogen peak----- stimulate the anterior pituitary to secrete LH (positive feed back) -LH surge will lead to ovulation & formation of corpus luteum that secretes estrogen & progesterone -This high estrogen level will lead to suppression of Gn.RH (negative feed back) ----- low LH levels & degeneration of corpus luteum resulting in menstruation Types of feed back mechanisms 1-Long loop feed back (may be positive or negative) -The effect of the target organ hormones (estrogens & progesterone) on the hypothalamus & pituitary 2-Short loop feed back -The pituitary trophic hormones ---- suppression of the hypothalamic releasing factors 3-Ultra short loop feed back -Autocrine & paracrine effects of GnRH on the gonadotropin secreting cells in the hypothalamic nuclei Ovaries The ovaries has two functions: 1-Production of ova (ovarian cycle) 2-Endocrine function ----- production of estrogens & progesterone -The length of the ovarian cycle range from 21-35 days -The ovarian cycle is composed of (follicular & luteal) separated by ovulation 1- Follicular phase -The phase of ripening of the ovum -Begins on the first day of menstruation & occupies the first 14 days -Under the effect of FSH, 50 or more follicles start to ripen, one of these ova outstrips the rest and matures, dominant follicle), while the others undergo atresia -During the process of ripening, the mature Graffian follicle makes its way towards the ovarian surface to bring the discus proligerus with the ovum under the peritoneum The mature Graffian follicle -Size ---- 12-24 mm -Structure ---- composed of: 1-Ovum 2-Perivitelline space surrounds the ovum 3-Zona pellucida surrounds the perivitelline space. 4-Corona radiata: granulosa cells arranged in rows surrounding the ovum and attached to the zona by fine cytoplasmic processes 5-Cumulus oophorus (discus proligerus): Group of granulosa cells that attach the corona radiata to the wall of the follicle 6-Granulosa cells that lines the inner wall of the follicle & surround the follicular space that is filled with liquor folliculi 7-Theca interna cells spindle shaped cells 8-Theca externa cells --- Stroma cells that are compressed & modified to from a false capsule Ovulation Definition ----- rupture of the mature Graffian follicle with escape of the ovum surrounded by corona radiata through a stigma in the follicular wall into the peritoneal cavity & is picked up by the fimbrae of the fallopian tube Mechanism of ovulation *Central mechanism due to LH surge *Peripheral mechanisms 1-Thinning & degeneration of the cyst wall due to the action of proteases 2-Contraction of micromuscle cells in the theca externa & the stroma (due to PG in the follicular fluid) 3-Increased intrafollicular tension due to increase in the fluid content 2- Luteal phase -The phase of formation, function & early degeneration of the corpus luteum -Duration of the luteal phase is more constant than the follicular phase -Duration is said to be 14 + 2 day *Stages of corpus luteum formation 1- Stage of Proliferation 2-Vascularization: new blood vessels invade the follicle through the site of rupture 3-Maturity: the corpus luteum is functioning with maximum activity after 5 days for 3-4 days 4-Degeneration: occur 4-6 days before the next menstrual period ---- corpus albicans & results in low estrogen and progesterone levels & menstruation Corpus luteum of pregnancy The troplablast secrete human chorionic gonadotrophins within 7 days that prevents degeneration of corpus luteum & continues to produce estrogen & progesterone ---- suppression of anterior pituitary gland & the ovarian cycle Corpus fibrosum or atreticum The primary oocytes that do not mature will disappear at menopause or soon after 1-If the oocyte is blighted at an early stage the primordial follicle is obliterated & replaced by connective tissue 2-If there is some ripening -The oocyte will disintegrate by pyknosis & chromatolysis -A small cyst is formed lined with granulosa cells surrounded by theca lutein cells Causes of follicular atresia 1-Secretion of inhibitory peptide that impairs the binding of LH receptors 2-Inhibition of FSH by negative feed back from: (Estrogen & inhibin hormone) Ovarian Hormones I- Estrogens Sources --- produced by: 1-Ovary from (Graffian follicle & Corpus luteum) 2-Adrenal cortex (small amounts) 3-Placenta Metabolism: in the liver by conjugation with glucouronide or sulphate group, excreted in feces & urine Synthesis of estrogen (Two cell theory) 1-LH acts on the theca cells to produce androgens (androstendione & testosterone ) 2-Androgens diffuses from the theca cells to the granulosa cells 3-FSH stimulates aromatase enzyme to estrogens (estradiol E2 & estriol E3) Levels (2 peaks) -First peak before ovulation (about 300 pg/ml), then it falls -Second peak in the midluteal phase (about 200 pg/ml). then decrease when corpus luteum degenerates Biological actions of estrogen 1-General effects -Appearance of secondary sex characters at puberty -On the breast: it increase the duct system & vascularity -On bones stimulates osteoblastic activity & union of epiphysis -Salt & water retention 2-Central effects (On hypothalamus & pituitary), large dose inhibits FSH release 3-Actions on the genital tract @-On the uterus -Increased vascularity -Endometrium undergo proliferation & hyperplasia -Myometrium undergo hypertrophy & increased sensitivity to oxytocin @-On the cervix -Increase the volume of cervical mucus (water & salt content) -Positive spinabarkeit -Positive Fern test @-On the vagina -Epithelial lining: proliferation & increased glycogen deposition -Increased vaginal acidity due to conversion of glycogen into lactic acid 2-Progesterone Sources 1-Ovary ( corpus luteum), 2-Placenta Metabolism in the liver & 20% is excreted in urine as pregnanediol Levels -Progesterone level starts to rise just before ovulation -Reaches a peak in the mid luteal phase (15 ng/ml) & then drops gradually before menstruation Biological effects of progesterone 1- General actions 1-Increases the basal body temperature (thermogenic) 2-Salt & water retention 3-Relaxes smooth muscles 4-On the breast: development of alveolar system 2- Central action -Large doses inhibit LH secretion 3-On the genital tract *On the uterus 1- Endometrium: induces secretory changes in an estrogen primed endometrium 2-Myometrium -- uterine contractions become frequent but of high amplitude 3-Isthmus ----- Constriction *On the Cervix -The mucus becomes more viscid with negative sptinnbarkeit & negative fern test Menstrual Cycle 1-Menstrual phase Duration ----- 3-7 days -Scattered small areas of the endometrium are necrosed & are shed off at alternative times. then the whole endometrium is cast off except the deep compact layer -At the end of menstruation, the basal part of the glands start to grow and form new glands 2-Resting phase -Duration: 1-2 days following menstruation -Thickness of endometrium: 1-2 mm -Glands: simple tubular scattered widely in the stroma -Epithelium: cubical ciliated epithelium which dips down to from glands. -Stroma: small spindle shaped connective times cells with little cytoplasm 3-Proliferative phase -Duration: 9-10 days -Glands: tubular, increase in length & dilatation more numerous -Epithelium: more columnar with central nuclei. -Stroma cells are more globular & increase in size & vascularity 4-Secretory phase (Under the effects of progesterone & estrogens) -Duration: 12-14 day (from ovulation till menstruation) -Thickness: 5-7 mm -Glands: more tortous corkscrew, distended with secretions -Stroma: shows dense leucocytic infiltration 2-3 day before menstruation. The stroma cells become more polygonal & increase in size -Differentiated into 3 layers: (superficial compact zone, Middle spongy layer & Deep compact layer)

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