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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD020498-02
Application #
3318644
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Sarkar, D K; Minami, S (1995) Diurnal variation in luteinizing hormone-releasing hormone and beta-endorphin release in pituitary portal plasma during the rat estrous cycle. Biol Reprod 53:38-45
Sarkar, D K; Mitsugi, N (1990) Correlative changes of the gonadotropin-releasing hormone and gonadotropin-releasing-hormone-associated peptide immunoreactivities in the pituitary portal plasma in female rats. Neuroendocrinology 52:15-21
Sarkar, D K; Sakaguchi, D S (1990) Characterization of the neurosecretory activity of hypothalamic beta-endorphin-containing neurons in primary culture. Endocrinology 126:349-56
Minami, S; Frautschy, S A; Plotsky, P M et al. (1990) Facilitatory role of neuropeptide Y on the onset of puberty: effect of immunoneutralization of neuropeptide Y on the release of luteinizing hormone and luteinizing-hormone-releasing hormone. Neuroendocrinology 52:112-5
Sarkar, D K; Friedman, S J; Yen, S S et al. (1989) Chronic inhibition of hypothalamic-pituitary-ovarian axis and body weight gain by brain-directed delivery of estradiol-17 beta in female rats. Neuroendocrinology 50:204-10
Sarkar, D K (1989) Evidence for prolactin feedback actions on hypothalamic oxytocin, vasoactive intestinal peptide and dopamine secretion. Neuroendocrinology 49:520-4
Sutton, S W; Mitsugi, N; Plotsky, P M et al. (1988) Neuropeptide Y (NPY): a possible role in the initiation of puberty. Endocrinology 123:2152-4
Sarkar, D K (1987) In vivo secretion of LHRH in ovariectomized rats is regulated by a possible autofeedback mechanism. Neuroendocrinology 45:510-3
Lira, S A; Phipps Jr, D W; Sarkar, D K (1986) Loss of estradiol-positive feedback action on LH release during prepubertal period in rats treated postnatally with an opiate antagonist. Neuroendocrinology 44:331-7