Control Of Follicle-stimulating Hormone Secretion Research Articles

From Menarche to Regular Menstruation

Marked changes in hormone secretion occur from childhood to adulthood. Prior to puberty gonadotropin-releasing hormone (GnRH) secretion is markedly suppressed. At the onset of puberty, the hypothalamic gonadostat is derepressed and the amplitude of GnRH pulses increases. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels increase gradually during puberty stimulating follicle maturation and estrogen production in the ovaries. Only the negative feedback mechanism is powerful before puberty, while the positive feedback mechanism becomes active for the first time in late puberty. As a result, normal cyclicity is usually established at that time. During normal menstrual cycle, steroidal and nonsteroidal hormones mediate the effect of the ovaries on the hypothalamic-pituitary system. Estradiol and progesterone are important regulators of FSH and LH secretion, while inhibins play a role in the control of FSH secretion. Gonadotropin surge attenuating factor (GnSAF) is a nonsteroidal ovarian substance that controls the amplitude of the midcycle LH surge by antagonizing the sensitizing effect of estradiol on the pituitary.

Ovarian regulators of gonadotropin secretion.

Great progress in the ovarian mechanisms that control gonadotrophin secretion in women has recently been achieved. Estradiol (E2) is the main component of the ovarian negative effect on basal gonadotropin secretion during the normal menstrual cycle. However, nonsteroidal substances such as inhibins and activins that can affect follicle-stimulating hormone (FSH) secretion in vitro may also participate in the control of FSH secretion in vivo. Recent evidence has shown that the ovaries also produce another nonsteroidal substance, named gonadotropin surge-attenuating factor (GnSAF), that specifically attenuates GnRH-induced LH secretion and the endogenous LH surge in superovulated women. It is possible that during the normal menstrual cycle GnSAF controls the amplitude of the midcycle LH surge by antagonizing the stimulating effect of E2 on the pituitary.

Effects of passive immunization against oestradiol-17beta and inhibin on the secretion of gonadotrophin in the cyclic golden hamster (Mesocricetus auratus).

To investigate the physiological importance of oestradiol-17beta and inhibin in the regulation of gonadotrophin secretion in the cyclic golden hamster, females were passively immunized against two hormones. When 200 microL antiserum against oestradiol-17beta (oestradiol-AS) was given on Day 3 (Day 1 = day of ovulation), the preovulatory gonadotrophin surge was completely blocked for 24 h and the length of the oestrous cycle was also prolonged for one day. In the group given 200 microL oestradiol-AS on Day 3, basal levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) increased slightly and superovulation (19.6+/-0.8, mean+/-s.e.m.) occurred. When 200 microL antiserum against inhibin (inhibin-AS) was given at 1100 hours on Day 3, a dramatic increase in plasma FSH and a slight increase in LH were noted, resulting in superovulation (38.2+/-2.6) on the expected Day 1. The present study indicates clearly that inhibin plays a major role in regulating the specific ovulation rate in the hamster through the control of FSH secretion. Present results also indicate that oestradiol-17beta suppresses basal LH secretion. Oestradiol-17beta may act as an indicator of the follicular maturation, and the high plasma concentration of oestradiol-17beta noted from Day 3 to Day 4 may play an important role in determining the timing of initiation of the preovulatory gonadotrophin surge.

Inhibin-mediated feedback control of follicle-stimulating hormone secretion in the female rat.

The secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland is regulated by the interaction of hypothalamic and gonadal hormones. Recently, proteins termed inhibins that selectively suppress FSH secretion have been purified and characterized from the gonadal fluids of several species. Antibodies to a synthetic peptide encompassing the amino terminal 25 residues of the recently characterized porcine inhibin were used to develop a specific radioimmunoassay (RIA) for inhibin and to neutralize endogenous inhibin during the estrous cycle of the rat. The administration of 20 international units of pregnant mare serum gonadotropin (PMSG) stimulated the secretion of inhibin in intact immature female rats, whereas ovariectomy caused an abrupt decrease in plasma inhibin concentrations that were not prevented by the injection of PMSG. The infusion of a polyclonal antiserum to inhibin, from 12 noon on proestrus to 1 a.m. on the morning of estrus, as well as its acute intravenous injection during diestrus I or II, caused an increase in plasma FSH (but not luteinizing hormone) concentrations. These results support the hypothesis of a feedback loop between the release of ovarian inhibin and FSH in the female rat.

A role for inhibin in the control of follicle-stimulating hormone secretion in male rats.

We examined the relationship of testosterone (T) and porcine follicular fluid (pFF) in the negative feedback control of FSH and LH secretion in adult male rats. Either at the time of castration (acute) or at least 30 days after castration (chronic), we implanted T-filled Silastic capsules, which were 2 mm, 10 mm, or 30 mm long; empty capsules (30 mm) served as controls. Seven days later, we injected either 0.15 ml of pFF or saline (i.v.), decapitated the rats 6 hours later, and collected trunk blood for subsequent serum analysis of FSH, LH, and T by RIA. In the acute groups, T implants suppressed the postcastration rises in plasma FSH and LH levels in a dose-dependent manner, with only the largest implant, 30 mm, able to return them to intact levels. PFF injection significantly suppressed FSH levels in intact and acute rats but had no effect on serum LH. In chronic rats, T therapy for 7 days suppressed plasma LH levels in a dose-dependent relationship, yet did not do so to plasma FSH levels. FSH levels were significantly higher in rats with the 30 mm T implants than in intact rats, but were significantly suppressed as compared to chronic controls. PFF significantly suppressed serum FSH levels in all chronic groups with the chronic controls showing the greatest amount of suppression. We conclude that the role for inhibin in the normal control of FSH secretion is that of a secondary modulator which is superimposed on, yet independent of, the steroid feedback mechanism. At any given moment this modulation is dependent upon the secretory activity of the FSH gonadotrope.

Control of follicle-stimulating hormone secretion by steroid-free bovine follicular fluid in the ovariectomized rat.

The effects of steroid-free bovine follicular fluid (bFF) and sodium phenobarbitone on spontaneous LH releasing hormone (LHRH)-induced secretion of FSH and LH were studied in ovariectomized rats. Luteinizing hormone releasing hormone was administered by infusion to rats anaesthetized with phenobarbitone. Bovine follicular fluid reduced FSH release and synthesis. Luteinizing hormone release remained unaffected after bFF treatment. Phenobarbitone reduced both FSH and LH release. The observed suppressive effects of bFF and phenobarbitone on FSH secretion were additive, suggesting that the basal release of FSH has an LHRH-dependent and an LHRH-independent component. Furthermore, bFF did not affect pituitary responsiveness of LH secretion to LHRH and reduced the responsiveness of FSH secretion only when administered some time before the LHRH challenge. The present observations support the view that in the ovariectomized rat the pituitary gland is the only site of action of inhibin-like activity as present in bFF.

Possible role of 5 alpha-androstane-3 alpha, 17 beta-diol in the control of follicle-stimulating hormone secretion in the immature female rat.

A possible role of 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-androstanediol) in the control of FSH secretion was studied at various ages in ovariectomized rats. In the rat strain used, vaginal opening, coincident with first ovulation, generally occurs between 37 and 42 days of age. If 3 alpha-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 microgram/100 g body wt) between 13 and 30 days of age; at 33-35 days of age only the 300 microgram dose caused some inhibition of FSH release. Results were more complex if 3 alpha-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3 alpha-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3 alpha-androstanediol was combined with oestradiol a clear decrease in effect, as compared to the effect of oestradiol alone, was found between 20 and 30 days of age. Also the effect of combined oestradiol and progesterone treatment was greater than the effect of combined treatment with oestradiol, progesterone and 3 alpha-androstanediol. At all ages after day 20 none of the steroid combinations tested was capable of maintaining FSH levels in ovariectomized rats similar to those in intact rats. It is concluded that 3 alpha-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3 alpha androstanediol on FSH secretion is limited in the presence of oestradiol.

Problems in contraception.

Earlier projections of birth rate were erroneous because of inadequate appreciation of the many and changing variables: rates of industrialization, educational levels, changes in economic activity, rates of family formation, marriage, timing of births, and so forth. Although a decline in fertility may be projected over the next few years, the rising proportion of women of child-bearing age will result in higher birth rates. Many women still have more children than they say they want, and family planning has been accepted by most American women. Although only a few women receiving oral contraceptives become hypertensive, almost all women show an increase in plasma renin activity, plasma renin substrate, and angiotensin II. Hemodynamic studies show small but consistent. increases in cardiac output and mean arterial blood pressure. The oral contraceptives have been associated with an increased risk of thromboembolic disorders and death from pulmonary embolism. The relative risk of venous thromboembolism increases with increasing dose of estrogen, leading to the recommendation that the oral contraceptives contain no more than 50 µg of mestranol or ethinyl estradiol. Survey of the processes in sperm and ovum maturation and fertilization shows many areas where other approaches to contraception may be fruitful. These include several areas of basic scientific interest: the meiotic stage of spermatogenesis, the control of follicle-stimulating hormone secretion, regulation of corpus-luteum life span and steroid synthesis, and the role of progesterone in maintaining a secretory endometrium.