Gondatropin-releasing hormone (GnRH) is probably secreted from hypothalamic neurons in distinct, periodic pulses. These rhythmic bursts of GnRH then initiate the secretion patterns of gonadotropins. The frequency and amplitude of these neural and pituitary events are influenced, in turn, by the changing ciruclating levels of two ovarian steroids, estradiol and progesterone. Still to be clarified are the specific cellular events in this process, the identity of the other humoral agents (prolactin, monoamines, or opiates) that may alter these events, and their mechanisms of action. The identity of prolactin-releasing factor (PRF), its mode of secretion, and the neurochemical eents and neuroanatomical regions that regulate prolactin secretion must also be studied. With specific radioimmunoassays for gonadotropins, steroids, prolactin, and GnRH, two types of infusion-withdrawal devices, and an assay to measure 125I-labeled GnRH on pituitary cell membranes, we propose to determine GnRH secretion and GnRH receptor binding characteristics; to correlate these variables with gonadotroping secretion; and to determine the sites of estrogen and progesterone action in macaques. To explore the hypothesis that neural peptides other than GnRH are also secreted rhythmically, we will study the neurochemical events and neuroanatomical regions that control the synchronous release of luteinizng hormone (LH) and prolactin. Neural deafferentation, local lesioning, electrical stimulation, pituitary stalk transection, hypophysectomy, and hypophyseal transplantation will be used in conjunction with hormone and drug therapy. Finally, we wish to examine the release of prolactin with hormone and drug therapy. Finally, we wish to examine the release of prolactin and LH in a physiologic state in which prolactin release occurs and LH release may not. Thus, we will monitor prolactin and LH changes in serum during infant suckling and compare them with the changes after hypophyseal stalk transection and after pituitary transplantation. The studies will provide the first direct evidence of the events that control GnRH secretion in awake primates and will enhance our understanding of the neural and hormonal events controlling gonadotropin and prolactin secretion. This knowledge may help identify the causes of hyperprolactinemia and hypogonadotropism and their potential interactions in reduced fertility.
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