The interaction of GnRH with its receptor is undoubtedly the initial stimulus for inducing release of LH and FSH from the gonadotroph; however, the mechanisms responsible for regulating the number of receptors, and the importance of increasing or decreasing the number of receptors for controlling secretion of gonadotropins is largely unknown. The proposed research is designed to relate changes in the number of receptors available for binding GnRH with the ability of the anterior pituitary gland to release LH. These studies will correlate changes in the number of receptors for GnRH in the anterior pituitary during the periovulatory period with the dramatic differences in gonadotropin secretion that occur at this time. We will also utilize """"""""down-regulation"""""""", and treatment with an inhibitory analog as other methods for manipulating the number of receptors available to stimulate release of LH and FSH. Using these approaches we anticipate that it will be possible to determine the number of receptors that must be saturated with hormone to effect release of LH, and to determine how many receptors must be saturated with hormone to effect release of LH, and to determine how many receptors must be removed (either by """"""""down-regulation"""""""" or masked with inhibitory analog) to prevent LH release in response to a physiological stimulus. We also propose to examine the cellular mechanism involved in internalization of GnRH receptors. We hope to provide information concerning the following questions: 1) must receptors be occupied to be internalized? 2) Must adenylate cyclase (a membrane bound enzyme) be stimulated for internalization of receptors to occur? and 3) will stimulation of intracellular processes induce internalization of receptors? Finally, we propose to examine the relationship between the concentration of LH in the pituitary gland and the magnitude and frequency of pulses of LH in the circulation. We have chosen the ewe as a model for the proposed studies due to the extensive background information available, the ability to collect frequent blood samples for extended periods of time, the large quantity of adenyohypophy seal tissue available (approximately g/sheep) and the similarities of the mechanisms regulating reproductive function between ewes and women. We anticipate that the proposed research will provide new, basic information that will be useful for developing more afficient and safer methods for regulating fertility in humans, meat - and milk-producing species and companion animals.
