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In order to determine whether treatment of endocrinologically normal women with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) led to alternations in follicular fluid inhibin activity and steroids, both inhibin activity and steroid levels were measured in follicular fluid of 10 follicles of 9 women treated with hMG/hCG and in follicular fluid of 15 preovulatory follicles of 15 untreated women. The women were given 150 IU hMG daily from day 3 until the serum estrogen levels were > 300 pg/ml, at which time hMG was discontinued and 10,000 IU hCG was given 50 hours later. Follicular fluid was aspirated from all visible follicles 36 hours after hCG. Women treated with hMG/hCG had multiple (two to five) follicles containing 1.5 to 4.5 ml of follicular fluid and a mature oocyte and elevated serum estrogen (400 to 800 pg/ml) on the day after hCG treatment. At the time of follicular fluid recovery, there was more inhibin activity (204 ± 14 U/10 ml) in the hMG/hCG-stimulated follicles than in unstimulated follicles of a control group of women (65 ± 14, mean ± standard error, P

The ovaries of 25 human infants from 18 to 200 days of age were obtained at autopsy, and their follicular fluid was subjected to measurement of inhibin activity, estrogen, progesterone, androstenedione, and testosterone. Significant inhibin activity was present in all samples of follicular fluid (charcoal-treated) (138 +/- 19 U/10 microliter follicular fluid; 10,545 +/- 2758 U/ovary). There was a tendency for greater inhibin activity, follicular volume, and estrogen in infants from 18 to 59 days than in older infants. There was a significant positive correlation between follicular fluid volume, estrogen, and androstenedione, compared with follicular fluid inhibin content per ovary. It is possible that elevated serum follicle-stimulating hormone and luteinizing hormone observed early in life stimulates follicle growth, inhibin, and estrogen production. As a result of elevated inhibin and estrogen, the gonadotropins may be inhibited, which may cause a decline in follicular activity after 4 to 6 months.

Ovarian tissue obtained from three human infants (60, 120, and 210 days of age) was separated into cell types and cultured. Granulosa cells from two of three subjects were viable and grew in culture. The cells had the potential to secrete low levels of progesterone and responded to luteinizing hormone and follicle-stimulating hormone added in culture with greatly enhanced ability to secrete progesterone. Granulosa cells could also secrete inhibin activity in culture and responded to luteinizing hormone and follicle-stimulating hormone with enhanced inhibin secretion. The granulosa cells also had the potential to secrete estrogen in the presence of testosterone. Serum levels of gonadotropin in the human infant are elevated for a period between 1 and 4 months; yet only follicular growth, not luteinization, occurs. It can be concluded that infant human granulosa cells, like adult human granulosa cells, have the potential of responding in vitro to gonadotropin.

Ovarian vein serum from 3 subjects during the late follicular phase of the menstrual cycle had detectable inhibin activity, whereas ovarian vein serum of 12 other subjects during the early follicular phase and luteal phase had no detectable inhibin activity in a rat anterior pituitary cell culture assay. Subjects having detectable inhibin activity (102 +/- 47 U/100 microliters) had 1257 +/- 582 U/100 microliters inhibin activity in FF, whereas subjects having no detectable inhibin activity had FF levels of 711 +/- 203 U/100 microliters of inhibin activity. Estrogen levels of FF and ovarian vein serum of the group having detectable inhibin activity in ovarian vein serum were 282 +/- 239 ng/ml and 4.8 +/- 1.77 ng/ml, respectively. The estrogen content of FF and ovarian vein blood of the group having nondetectable inhibin activity in ovarian vein blood was 127 +/0 45 ng/ml and 3.03 +/- 0.6 ng/ml, respectively.

Repetitious administration of charcoal-stripped porcine follicular fluid (pFF) to four intact cycling females and six long term castrate rhesus monkeys was associated with a gradual onset of resistence to the FSH-suppressing effects of pFF. After a treatment hiatus of 6 or more months, the pFFinduced selective suppression of FSH in circulation was again demonstrable, but only transiently; that is, within 10–14 weeks after the resumption of therapy, even large doses of pFF were no longer effective in reducing serum FSH in these monkeys. One monkey was studied through seven regimens over 4 yr. Accordingly, our series of investigations was divided into three parts. First, we observed that these changing FSH patterns were apparently due to cyclic fluctuations of pFF antibodies in conjunction with the intermittent schedule of pFF administration. The amnestic response to booster injections occurred within 7–14 days, followed by a gradual decline in the anti-pFF titer during succeeding months. Second, we tested ...

Publisher Summary This chapter discusses the role of nonsteroidal regulators in control of oocyte and follicular maturation. The ovarian follicle is bathed in a fluid rich in steroid hormones as well as nonsteroidal regulators which interact to serve to control its maturation, responsiveness to gonadotropins, as well as to lead to control of the maturation of its oocyte. The orderly maturation of an ovarian follicle and its oocyte is controlled by pituitary LH and FSH in concert with local intrafollicular regulators. The principal nonsteroidal follicular regulators are an oocyte maturation inhibitor, a luteinization inhibitor, a luteinization stimulator, FSH receptor binding inhibitor, and inhibin-F. OMI is a polypeptide

Inhibin activity, follicle-stimulating hormone (FSH)-suppressing substance, estrogen, progesterone, and androstenedione were measured in charcoal-treated ovarian tissue and ovarian venous and peripheral blood of eight rhesus monkeys ranging from 12 to 48 months of age. All of the monkeys demonstrated inhibin activity in ovarian tissue, which, if expressed per milligram protein, was relatively constant throughout development. However, if the activity was expressed per ovary, the amount of ovarian FSH-suppressing substance increased between 26 and 48 months; it was present in detectable amounts in ovarian venous blood only in one 26-month-old monkey. Detectable levels of estrogen were present in ovarian venous blood of the 26-month-old and the 48-month-old monkeys but not in the younger monkeys. It is possible that the secretion of inhibin activity may be in part responsible for low levels of serum FSH observed prior to puberty, because it has been observed by others that bilateral ovariectomy in the prepubertal monkey can result in a rise in FSH and that administration of charcoal-treated ovarian follicular fluid can suppress serum FSH in castrated prepubertal and adult rhesus monkeys.