# HORMONAL REGULATION OF GENE EXPRESSION IN SERTOLI CELLS

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1994 · $228,967

## Abstract

FSH and androgens act on Sertoli cells to regulate the secretion of
proteins that function in the control of spermatogenesis, however, the
mechanisms by which these hormones regulate Sertoli gene expression is not
known.  The expression of one of the major secretory proteins, androgen-
binding protein (ABP), parallels the regulation of spermatogenesis.  During
the two years of funding we have developed the rat ABP gene as a model
system to study the molecular mechanisms of hormone-mediated gene
regulation of the Sertoli cell.  Our accomplishments include isolation and
characterization of testicular ABP cDNA and the ABP gene.  Furthermore, as
a collaborative effort we have cloned and characterized the rat androgen
receptor (AR) cDNA and generated specific antibodies to AR.  With ABP cDNA
as probe we have begun elucidation of the mechanisms of ABP hormonal
regulation.

With the developed tools described above, we propose to extend these
studies with three specific aims:  1.  Locate ABP gene regulatory elements,
including promoters, Sertoli cell specific enhancer elements and hormone
regulatory elements, utilizing in vitro transfection of CAT vector
constructs on primary Sertoli cells and transgenic animals.  2.  Delineate
the effects of FSH and androgen on ABP gene expression.  In vitro studies
with Sertoli cell cultures will be used to determine if these hormones have
direct or indirect effects on ABP gene expression.  We will also determine
modulatory effects of other hormones, paracrine and autocrine factors.  3.
Help decipher the function(s) and mode of action of ABP in the testis and
epididymis.  These studies include cellular localization of the ABP
membrane receptor in testis and epididymis and mapping of the steroid-
binding domain of ABP by in vitro mutagenesis.  These studies also include
a search for ABP mutants by linkage analysis of the mouse ABP gene.
Studies of ABP gene expression in brain may provide new insights into ABP
function.

Our studies will contribute greatly to the knowledge of Sertoli cell gene
regulation and the function(s) of ABP, a major Sertoli cell secretory
protein.  This maintenance of spermatogenesis, and will aid in the
identification and possible treatment of fertility defects.

## Key facts

- **NIH application ID:** 2198318
- **Project number:** 5R01HD021744-08
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** DAVID R JOSEPH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $228,967
- **Award type:** 5
- **Project period:** 1986-12-01 → 1994-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198318

## Citation

> US National Institutes of Health, RePORTER application 2198318, HORMONAL REGULATION OF GENE EXPRESSION IN SERTOLI CELLS (5R01HD021744-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198318. Licensed CC0.

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