Project: Research project

Project Details


Significant progress has been made during the last 5 years in elucidating
the complex mechanisms involved in the stimulatory and inhibitory effects
of progesterone on gonadotropin secretion. From these studies, a
multifactorial hypothesis explaining regulation of gonadotropin secretion
by progesterone has been proposed which includes progesterone regulation
of estrogen receptor dynamics, modulation of opioid tone, and modulation
of GABA and glutamate neurotransmission of the positive and negative
feedback effects of progesterone. This renewal application will further
elucidate mechanisms involved with the initiation and termination of the
gonadotropin surge and has 4 specific aims. SPECIFIC AIM 1 will
determine the mechanism of an increase in estrogen receptors of the
pituitary associated with the termination of the preovulatory
gonadotropin surge. The study will include measurement of pituitary ER
mRNA transcription and translation along with ER binding and degradation.
The role of a hypothalamic factor will also be investigated by using
hypothalamic-lesioned rats, a GnRH antagonist and NPY. SPECIFIC AIM 2
will determine the role of estrogens and progesterone on the regulation
of the opioid tone during the gonadotropin surge. The studies will
include the measurement of hypothalamic beta-endorphin, opioid receptors
and POMC mRNA levels and their correlation with gonadotropin secretion.
SPECIFIC AIM 3 will determine the role of GABA in progesterone-induced
inhibition and stimulation of gonadotropin secretion in the hypothalamus
and the pituitary. The study will use in vitro hypothalamic GnRH release
and pituitary FSH and LH release in the presence and absence of GABA
agonists and antagonists and intraventricular injection of GABA
antagonists. GABA receptors will also be measured. SPECIFIC AIM 4 will
determine the role of glutamic acid decarboxylase (GAD) in the
stimulation and suppression of gonadotropin secretion by progesterone.
The study will include measurement of hypothalamic GnRH, GABA, glutamic
acid, GAD activity and GAD mRNA levels during progesterone induced
stimulation and suppression of gonadotropin secretion. These studies
will provide new information on the neuroendocrine regulation of
gonadotropin secretion by progesterone.
Effective start/end date12/1/8111/30/99


  • Medicine(all)