Beta-endorphin (Beta-EP) is capable of inhibiting the pituitary secretion of gonadotropin, but the mechanism(s) by which this opioid peptide controls the secretion of gonadotropin and affects reproduction is elusive at present. The main objective of this proposal is to study the neuroendocrine control of the secretion of hypothalamic Beta-EP in order to elucidate the mechanisms by which this opioid regulates gonadotropin release. The research will be done using a noval method for maintaining isolated rat hypothalamic neurons in primary culture, and by studying the in vivo secretion of hypothalamic hormones in pituitary portal blood of rats. Studies will be conducted to determine: 1) the secretory pattern of hypothalamic Beta-EP and LHRH (stimulates gonadotropin release) under two conditions in which the release of gonadotropin is known to be altered: the estrous cycle and hyperprolactinemia; b) the action of Beta-EP in the secretion of LHRH during the estrous cycle; c) whether Beta-EP plays any mediatory role in the positive and negative feedback actions of estradiol and progesterone on LHRH release; d) whether Beta-EP controls hyperprolactinemia-induced inhibition of LHRH secretion; e) the mechanisms of the action of steroids and prolactin on Beta-EP release; and f) the functional anatomy of the Beat-EP system. These studies will be carried out by elucidating the response of Beta-EP cells to various hormones in a primary hypothalamic neuron culture and by determining pituitary portal plasma concentrations of Beta-EP and LHRH under various experimental conditions. Attempts will be made to determine the dose-response relationship, time-course, and specificity of the action of the hormones. The site of the action of hormones will be determined by localizing the hormone bindings on the cells, and using cytochemical techniques. The functional anatomy of the Beta-EP system will be studied by comparing the effects of lesioning the mediobasal hypothalamus and other regions of CNS on Beta-EP release. The ability to now determine the interaction between Beta-EP and LHRH neurons in the hypothalamus should advance our knowledge of the neural control of reproduction, and yield basic information which may provide insight into the pathophysiology of hypothalmic ammenorrhea and reveal new approaches to contraception.
