A synergistic effect of 20∞OH pregn-en-3-one (20∞P) on estrogen induced LHFSH peak was demonstrated in castrate female rats. When high doses of 40 μg and 100 μg/day ethinyl estradiol (EE) were administered over 5 days time to castrate rats, a biphasic response in serum LH was seen. During the first 4 days, LH concentrations progressively fell and then on day 5 a surge or peak occurred. FSH also fell progressively, but no peak occurred on day 5. Lower doses of EE resulted in suppression of both serum LH and FSH, but no surge of LH occurred. However, when 20∞P was added on the Sth day of treatment with a subthreshold (for stimulation of LH) dose of EE (0.4 μg/day), a surge in both serum LH and FSH occurred. If progesterone was given instead of 20∞P on day 5, a surge of serum LH but not FSH occurred. 17∞OH progesterone (17∞P) had no synergistic effect. P, 20∞P or 17∞P given alone to castrate rats had no effect on serum LH or FSH. We postulate that in rats 20∞P may have a synergistic effect with estradiol in the induction of the proestrous LH-FSH surge. (Endocrinology90: 1529, 1972)
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Swerdloff et al. (1972) studied this question.