Oestradiol-17\g=b\(E2) was measured by radioimmunoassay in the plasma of immature female rats. Maximal E2 levels of 55\p=n-\60 pg/ml were found at 10\p=n-\15 days of age; from day 25 to day 35 E2 levels were low to undetectable. The E2 measured appeared to be of ovarian origin: ovariectomy performed on day 13 resulted in a decreased E2 level 2 days later (13 pg/ml) as compared with the value from the control litter mates (46 pg/ml); after adrenalectomy the level of circulating E2 remained normal (54 pg/ml). The effects of ovariectomy and adrenalectomy on uterine weights followed a similar pattern: ovariectomy resulted in a decrease and adrenalectomy in no change in uterine weight.In the strain of rat used, levels of follicle-stimulating hormone (FSH) in the serum (measured by radioimmunoassay) were high from day 10 to day 20 and showed a steep decrease on day 21. After ovariectomy on day 15 this decrease in serum FSH was not observed.The influence of circulating E2 on serum levels of FSH was studied after ovariectomy followed by treatment with varying doses of oestradiol benzoate. Ovariectomy on day 13 resulted in a significantly increased FSH level 2 days later (1770 ng NIAMD-rat-FSH RP-1/ml) as compared with the value obtained from control animals (1033 ng/ml). This increase was not observed after daily injections of 0\ m=. \ 1\g=m\g oestradiol benzoate/100 g body weight.The results indicate that E2 and FSH concentrations show a similar pattern between 5 and 35 days of age. Furthermore, an inhibitory feedback mechanism between oestrogens and FSH concentrations was found to be operative. The implications of these findings are discussed.

The maturation of the inhibitory feedback action of oestrogen on FSH secretion in the immature female rat was studied from 5 days of age until after the first ovulation. To study the role of the oestrogen binding alpha-foetoprotein (AFP) which is present in the blood of young animals, the effects of various doses of oestradiol and of the synthetic oestrogen R2858 (11 beta-methoxy-17-ethynyl-oestradiol), which is not bound by AFP, were compared in ovariectomized rats. A rise in the serum concentration of FSH within 2 days of ovariectomy was first observed in rats ovariectomized at 8 days of age. Between 8 and 28 days of age the rise in FSH after ovariectomy could be prevented by oestrogen injections in such a way that the resulting FSH concentration amounted to 50% of that in ovariectomized control rats. This was achieved with a constant dose of 0.00015 microgram R2858/100 g body weight, whereas the dose of oestradiol needed decreased from 0.05 to 0.01 microgram/100 g body weight indicating an increased sensitivity to the feedback action of oestradiol. After day 28, sensitivity to the feedback action of both R2858 and oestradiol decreased progressively up to the time of the first ovulation. In contrast to results at earlier ages, none of the doses of either oestrogen was capable of maintaining near-physiological concentrations of FSH after 20 days of age. It is concluded that the apparent increase in sensitivity to the feedback action of oestradiol occurring before 28 days of age reflects the disappearance of AFP from the blood, whereas the subsequent decrease in sensitivity is independent of AFP. Moreover, it is concluded that up to about 20 days of age oestradiol could be, though not necessarily is, the sole ovarian factor involved in regulating FSH secretion, whereas at later ages additional steroids and/or factors must be involved.

Luteinizing hormone, FSH, prolactin, oestradiol and progesterone concentrations were measured by radioimmunoassay in the blood of female rats from 7 days before the first ovulation (the day of first ovulation is designated day 0) until the day after the second ovulation. Serum LH concentrations varied between 29 and 59 ng NIAMDD-rat-LH RP-1/ml from days -7 to -2. On the day preceding first ovulation (day -1) a steep increase in serum LH was found between 13.00 h and 15.00 h reaching a maximal value of 2100 ng/ml at 17.00 h. Thereafter LH levels decreased to undetectable values (less than 15 ng/ml). Serum FSH concentrations from days -7 to -2 varied between 108-154 ng NIAMDD-rat-FSH RP-1/ml; increased concentrations were found on the afternoon of day -1 and on the morning thereafter (first oestrus) with a maximal value of 1150 ng/ml at 19.00 h on day -1. On the day preceding the second ovulation (day +4) LH and FSH peaks were again found. Prolactin concentrations on the days preceding first ovulation were generally low. A small rise was found nearing first ovulation (12-7 ng/ml, day -6; 23-9 ng/ml, day -2). On day -1 a peak (118 ng/ml) was found at 15.00 h, similar to that found on day +4 in adult pro-oestrous rats. Plasma progesterone concentrations also reached a peak value (50 ng/ml) on day -1, at 17.00 h, preceded by concentrations between 3-5 ng/ml from days -6 to -2. Progesterone concentrations after the first ovulation showed a pattern characteristic of the adult cycle. Plasma oestradiol levels were un-etectable (less than 10 pg/ml) from days -6 to -2; a clearly increased oestradiol concentration was found on day -1, reaching a value of 98 pg/ml. One and two days before the second ovulation, oestradiol levels rose again. The differences and similarities between pubertal and adult pro-oestrous hormone peaks are discussed.

Ovarian follicular development was studied in the rat during a 15-day period preceding first ovulation. Ovaries were obtained by unilateral ovariectomy performed at various ages and the rats were allowed to live until the day after first ovulation. The timing of this ovulation was compared with that in unoperated, paired control rats of the same age. For estimation of gonadotrophin levels, blood was taken from the paired control rats at the time when experimental rats were unilaterally ovariectomized. There was no evidence that unilateral ovariectomy had any influence on the timing of first ovulation. Therefore the ovaries obtained could be dated in relation to first ovulation, and follicular growth during the final prepubertal period could thus be studied in a genuine developmental sequence. Results revealed that follicular growth leading to first ovulation starts at +/- 8 days before this ovulation; follicular processes taking place are comparable to those found during the adult 5-day cycle but proceed more slowly. Gonadotrophin concentrations accompanying the follicular dynamics and measured at 11.00 h, showed a clear tendency for FSH concentrations to decrease with increasing age, i.e. approaching first ovulation. Concentrations of LH did not show a definite pattern and were generally low, although in some individual rats relatively high LH values ( greater than 100 micrograms/l) were found in the period of 5-3 days before first ovulation.

Concentrations of LH in the serum were estimated in rats bled either once or twice during a 15-day period preceding first ovulation. In rats bled once (between 09.00 and 17.00 h) serum concentrations showed little change between 15 and 9 days before first ovulation and averaged 16 micrograms/l (days -15 to -9). A shift in LH level, to a mean of 31 micrograms/l, was seen on day -8, whereafter LH concentrations increased gradually. Basal LH values of less than 10 micrograms/l were only found until day -4. The finding that LH values increased with age was confirmed by data from rats bled twice with an interval of greater than or equal to 3 days between bleedings. Furthermore, both in rats bled twice at 11.00 h and in rats bled twice at 15.00 h LH concentrations were significantly higher in the second sample. Both morning (11.00 h) and afternoon (15.00 h) LH concentrations in rats bled once also indicated a rise in LH concentrations with age but it became apparent that only morning values showed a shift in LH concentration (from approximately 15 to approximately 42 micrograms/l) from day -9 to day -8. In contrast, mean afternoon values showed a gradual increase from day -15 on. From day -8 on the number of rats with LH values greater than or equal to 50 micrograms/l increased, and from day -5 on they were more frequent at 15.00 than at 11.00 h. Thus a clear increase in LH secretion, most likely of a pulsatile nature, was found in the female rat approaching puberty. The correlation in time and possible functional relationship with late-prepubertal follicular growth is discussed.