The effect of clomiphene upon the FSH-RF content of the hypothalamus and plasma FSH-activity in ovariectomized, estrogen- progesterone blocked rats was examined. After the iv injection of 100–300 μg of clomiphene/ rat There was a significant decrease of hypothalamic FSH-RF content with a corresponding increase of plasma FSH-activity. The method described by Igarashi and McCann was used to measure FSH. An FSH-releasing effect of vasopressin which was contained in the hypothalamic extracts could be ruled out. It was concluded that clomiphene acts directly on hypothalamic receptor sites or interacts with estrogens at these sites, which results in a release of FSH-RF (Endocrinology84: 946, 1969)
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Baier et al. (1969) studied this question.