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.

No abstract

The presence and physiological significance of ovarian inhibin-like activity (ILA) in immature rats was studied by measuring ILA in ovarian homogenates and by studying the short-term changes in serum concentrations of FSH and LH after unilateral or bilateral ovariectomy. Inhibin-like activity in ovarian homogenates was estimated using an in-vitro bioassay system with dispersed rat anterior pituitary cells and subsequent measurement of FSH and LH levels in the spent pituitary cell medium. Inhibin-like activity, expressed in units/ovary, was undetectable in 13-day-old ovaries, was present in 18-day-old ovaries (5.8 units/ovary) and rose significantly to a value of 29.1 units/ovary on day 23. Another significant rise was seen between 28 and 33 days of age, with ILA reaching a value of 66.4 units/ovary, a value still well below that found in adult dioestrous ovaries (155.6 units/ovary). In the bioassay no systematic dose-dependent influence on LH secretion was found. Serum concentrations of FSH after unilateral or bilateral ovariectomy at 18 days of age showed no change at 5h and a significant (P less than 0.05) increase compared with sham-operated controls at 24 h after operation. At 23, 28 and 33 days of age significant increases in FSH concentration were seen at 5 and 8 h after both unilateral and bilateral ovariectomy. At 24 h after unilateral ovariectomy, FSH had returned to the control values in these rats, whereas after bilateral ovariectomy a further increase in FSH was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Antiprogestins form a new potential treatment modality for breast cancer and their mode of action has been assessed in vitro on several breast cancer cell lines, in vivo in rats with dimethylbenzanthracene (DMBA)-induced mammary tumours and in vivo in patients with metastatic breast cancer. In vitro in serum-free medium, the progestin Org 2058 and antiprogestins RU486 and Org 31710 caused a dose-dependently stimulated MCF7 cell growth. Both antiprogestins dose-dependently inhibited the oestrogen-stimulated proliferation of progesterone receptor (PgR)-rich T-47D cells in DCC medium. Inhibition by Org 31710 plateaued at 10(-8) M (74% inhibition), compared with RU486 at up to 10(-6) M (53% inhibition). No inhibition was observed at doses of 10(-12)-10(-6) M of both antiprogestins in the absence of oestradiol. The proliferation of the ZR-75.1 and MDA-MB-231 cell lines was not or only marginally affected by either antiprogestin. Rats with DMBA-induced mammary tumours given prophylactic treatment with RU486 displayed a doubled latency period. Antiprogestins were slightly more effective than tamoxifen or progestins in rats with existing tumours. Org 31710 sometimes showed a somewhat more pronounced inhibitory effect than the antiprogestins Org 31806 and RU486. Combined antiprogestational and anti-oestrogenic treatment showed striking additive growth inhibitory effects resulting in clear tumour remissions, in the presence of very strong suppression of oestrogen and PgRs. The growth inhibitory effect of luteinizing hormone-releasing hormone agonists was potentiated by antiprogestins.(ABSTRACT TRUNCATED AT 250 WORDS)