NEUROENDOCRINE CONTROL OF HYPOTHALAMIC B ENDORPHIN

Project Details

Description

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.
StatusFinished
Effective start/end date4/1/863/31/89

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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