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nongrowing ( primordial) and growing Primordial follicles degenerate (atresia) Mature ovarian follicle (graafian) consists three layers of cells : theca externa, theca interna and granulosa The oocyte is contained within the follicular fluid After 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 Axis
Constant pulsatile release of GnRH from the hypothalamus Synthesis, storage and secretion of gonadotropins (FSH and LH) from the anterior pituitary (-/+)Feedback relationships between the ovarian hormones (estradiol,progesterone) , GnRH, FSH and LH secretions Cyclical ovarian function
E2 > 700 pmol/L,maintenance of elevated levels for at least 48 hours Progesterone, 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 steroids In puberty : adrenarche, decreased sensitivity of HPA to (-) feedback and gonadarche, increased E2, onset of ovulatory cycles androstenedione,DHEA, DHEAS: 6-8 years pulsatile secretion of GnRH is critical in the initiation of puberty. in girls FSH increases earlier than LH
Aromatization of androgens in granulosa cells (also some estradiol in corpus luteum) Three hydroxylation steps, O2 and NADPH P450 mixed-function oxidase Testosterone estradiol Androstendione estrone Peripheral aromatization of androgens Adrenal androgens : DHEA (major but weak), androstendione (potent) Conversion : 3-hydroxy steroid dehydrogenase,5,4 isomerase During pregnancy and post-menopausal period In adipose cells, liver, skin and other tissues Increased aromatase activity , estrogenization in cirrhosis,hyperthyroidism, aging and obesity
Cytokines, growth factors and neuropeptides Inhibins : multifunctional glycoproteins A and B Inhibin A(A) is low in early follicular phase, high in the luteal phase ;inhibin B(B) parallels FSH Inhibin B synthesized in granulosa cells and inhibin A in corpus luteum cells. increase theca cell androgen production Ovarian-pituitary negative feedback relationships Activins : disulfide-linked dimers of the -subunits of inhibin. Activin A produced in the ovary augments the effects of FSH Activin 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 hormone The metabolic clearance rates are inversely related to SHBG affinity Conjugated derivatives are not bound
Estrogens
Maturation of primordial germ cells Provision of the hormonal timing for ovulation Developing the tissues that will allow for implantation of the blastocyt Establishment of the milieu required for the maintenance of pregnancy Provision of the hormonal influences for parturition and lactation Anabolic effects on bone and cartilage Vasodilation and heat dissipation
Progestins
generally require the previous or concurrent presence of estrogens reduce the proliferative activity of the estrogens on the vaginal epithelium convert 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
A 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 ova Continual administration of high doses of estrogen (oral contraceptives) supresses LH and FSH release and inhibits the action of GnRH on the pituitary
Human chorionic gonadotropin hCG structurally similar to LH supports corpus luteum until placenta produces sufficient amounts of progesterone Progestins 6-8 weeks : corpus luteum produces progesterone thereafter : placenta produces progesterone (30-40 times more) Placenta does not synthesize cholesterol and depends on maternal supply Estrogens E1, E2, E3 The major hormone is E3 synthesized by feto-placental function Placental lactogen (PL): chorionic somatomammotropin/ placental growth hormone
E2 (for ductal growth) Progesterone (alveolar proliferation) Additional actions of prolactin, glucocorticoids, insulin Progesterone inhibits milk production and secretion in late pregnancy Lactation : prolactin and oxytocin The production of oxytocin and its receptors are stimulated by estrogens and inhibited by progesterone
Menopause
Weak estrogen ,E1, produced by aromatization of androstenedione Marked increases of LH and FSH Estrone is not always able to prevent the atrophy of secondary sex tissues and osteoporosis
Pathological States
Hypogonadism Gonadal dysgenesis Polycystic ovary syndrome : overproduction of androgens ( hirsutism, obesity,irregular menses,impaired fertility) Hypergonadism Granulosa-theca cell tumors Persistent trophoblastic tissue : benign hydatiform mole and its malignant form , choriocarcinoma Infertility Elevated testosterone,decreased SHBG
DHEA sulphate :adrenal ;androstenedione : ovary