No abstract

When it was initially discovered in 1923, inhibin was characterized as a hypophysiotropic hormone that acts on pituitary cells to regulate pituitary hormone secretion. Ninety years later, what we know about inhibin stretches far beyond its well-established capacity to inhibit activin signaling and suppress pituitary FSH production. Inhibin is one of the major reproductive hormones involved in the regulation of folliculogenesis and steroidogenesis. Although the physiological role of inhibin as an activin antagonist in other organ systems is not as well defined as it is in the pituitary-gonadal axis, inhibin also modulates biological processes in other organs through paracrine, autocrine, and/or endocrine mechanisms. Inhibin and components of its signaling pathway are expressed in many organs. Diagnostically, inhibin is used for prenatal screening of Down syndrome as part of the quadruple test and as a biochemical marker in the assessment of ovarian reserve. In this review, we provide a comprehensive summary of our current understanding of the biological role of inhibin, its relationship with activin, its signaling mechanisms, and its potential value as a diagnostic marker for reproductive function and pregnancy-associated conditions.

The alterations in morphology and function of the ovarian follicle as it matures, ovulates, and becomes a corpus luteum are dramatic. A variety of steroid and polypeptide hormones influence these processes, and the ovary in turn produces specific hormonal signals for endocrine regulation. One such signal is inhibin, a heterodimeric protein that suppresses the secretion of follicle-stimulating hormone from pituitary gonadotrophs. Rat inhibin complementary DNA probes have been used to examine the levels and distribution of inhibin alpha-and beta A-subunit messenger RNAs in the ovaries of cycling animals. Striking, dynamic changes have been found in inhibin messenger RNA accumulation during the developmental maturation of the ovarian follicle.

Preovulatory GnRH and LH surges depend on activation of estrogen (E 2 )-inducible progesterone receptors (PGRs) in the preoptic area (POA). Surges do not occur in males, or in perinatally androgenized females. We sought to determine whether prenatal androgen exposure suppresses basal or E 2 -induced Pgr mRNA expression or E 2 -induced LH surges (or both) in adulthood, and whether any such effects may be mediated by androgen receptor activation. We also assessed whether prenatal androgens alter subsequent GnRH pulsatility. Pregnant rats received testosterone or vehicle daily on Embryonic Days 16-19. POA-hypothalamic tissues were obtained in adulthood for PgrA and PgrB (PgrA؉B) mRNA analysis. Females that had prenatal exposure to testosterone (pT) displayed reduced PgrA؉B mRNA levels (P Ͻ 0.01) compared with those that had prenatal exposure to vehicle (pV). Additional pregnant animals were treated with vehicle or testosterone, or with 5␣-dihydrotestosterone (DHT). In adult ovariectomized offspring, estradiol benzoate produced a 2-fold increase (P Ͻ 0.05) in PgrA؉B expression in the POA of pV females, but not in pT females or those that had prenatal exposure to DHT (pDHT). Prenatal testosterone and DHT exposure also prevented estradiol benzoate-induced LH surges observed in pV rats. Blood sampling of ovariectomized rats revealed increased LH pulse frequency in pDHT versus pV females (P Ͻ 0.05). Our findings support the hypothesis that prenatal androgen receptor activation can contribute to the permanent defeminization of the GnRH neurosecretory system, rendering it incapable of initiating GnRH surges, while accelerating basal GnRH pulse generator activity in adulthood. We propose that the effects of prenatal androgen receptor activation on GnRH neurosecretion are mediated in part via permanent impairment of E 2 -induced PgrA؉B gene expression in the POA.

The binding of [6-alanine]gonadotropin-releasing hormone to pituitary plasma membranes increased threefold between metestrus and early proestrus in female rats. Receptor numbers fell rapidly on the afternoon of proestrus coincident with the preovulatory gonadotropin surge. The numbers of receptors for gonadotropin-releasing hormone were positively correlated with concentrations of estradiol in serum; this pattern may be a necessary component of increased pituitary sensitivty to gonadotropin-releasing hormone observed during proestrus.

No abstract

In the cyclic rat, uterine weight increases at proestrus, pituitary LH content drops from a maximum at proestrus to a minimum at estrus, and ovulation and vaginal cornification then occur. To investigate the timing of the ovarian secretion presumably responsible for these changes, ovariectomy or sham ovariectomy was performed at increasing intervals before the day of estrus. Results in both 4- and 5-day cyclers indicate that the ovary must be in situ between diestrus 4 pm (day before proestrus) and proestrus 10 am in order for estrous vaginal cornification to occur; it must be in situ between diestrus 10 am and 4 pm (day before proestrus) for the uterine weight increase and pituitary LH discharge to occur. In some rats sham ovariectomy, when performed at diestrus 10 am, delayed the proestrous-estrous changes by at least 24 hr. The "extra" day which occurs in normal 5-day cycles results at least partly from a delay in the steroid discharge necessary to cause release of the ovulating surge of LH.

Margoliash, September 20, 1977 ABSTRACT The present studies were carried out to see if porcine follicular fluid could inhibit increases in serum follicle stimulating hormone (FSH) levels when injected into the rat. For these studies the pentobarbital-treated proestrous rat was chosen as the major test animal model. If an artificial surge of luteinizing hormone (LH) is administered to these rats, it can induce a synchronized secondary rise in FSH secretion rate. Normal saline-treated rats were also used as test animals. They exhibit preovulatory endogenous "surges" of LH and FSH, and also a secondary FSH rise.Porcine follicular fluid was harvested from medium-sized and large (3-to 10-mm diameter) follicles and treated with charcoal to remove endogenous steroids. Charcoal-treated porcine serum served as a control solution. The fluid was injected intraperitoneally in two 0.5-ml doses into pentobarbital-treated proestrous rats immediately and 3 hr after LH injection. Follicular fluid, but not the serum, suppressed the secondary, LH-induced FSH rise (P < 0.01) in a dose-dependent manner, without altering the effects of LH upon serum ovarian steroid levels or follicular rupture. It was effective down to a total dose of 200 Al. Porcine follicular fluid also blocked the secondary FSH surge in normal proestrous rats exhibiting endogenous LH/FSH primary surges. Thus, it would appear that porcine follicular fluid contains a non-steroidal substance~s) that can block the secretion of FSH that is secondary to a natural or artificial LH surge.