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

Abstract

The releasing effects of clomiphene citrate (clomiphene) on luteinizing hormone (LH) and LH-releasing hormone (LRH) were examined in a sequential double chamber superfusion system by superfusing the mediobasal hypothalami (MBH) and/or pituitaries excised from normal female rats in dioestrus. When the MBH and the pituitary were superfused in sequence with medium containing 2 X 10(-10) M oestradiol (E2), two significant peaks in LH release (60-130% increase, P less than 0.05) were observed 40 min and 90 min after the administration of 3 X 10(-8) mol clomiphene. Administration of clomiphene in medium without E2 induced a low peak (25-50% increase, P less than 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 LRH in the efflux was significantly increased (50-100%) 40 min and 90 min after clomiphene administration when MBH was superfused with medium containing E2, whereas clomiphene had no effect when superfused with medium alone. These data indicate: 1) that clomiphene induces LRH release from the MBH, that it may induce LH release, in part, by acting directly at the pituitary level; 2) that changes in LH after clomiphene administration coincide with LRH release, and 3) that a certain concentration of E2 may be necessary for the secretion of LRH by clomiphene.