# PITUITARY GONADOTROPIN GENE REGULATION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1994 · $196,067

## Abstract

The anterior pituitary plays a central role in the regulation of
reproductive function, growth, lactation, stress response, and endocrine
homeostasis.  The pituitary also serves as an excellent model in which to
study the complex molecular interactions involved in development and
organogenesis in mammalian systems.  The anterior lobe rises from the
somatic ectoderm by formation of Rathke's pouch.  Within this primitive
organ five distinct endocrine cell types arise.  These are, in
developmental order of appearance:  corticotropes which produce pro-
opiomelanocortin, thyrotropes which produce thyrotropin-releasing hormone
(TSH), gonadotropes which produce both luteinizing hormone (LH) and
follicle-stimulating hormone (FSH), somatotropes which produce growth
hormone, and lactotropes which produce prolactin.  Substantial information
is available concerning the molecular events important for regulation of
growth hormone and prolactin gene expression;  however, much less is known
about the determination of  pituitary gene expression of the family of
glycoprotein hormones, LH, FSH,and TSH.  These hormones are heterodimeric
proteins composed of a common a subunit and distinct beta subunits encoded
by individual gene.  The temporal appearance of the individual subunits is
not coordinated and indicated that the alpha-subunit gene may be expressed
in a common early progenitor cell for all endocrine lineages of the
anterior pituitary.  Thus, development of the individual cell types may
involve independent activation of specific hormone genes coupled with
specific restriction of gene expression.

The molecular basis of regulation of the LH  and FSH genes in gonadotropes
could not be effectively investigated heretofore due to lack of appropriate
cell lines.  Tumors derived by pituitary-specific expression of the SV40 T-
antigen oncogene in transgenic mice have allowed us to isolate clonal cell
lines representing cells in the developmental lineage of the gonadotrope
which express either  the common alpha-subunit or both the alpha and  LH
beta-subunit genes.  In this proposal, we investigate three major  issues:
A.  The mechanisms of developmental and tissue-specific control of the
gonadotropin genes in pituitary cells, including the roles of both
transcriptional activation and restriction in directing unique patterns of
gene expression.  B.  The molecular basis of hormonal regulation of
gonadotropin gene expression, with emphasis on induction of gene expression
by hypothalamic gonadotropin-releasing hormone and repression by gonadal
steroids.  C. The molecular events determining the developmental lineage of
the gonadotrope in the anterior pituitary, utilizing approaches transgenic
mice including targeted immortalization, cell ablation, and ectopic
expression of regulatory proteins.  These investigations will lead to
detailed understanding of the molecular events governing the developmental
and hormonal regulation of the gonadotrope and pituitary development.

## Key facts

- **NIH application ID:** 2198005
- **Project number:** 5R01HD020377-11
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** PAMELA L MELLON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $196,067
- **Award type:** 5
- **Project period:** 1992-01-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198005

## Citation

> US National Institutes of Health, RePORTER application 2198005, PITUITARY GONADOTROPIN GENE REGULATION (5R01HD020377-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198005. Licensed CC0.

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