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Hypothalamic Sites of Action for Methallibure (ICI 33828) Inhibition of Gonadotropin Secretion

Purdue University, Lafayette, Indiana 47907

Abstract

Small quantities of the compound methallibure (ICI 33828) were surgically implanted in the anterior pituitary or hypothalamus of female guinea pigs on day 12 of the estrous cycle. Eight days later the ovaries were examined for the presence of new CL and the exact location of each methallibure implant was determined. Relatively large implants of methallibure within or near the hypothalamus prevented ovulation in 13 of 14 cases while similar implants within the anterior pituitary prevented ovulation in only two of eight animals. Relatively small implants of methallibure within or near the hypothalamus blocked ovulation in 26 of 47 cases while ovulation occurred in all of 21 animals with control implants. Ovulation could be blocked for the 8 day experimental period with as little as 20 µg methallibure. Those animals in which ovulation was blocked had methallibure implants in many different sites. The most consistent inhibition of ovulation occurred when methallibure was implanted in the arcuate nucleus-median eminence region or in the pre-optic area. Ovulation was also blocked in a less consistent manner by implants located in the dorsomedial hypothalamus or in the lateral hypothalamus and the ventral part of the medial forebrain bundle. Methallibure implants which blocked ovulation were never able to prevent growth, preovulatory luteinization and persistent estrogen secretion by the ovarian follicles. Similarly, intrahypothalamic methallibure did not consistently reduce feed consumption beyond that caused by the surgical procedures of intracranial implantation.

¹ Paper No. 4159, Purdue University Agricultural Experiment Station. A contribution from the Department of Animal Sciences. Supported in part by a grant from Ayerst Laboratories and in part by U. S. Public Health Service grants HD 02423 and HD 23284.