Clomiphene citrate induces luteinizing hormone release through hypothalamic luteinizing hormone-releasing hormone in vitro

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Abstract
The releasing effects of clomiphene citrate (clomiphene) on luteinizing hormone (LH) and hormone LHRH were examined in a sequential double chamber superfusion system by superfusing the mediobasal hypothalami (MBH) and/or pituitaries excised from normal female rats in diestrus. When the MBH and the pituitary were superfused in sequence with medium containing 2 .times. 10-10 M estradiol (E2), 2 significant peaks in LH release (60-130% increase, P < 0.05) were observed 40 min and 90 min after the administration of 3 .times. 10-8 M clomiphene. Administration of clomiphene in medium without E2 induced a low peak (25-50% increase, P < 0.05) of LH released from the pituitary perfused in series with the MBH. Administration of clomiphene did not cause a marked increase of LH from the pituitary superfused alone, when superfused with or without E2 containing medium. The concentration of LHRH in the efflux was significantly increased (50-100%) 40 min and 90 min after clomiphene administration when MBH was superfused with medium containing E2, while clomiphene had no effect when superfused with medium alone. Clomiphene induces LHRH release from the MBH; it may induce LH release, in part, by acting directly at the pituitary level; changes in LH after clomiphene administration coincide with LHRH release, and a certain concentration of E2 may be necessary for the secretion of LHRH by clomiphene.