# GONADOTROPIN-RELEASING HORMONE ACTION

> **NIH NIH R37** · UNIVERSITY OF IOWA · 1994 · $294,479

## Abstract

Studies dealing with the biochemical and molecular mechanism of
gonadotropin releasing hormone (GnRH) action have served to: (a) identify
new clinical and veterinary uses for GnRH and its analogs, (b) bring these
uses to fruition through a rational process based on understanding of the
mechanism of hormone action, and (c) provide the means for anticipating,
understanding, and ameliorating side-effects of the agents. FDA approvals
of GnRH agonists for the treatment of prostate cancer, endometriosis, and
precocious puberty, as well as for the use of natural sequence GnRH to
induce ovulation, and to test the hypothalamic-pituitary-gonadal axis, are
examples of the clinical usefulness derived from these fundamental
observations.  There are multiple advantages to the study of GnRH-
stimulation of the gonadotrope that make it facile to collect
interpretable data: (a) GnRH stimulation of the gonadotrope cell has
clearly defined, specific and measurable endpoints: release of endocrine
(and potentially endocrine) substances (LH, FSH, secretogranin II, alpha-
subunit of gonadotropin), regulation of target cell sensitivity,
regulation of the GnRH receptor, and biosynthesis of released substances.
(b)The releasing hormone itself (as well as its agonists and antagonists)
can be radioiodinated to high specific activity.  (c) Many (>3,000)
analogs exist that can be chemically derivatized without loss of
biological activity.  Antagonists and agonists which bind the receptor
with greater affinities than the natural sequence GnRH are available.  (d)
Virtually all known agonists and antagonists are "pure" in action and
metabolically stable agonists are available.  The present project is
divided into three areas of focus that are detailed in the "Specific Aims"
section and form the basis of organization of the "Research Design and
Methods" section. The first area will provide information on the structure
of the GnRH receptor and early actions following the interaction of the
receptor with GnRH and its analogs.  At the present time, due to technical
difficulties in dealing with the receptor itself, it has not been possible
to use standard techniques to purify or even solubilize the receptor for
a protracted period.  Accordingly, these studies should advance our
understanding of the receptor in the mechanism of GnRH action.  The second
area will provide information on the relationship between the multiple
effector mechanisms already implicated in GnRH action with the multiple
actions stimulated by the releasing hormone (release of multiple endocrine
substances, regulation of target cell responsiveness, biosynthesis, and
regulation of receptor number). This is important since considerable
confusion remains regarding these relationships.  The third area involves
understanding the molecular sites of action of activin and inhibin in
relation to GnRH action and are significant to understand the actions of
these agent in vivo.

## Key facts

- **NIH application ID:** 2197886
- **Project number:** 2R37HD019899-10A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **SAM.gov UEI:** Z1H9VJS8NG16
- **Principal Investigator:** P. MICHAEL CONN
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $294,479
- **Award type:** 2
- **Project period:** 1984-04-01 → 1998-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197886

## Citation

> US National Institutes of Health, RePORTER application 2197886, GONADOTROPIN-RELEASING HORMONE ACTION (2R37HD019899-10A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197886. Licensed CC0.

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