A possible role of clomiphene citrate in the control of pre-ovulatory LH surge during induction of ovulation

Abstract

A possible role of clomiphene citrate (clomiphene) in the control of ovulation in anovulatory women was investigated. Since a single i.p. administration of 5 .mu.g estradiol-17.beta. (E2) to long-term ovariectomized rats did not induce LH [luteinizing hormone] surge, the following studies were designed to determine whether pretreatment with clomiphene followed by administration of E2 could induce LH surge in the ovariectomized rats. Changes in cytoplasmic and nuclear estrogen receptors (ER) were also examined in the pituitaries of these animals. An i.p. injection of 200 .mu.g clomiphene suppressed serum LH levels significantly for 72 h. The clomiphene injection rapidly caused an elevation of nuclear ER with a concomitant depletion of cytoplasmic ER level in the pituitary and the ER levels reamined almost unchanged for 72 h. An administration of E2 12 or 24 h after the clomiphene injection had no significant effects on either the serum LH levels or the cytoplasmic and nuclear ER levels, compared with those induced by clomiphene alone. LH surge and the depletion of nuclear ER in the pituitary occurred 24 h later when E2 was injected 48 h after the clomiphene administration. The E2-induced LH release seems to be induced by a replacement of clomiphene by E2 on the nuclear receptor complex. Clomiphene may exert actions directly on the pituitary gland to augment estrogen-induced LH release.