# REGULATION OF OVARIAN STEROIDOGENESIS

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1994 · $180,318

## Abstract

The goals of this proposal are to understand the molecular basis for the
regulation of steroid hormone biosynthesis in the ovary, and in particular
for the unique episodic pattern of steroid hormone secretion that is
characteristic of the ovarian cycle.  This necessitates identifying the
elements in the genes encoding steroidogenic enzymes which are involved in
this regulation, as well as the factors which interact with these genomic
elements to mediate these actions.  It also necessitates examining
alterations in the structure of chromatin which may underlie changes in
the expression of specific genes, and the mechanisms responsible for such
changes.  Recent studies in this and other laboratories on the regulation
of expression of the genes encoding cholesterol side-chain cleavage
cytochrome P450 (CYP11A); 17alpha-hydroxylase cytochrome P45O (CYP17 and
aromatase cytochrome P450 (CYP19) have indicated that cyclic AMP
responsiveness of their expression is not directly mediated by the
classical CRE, namely TGACGTCA, nor its associated binding protein, CREB.
Rather, in the case of the bovine CYP11A gene, an Sp1-like element is
involved, whereas in the case of ovarian expression of the bovine CYP17
and the human CYP19 genes, the hexameric SF1/Ad4 binding element, AGGTCA,
is implicated. In the present Application, it is proposed to identify the
cell-signalling systems involved in the stimulation of expression of these
genes in the ovary by cAMP, as well as the mechanisms involved in
inhibition by TGF-beta, FGF, and phorbol esters. The roles of Sp1 and the
SF1/Ad4 binding protein in mediating cAMP responsiveness of their
respective signalling pathways will be determined by examining the action
of cAMP to phosphorylate these proteins in ovarian tissues, as well as the
role of cAMP in the regulation of the expression of these proteins and
their genes. The proteins with which these factors associate will be
defined on the basis of these interactions and the ability of the
associated proteins to be phosphorylated in response to cAMP will also be
characterized. The possible role of nuclear translocation of factors
involved in these signalling pathways in the response to cAMP will also be
defined. In this fashion, the signalling pathways involved in these unique
cAMP-mediated stimulatory mechanisms will be dissected. Similar studies
will be conducted to define the mechanisms whereby TGFbeta, FGF and
phorbol esters exert differential inhibition of expression of these genes.
We will also examine the cell-specific expression of these steroidogenic
genes in bovine and human ovary by determining the role of cis-acting
elements in such regulation, as well as changes in expression throughout
the cycle of the various transcription factors involved. Particular
emphasis will be placed on the role of changes in chromatin structure and
DNA methylation as mechanisms which regulate cell-specific expression, in
particular, the differential changes in expression of the CYP1...

## Key facts

- **NIH application ID:** 2196976
- **Project number:** 2R01HD013234-16
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** EVAN R SIMPSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $180,318
- **Award type:** 2
- **Project period:** 1979-07-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196976

## Citation

> US National Institutes of Health, RePORTER application 2196976, REGULATION OF OVARIAN STEROIDOGENESIS (2R01HD013234-16). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196976. Licensed CC0.

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