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  • Author: L. A. Gribling-Hegge x
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A. I. Toorop and L. Gribling-Hegge

In the 5-day cyclic rat the ovarian androgen and oestrogen concentrations, measured by radioimmunoassay, started a gradual rise on the day of metoestrus, reaching maximal values in the period from 22.00 h on dioestrus 2 until 17.00 h on the day of pro-oestrus. A steep decline in the ovarian androgen and oestrogen concentrations occurred between 17.00 and 21.00 h on the day of pro-oestrus.

Rats, injected intraperitoneally with an ovulation-blocking dose of pentobarbitone sodium (35 mg/kg body weight) at 13.00 h on the day of pro-oestrus, tended to show a decline in ovarian concentrations of androgens and oestrogens during late pro-oestrus, but this decrease was less steep than in saline-injected rats. At 10.00 and 14.00 h on the day after pro-oestrus the ovarian concentrations of androgens and oestrogens in rats treated with pentobarbitone sodium showed a further decline but values were still higher than those in saline-treated oestrous rats. At 17.00 h, i.e. 28 h after injection with pentobarbitone sodium, a distinct increase in the ovarian androgen and oestrogen concentrations was noted and a steep decline was observed at 21.00 h on the day after pro-oestrus.

Thus normal as well as delayed ovulation was preceded first by an increase and then by a steep decline in ovarian concentrations of oestrogens and androgens.

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A possible role of 5α-androstane-3α,17β-diol (3α-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 3α-androstanediol alone was given as an ovarian substitute, an inhibitory effect on FSH release was evident with all three doses tested (50, 100, 300 μg/100 g body wt) between 13 and 30 days of age; at 33–35 days of age only the 300 μg dose caused some inhibition of FSH release. Results were more complex if 3α-androstanediol was given in combined treatment with oestradiol and progesterone. Given with progesterone, 3α-androstanediol showed a synergistic inhibitory action on FSH release between 20 and 30 days of age. However, when 3α-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 3α-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 3α-androstanediol might play a role in the control of FSH secretion in the immature rat, but after day 20 the potentially inhibitory action of 3α-androstanediol on FSH secretion is limited in the presence of oestradiol.

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The inhibitory action on FSH secretion of combined oestradiol and progesterone treatment of ovariectomized, immature rats was studied at various ages. At all ages studied (13–35 days) an additional inhibitory action of progesterone, if combined with oestradiol, could be found as compared with the effect of oestradiol alone. Until 20 days of age, the rise in serum FSH concentration as measured 2 days after ovariectomy could be completely prevented by administration of 0·05 μg oestradiol/100 g body weight or by administration of a lower dose of oestradiol (0·01–0·025 μg) combined with progesterone (0·5–1·5 mg/100 g body weight). After 20 days neither oestradiol nor the combined oestradiol/progesterone treatment resulted in an FSH concentration similar to that found in intact rats. However, the lowest FSH concentrations were reached by using combinations of oestradiol and progesterone.

Using progesterone alone, FSH concentration in ovariectomized rats was significantly reduced between 18 and 30 days of age, but not before or after this period.

Taken together with data on uterine weight and serum concentrations of progesterone, these findings suggest that (1) both oestradiol and progesterone exert an age-dependent role in regulating FSH secretion in the immature female rat, and (2) amounts of oestradiol and progesterone capable of maintaining, in ovariectomized rats, uterine weights not different from those in intact rats will maintain near-physiological concentrations of FSH before but not after day 20. Thus, ovarian factors other than oestradiol and progesterone must be involved in the regulation of FSH secretion in the female rat after 20 days of age.

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A. I. Toorop, L. Gribling-Hegge and H. M. A. Meijs-Roelofs

The present study examined the ovarian progesterone levels in rats during the normal 5-day oestrous cycle and in rats with an experimentally induced delayed or advanced ovulation. Ovarian androgen and oestrogen concentrations were also studied in rats with an advanced ovulation.

The ovarian progesterone concentrations during the normal cycle showed two peaks: one during metoestrus and dioestrus 1 and the second during the afternoon of pro-oestrus.

Rats treated with pentobarbitone sodium (35 mg/kg body weight) at 13.00 h on the day of pro-oestrus showed no increase in ovarian progesterone levels on that day, but did show an increase during the afternoon of the next day.

Rats injected intraperitoneally with an ovulation-inducing bolus of human chorionic gonadotrophin (hCG; 20 i.u.) at 15.00 h on the day before pro-oestrus (dioestrus 2) showed increased ovarian progesterone levels as early as 0·5 h after hCG injection. Lowered levels of ovarian androgen and oestrogen values compared with saline-injected rats were first found 2 and 6 h respectively after hCG injection.

In conjunction with data obtained previously these findings show that normal, delayed and advanced ovulations are preceded by an increase in ovarian progesterone concentrations and a subsequent decline in ovarian androgen and oestrogen levels.

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J. Th. J. Uilenbroek, H. M. A. Meijs-Roelofs, P. J. A. Woutersen, P. Kramer, W. A. van Cappellen, L. A. Gribling-Hegge and W. J. de Greef


To determine whether the decrease in ovarian 5α-reduced androgen production before first ovulation might be caused by an increase in serum LH, prepuberal female rats were injected at 28–31 days of age with low doses of human chorionic gonadotrophin (hCG) (0·05–0·075 i.u., four times daily). This treatment resulted in ovulation of six to ten ova per rat on day 32 in all animals.

Treatment with hCG resulted in a gradual decrease in ovarian content and production (i.e. content in ovary and medium after 4 h of incubation) of 5α-dihydrotestosterone (DHT) and 5α-androstane-3α,17β-diol. The ovarian content of DHT and the production of 5α-androstane-3α,17β-diol decreased within 24 h after the first injection of hCG. Oestradiol content and production increased between 24 and 48 h after the start of treatment and was maximal on day 31 (day of pro-oestrus).

Activities of 5α-reductase and aromatase were measured in ovarian homogenates obtained on days 29–31. Activity of 5α-reductase in hCG-treated rats was lower than that in control rats on all days studied. Aromatase activity in hCG-treated rats increased between days 29 and 31.

It was concluded that multiple injections of low doses of hCG, which may induce ovulation, cause a decrease in 5α-reduced androgen production, which is probably due to a decrease in 5α-reductase activity. The subsequent increase in oestradiol production corresponds with an increase in aromatase activity. The results indicate that the decrease in 5α-reductase activity as observed in ovaries of spontaneously ovulating rats might be caused by the gradual increase in serum LH, which has been found to occur during the last week before first ovulation.

J. Endocr. (1985) 107, 113–119