Gonad Hormones : Female

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Gonad Hormones : Female. Prof.Dr .Glden Burak 2011-2012. Ovary : produces female sex hormones and female germ cells. The ovarian follicles are of two functional types; nongrowing ( primordial) and growing Primordial follicles degenerate (atresia) - PowerPoint PPT Presentation

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  • Gonad Hormones : FemaleProf.Dr.Glden Burak2011-2012

  • Ovary : produces female sex hormones and female germ cells

  • The ovarian follicles are of two functional types; nongrowing ( primordial) and growing Primordial follicles degenerate (atresia)Mature ovarian follicle (graafian) consists three layers of cells : theca externa, theca interna and granulosaThe oocyte is contained within the follicular fluidAfter rupture of the mature follicle and release of the ovum, granulosa and theca cells proliferate to form the corpus luteum.Corpus luteum is a transient endocrine organ

  • Hypothalamic-Pituitary-Ovarian AxisConstant pulsatile release of GnRH from the hypothalamusSynthesis, storage and secretion of gonadotropins (FSH and LH) from the anterior pituitary (-/+)Feedback relationships between the ovarian hormones (estradiol,progesterone) , GnRH, FSH and LH secretionsCyclical ovarian function

  • (+) Feedback of gonadal steroids on pituitaryE2 > 700 pmol/L,maintenance of elevated levels for at least 48 hoursProgesterone, only after the pituitary has been exposed to prolonged high levels of E2 Chronic stress or profound weight loss can disrupt the pattern of GnRH secretion and lead to anovulation and amenorrhea.

  • In childhood : HPA remains highly sensitive to (-) feedback effects of gonadal steroidsIn puberty : adrenarche, decreased sensitivity of HPA to (-) feedback and gonadarche, increased E2, onset of ovulatory cyclesandrostenedione,DHEA, DHEAS: 6-8 yearspulsatile secretion of GnRH is critical in the initiation of puberty.in girls FSH increases earlier than LH

  • Ovarian steroid hormonesEstrogens C18 (Granulosa)17 -EstradiolEstrone : post-menopauseEstriol : in pregnancyProgestagens C21 (Corpus Luteum) Pregnenolone Progesterone 17 OH ProgesteroneAndrogens C19 (Theca) DHEA, androstendione, testosterone, dihydrotestosterone

  • Aromatization of androgens in granulosa cells (also some estradiol in corpus luteum)Three hydroxylation steps, O2 and NADPHP450 mixed-function oxidaseTestosterone estradiolAndrostendione estronePeripheral aromatization of androgensAdrenal androgens : DHEA (major but weak), androstendione (potent) Conversion : 3-hydroxy steroid dehydrogenase,5,4 isomeraseDuring pregnancy and post-menopausal period In adipose cells, liver, skin and other tissuesIncreased aromatase activity , estrogenization in cirrhosis,hyperthyroidism, aging and obesity

  • Ovarian nonsteroidal hormonesCytokines, growth factors and neuropeptidesInhibins : multifunctional glycoproteins A and BInhibin A(A) is low in early follicular phase, high in the luteal phase ;inhibin B(B) parallels FSHInhibin B synthesized in granulosa cells and inhibin A in corpus luteum cells. increase theca cell androgen productionOvarian-pituitary negative feedback relationshipsActivins : disulfide-linked dimers of the -subunits of inhibin.Activin A produced in the ovary augments the effects of FSHActivin B produced in the gonadotropes increases FSH secretion

  • 60% loosely bound to albumin (>3000mg/L)38% bound with high affinity to SHBG % 2-3 is free Progesterone binds strongly to CBG and weakly to albumin The binding proteins provide a circulating reservoir of hormoneThe metabolic clearance rates are inversely related to SHBG affinityConjugated derivatives are not bound

  • SHBG synthesis in hepatocytesIncreased by thyroid hormones, estrogens (5-10x),decreased levels of androgens,high carbohydrate diet, stress, aging, cirrhosis.Decreased by androgens (2x) hyperprolactinemia, increased growth hormone, obesity, menopause, progestins, glucocorticoids. The normal level of SHBG is about 30-50% lower in men than in women.

  • Metabolism of ovarian steroidsIn the liver,estradiol (E2) and estrone(E1 ) are converted to estriol (E3) and conjugated with glucuronic a. or sulfate; excreted by the kidneyOral estrogens are effective because the activity of conjugating enzymes are lowProgesterone is converted to pregnanediol, conjugated (sodium pregnanediol-20 glucuronide) and excreted by the kidneySome synthetic steroids have progestational activity and avoid hepatic metabolism;used as contraceptives

  • EstrogensMaturation of primordial germ cellsProvision of the hormonal timing for ovulationDeveloping the tissues that will allow for implantation of the blastocytEstablishment of the milieu required for the maintenance of pregnancy Provision of the hormonal influences for parturition and lactationAnabolic effects on bone and cartilageVasodilation and heat dissipation

  • Progestinsgenerally require the previous or concurrent presence of estrogensreduce the proliferative activity of the estrogens on the vaginal epitheliumconvert the uterine epithelium from proliferative to secretory ; preparing it for implantation of the fertilized ovum.enhance the development of the acinar portions of breast glands after estrogens have stimulated ductal development.decrease peripheral blood flow, decrease heat loss

  • Menstrual cycle-Follicular phaseA particular follicle begins to enlarge under the influence of FSH E2 and LH rise, E2 reaches its max. level 24 hours before the LH (FSH) peak and sensitizes the pituitary to GnRH LH peak heralds the end of the follicular phase and precedes ovulation by 16-18 hours.Follicle rupture ,releasing an ovaContinual administration of high doses of estrogen (oral contraceptives) supresses LH and FSH release and inhibits the action of GnRH on the pituitary

  • Menstrual cycle-Luteal phaseThe granulosa cells of the ruptured follicle luteinize and form the corpus luteumCorpus luteum produces progesterone and some E2Estradiol peaks about midway through the luteal phase and then declines to a very low level.The major hormone is progesteroneLH is required for the early maintenance of the corpus luteum and the pituitary supplies it for 10days. If implantation occurs LH function is assumed by hCGhCG stimulates progesterone synthesis by corpus luteum until placenta begins to make in large amountsIn the absence of implantation corpus luteum regresses causing a decrease in progesterone.

  • Placental hormones maintain pregnancyHuman chorionic gonadotropin hCGstructurally similar to LHsupports corpus luteum until placenta produces sufficient amounts of progesteroneProgestins6-8 weeks : corpus luteum produces progesteronethereafter : placenta produces progesterone (30-40 times more)Placenta does not synthesize cholesterol and depends on maternal supplyEstrogens E1, E2, E3The major hormone is E3 synthesized by feto-placental functionPlacental lactogen (PL): chorionic somatomammotropin/ placental growth hormone

  • Steroid metabolism by the fetal-maternal unit

  • Mammary gland developmentE2 (for ductal growth)Progesterone (alveolar proliferation)Additional actions of prolactin, glucocorticoids, insulinProgesterone inhibits milk production and secretion in late pregnancyLactation : prolactin and oxytocinThe production of oxytocin and its receptors are stimulated by estrogens and inhibited by progesterone

  • MenopauseWeak estrogen ,E1, produced by aromatization of androstenedioneMarked increases of LH and FSHEstrone is not always able to prevent the atrophy of secondary sex tissues and osteoporosis

  • Pathological StatesHypogonadismGonadal dysgenesisPolycystic ovary syndrome : overproduction of androgens ( hirsutism, obesity,irregular menses,impaired fertility)HypergonadismGranulosa-theca cell tumorsPersistent trophoblastic tissue : benign hydatiform mole and its malignant form , choriocarcinomaInfertilityElevated testosterone,decreased SHBGDHEA sulphate :adrenal ;androstenedione : ovary

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