Project: Research project

Project Details


This project addresses the fundamental issue of whether excitatory amino
acids (EAAs), such as glutamic acid or aspartic acid, are involved in
the neuroendocrine regulation of gonadotropin secretion in the female
rat. While significant work has been done in the male on this question,
surprisingly little work has been performed in the female. Gaining a
better understanding of the neuroendocrine events and mechanisms which
regulate the gonadotropin surge in the female is important, since it
could lead to new ways to regulate reproduction and to new methods for
treating infertility.

The proposed study will determine the ability of EAAs to regulate GnRH,
gonadotropin and prolactin secretion in the female rat using both in
vitro and in vivo approaches. In vitro studies will examine the ability
of a variety of natural (endogenous) and synthetic EAAs to regulate GnRH
release from hypothalami of estrogen-primed ovariectomized (ovx.) adult
rats perfused in vitro. The specific receptor mediating each EAA effect
will also be determined as will the ability of each EAA to repetitively
stimulate GnRH release. EAAs will also be administered in vivo to
validate that the effects observed in vitro are real effects that can be
observed in the natural in vivo environment. Aim 2 will examine whether
EAA effect is influenced by gonadal steroid background. Ovx. rats with
and without estradiol or estradiol plus progesterone replacement will be
used in this aim. Both in vitro GnRH release and in vivo LH, FSH and
PRL release after EAA administration will be assessed in these animals.

In Aim 3, specific NMDA and non-NMDA receptor antagonists will be
employed in ovx. estrogen-progesterone treated animals, and during the
different days of the cycle to determine the physiological role of EAAs
in negative and positive feedback regulation. Furthermore, the role of
endogenous EAAs in pulsatile GnRH and LH release in the female will also
be examined. Aim 4 will determine if the effect of EAAs on GnRH, LH,
FSH and prolactin release is mediated through effects on other
neurotransmitter systems (catecholamine, acetylcholine and NPY) known to
regulate the release of these hormones and releasing hormones. Specific
antagonists to each respective system mentioned above will be utilized
in vitro and in vivo to answer this question. Also, the possibility
that these neurotransmitter systems could use EAAs to mediate their
effect on GnRH, gonadotropin or PRL release will be examined. Aim 5
will examine whether steroids can modulate EAA receptor density and
affinity in neuroendocrine tissues such as the hypothalamus using ovx.
rats with and without steroid replacement, as well as cycling rats on
each day of the cycle. These studies will provide important new
information on the precise role of EAAs in the regulation GnRH,
gonadotropin and prolactin secretion in the female.
Effective start/end date4/1/923/31/07


  • Medicine(all)