The Effects of Anterior Hypothalamic Disconnection on Gonadotropin Secretion in the Female Rhesus Monkey*

Abstract

Studies to date have yielded contradictory data on the role of the anterior hypothalamus in the control of cyclic reproductive processes in the female rhesus monkey. In these experiments, we have studied the immediate and long term effects of anterior hypothalamic disconnection, using a transorbital approach, on spontaneous and estradiol-induced cyclic gonadotropin release. To secure an effective separation between the divided segments of the hypothalamus and to prevent the possibility of neural regeneration across the lesion, a Silastic membrane was introduced through the cut. Immunocytochemical studies, which selectively stained nerve fibers from the magnocellular nuclei, demonstrated no axonal growth through the cut. Eight adult female rhesus monkeys underwent hypothalamic disconnection; four were subsequently shown to have unilateral anterior lesions, and the remaining four had bilateral anterior cuts. All animals had PRL levels within the normal range (<12 ng/ml), except one (no. 577) whose bilateral lesion extended somewhat more caudally and who developed hyperprolactinemia [42.0 ±3.1 (SE) ng/ml], hyperphagia, and diabetes insipidus. The initial postoperative study (first 60 days after surgery) revealed that while all four of the unilaterally disconnected animals continued to show normal menstrual cyclicity, none of the four bilaterally lesioned monkeys released gonadotropins in response to spontaneously occurring estradiol surges or to 17β- estradiol challenges. However, in subsequent follow-up examination (4–7 months after surgery), bilaterally lesioned monkeys exhibited normal menstrual cyclicity and normal responses to estradiol challenge. These studies indicate that in the rhesus monkey, anterior hypothalamic afferents, originating either from the nuclei of this region and/or en passage from other neural structures, may act to modify the release of gonadotropins by the pituitary. However, long term observation of these animals as well as other evidence discussed in this paper clearly indicate that these modulatory influences are not essential for normal gonadotropin secretion.