Endocrinology/Objectives/Lecture 4
From PhysioWiki
The hormonal regulation of the female reproductive tract
DESCRIBE the structure and functional compartments of the ovary.
The ovarian compartments are stromal and parenchymal in origin. Stromal tissue includes connective tissue, surface epithelium, and corpora albicans. Parenchymal tissue includes the theca, granulosa, and luteal cells of follicles and corpora lutea.
Theca and granulosa cells are components of follicles, of which there are several types: primordial, primary, secondary, and tertiary (or Graafian) follicles. They are responsible for steroid hormone production. Thecal cells use cholesterol as a precursor for androgens including androstenedione and testosterone. As steroid hormones, these readily diffuse to adjacent granulosa cells, which (via aromatase) convert androgens into estrogens, principally 17-beta-estradiol (but also estrone and estriol).
Luteal cells are derived from theca interna and granulosa cells, forming the theca lutein and granulosa lutein, respectively. They produce estrogen and progesterone, respectively.
LABEL a diagram of ovarian and pituitary hormonal changes during the menstrual cycle.
Okay.
EXPLAIN the differences between estrogen negative and estrogen positive feedback on the hypothalamic-pituitary unit.
Estrogen negative feedback is the normal negative long-loop feedback from peripheral hormones on the hypothalamus and pituitary secretion of GnRH, and gonadotropins (LH, FSH), respectively. In particular, low, non-rising levels of estrogen, estrogen negatively feeds back on the arcuate nucleus of the hypothalamus to inhibit the secretion of GnRH. High levels of estrogen (above 200 pg/ml) for prolonged periods (36 hr) and in a rising phase stimulate the secretion of GnRH by the medial prepoptic nucleus.
DESCRIBE the endometrial events in the menstrual cycle.
Endometrial events include the proliferative and secretory phases, which correspond to the ovarian follicular and luteal phases, respectively. During the proliferative phase, estrogen (principally 17-beta-estradiol secreted by the developing tertiary follicle in the ovary) stimulates proliferation of the endometrial lining. Subsequently, progesterone (secreted by granulosa lutein cells of the corpus luteum) increases the size and secretions (mainly glycoproteins and polysaccharides) of endometrial glands and promotes the lengthening of the spiral arteries. This secretory phase continues as long as progesterone is present.
When progesterone levels decline (as would result from degradation of the corpus luteum into a corpus albicans 10 days after ovulation and without fertilization and implantation), the spiral arteries contract, causing anoxia and subsequent necrosis of the endometrial lining. This necrotic tissue sloughs off, denuding the underlying spiral arteries, producing local hemorrhaging that causes bleeding to aid the washing out of necrotic tissue. (If necrotic tissue were not voided, then it would become a welcome nesting place for bacteria.)
DESCRIBE the steroid precursors of androgens and estrogens.
All androgens and estrogens share cholesterol (endogenous or exogenous) as their common precursor. From cholesterol, granulosa cells synthesize androstenedione and testosterone, which diffuse into the theca where they are converted (by aromatase) into 17-beta-estradiol (and to a lesser extent estrone and estriol).
DISCUSS the selection of the dominant follicle.
A small rise in FSH near days 2-4 of the menstrual cycle select a cohort of 8-10 primordial follicles to become primary follicles. FSH promotes the continued development of these follicles into secondary follicles. In addition to secreting estrogen, these follicles also secrete local inhibitory substances (including androstenedione, testosterone, inhibin) to slow the development of other follicles in the cohort.
Natural variation in the growth rates of these secondary follicles results in one secondary follicle growing faster than the others. This dominant follicle secretes inhibitory substances (and estrogen) in greater amounts, halting the growth of other secondary follicles in the cohort. The dominant secondary follicle then becomes a tertiary (or Graafian) follicle, which secretes high levels of estrogen.
DESCRIBE the effects of estrogen and progesterone on various tissues of the female reproductive tract.
Estrogen
- Stimulates proliferative phase of endometrium
- Negatively feeds back (long-loop) to inhibit GnRH and LH/FSH secretion
Progesterone
- Stimulates secretory phase of endometrium
- Promotes ovulation
- Stimulates collagenases
- Stimulates follicular hyperemia
- Negatively feeds back (long-loop) to inhibit GnRH and LH/FSH secretion (less potent feedback than estrogen's)
DISCUSS the mechanisms of action of oral contraceptives.
Combination oral contraception keeps levels of estrogen and progesterone relatively constant and subthreshold. This maintains estrogen's long-loop negative feedback on LH and FSH secretion (though less so for FSH), which prevents ovulation (no LH surge) and hampers the follicular development (little FSH).
Hormonal levels are too low to promote the proliferative and secretory phases of the endometrium necessary to support implantation of the zygote.
The combination of hormones also thickens the cervical mucus, helping to prevent the entrance of spermatozoa into the uterus, which decreases the probability of fertilization.
DESCRIBE the function of inhibin; where is it synthesized? DESCRIBE the relationship of inhibin to activin.
Inhibin is a polypeptide hormone with significant sequence homology with (but opposing effects compared to) activin. Produced by luteal cells (and elsewhere), inhibin is a selective inhibitor of FSH secretion (and therefore an inhibitor of follicular growth). During the luteal phase, inhibin suppresses the release of FSH from the anterior pituitary. Degeneration of the corpus luteum coincides with a decrease in inhibin secretion, which relieves inhibin's suppression of FSH secretion. This leads to an elevation in FSH levels that promotes the recruitment of another set of 8-10 primordial follicles, beginning a new iteration through the cycle.
DISCUSS the causes of amenorrhea and name disease states in which amenorrhea occur.
Causes
- High progesterone levels (eg, during pregnancy, lactation)
- Decreased FSH
- Low GnRH
Disease states
- Polycystic ovarian syndrome (elevated LH, depressed FSH, increased androgens)
- Stress; eg, anorexia nervosa (CRH and beta-endorphins depress GnRH release)
