The effects of ovulation-inhibiting steroids on plasma LH and FSH levels and the response to iv administration of LH-releasing hormone (LH-RH) were investigated in rats. Plasma LH levels were measured by ovarian ascorbic acid depletion (OAAD) assay and by radioimmunoassay (RIA). Plasma FSH was also measured by RIA. Subcutaneous administration of large doses of megestrol acetate, lynestrenol, Schering AG compound SH 1040 and Ayerst compound AY 11440 or of small daily doses for 5 days of combinations of megestrol acetate with ethinyl estradiol (Ovex) and lynestrenol with mestranol (Lyndiol), significantly depressed plasma LH levels in ovariectomized rats. The same compounds in large doses also depressed serum FSH levels, but small doses of Lyndiol and Ovex did not do so. Large doses of Lyndiol, Ovex, Schering AG compound SH 1040 and a combination of AY 11440 with ethinyl estradiol did not suppress the stimulatory effect of minute amounts (0.11–0.16 μ g) of LH-RH on LH release (3- to 10 fold increase). Similarly, sc administration of massive doses of 1 of the following 8 contraceptive preparations: Oracon, Ovral, Ortho-Novum, Enovid, Ovulen, Provest, Norlestrin or C Quens, depressed plasma LH to 1/5–1/3 of its basal concentration and also depressed plasma FSH. However, iv administration of 0.1 μ g LH-RH to these rats caused a 6- to 13-fold rise in plasma LH levels as determined by RIA. LH-RH was also active when given sc. Since the LH-RH preparation contained some FSH-releasing hormone (FSH-RH) activity, plasma FSH levels were also increased in groups treated with Oracon, Ortho-Novum, Provest and Enovid. This work again clearly demonstrates, in agreement with our previous studies, that contraceptive steroids do not block the stimulatory effect of LH-RH (and FSH-RH) and suggests that they act on the hypothalamus or on another brain center and not on the pituitary. The effects of oral administration of each of 10 steroidal contraceptive preparations on plasma LH were also studied in ovariectomized rats. When Oracon, Ovral, Ortho-Novum, Enovid. Ovulen, Provest, Norlestrin, C-Quens, Lyndiol or Ovex was given daily for 5 days by gavage in corn oil or carboxymethylcellulose aqueous vehicle, the amounts required for lowering plasma LH were 10 100 times those previously found effective by sc administration. Suppression of plasma FSH was also observed after oral administration of Ovex and Lyndiol.
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