# REGULATION OF LEYDIG CELL-SECRETED POLYPEPTIDES

> **NIH NIH R01** · POPULATION COUNCIL · 1994 · $197,000

## Abstract

Ultimately the primary function of all somatic cells in the testis is to
ensure a microenvironment that provides adequate androgen and nutritive
support for spermatogenesis and confers immunologic tolerance for the
mitotic spermatogonia located outside the blood-testis barrier. It is
well known that the pituitary hormones LH and PRL affect androgen
secretion by Leydig cells. What is less well understood is the identity
and function of the local peptidergic factors that make up the non-
steroidal microenvironment of the interstitium.

LACAF is an interstitial cell protein stimulated by HCG and growth
factor but inhibited by prolactin. LACAF activates adenylyl cyclase in
Leydig cells but this activation is not functionally directed towards
steroidogenesis. Such differential regulation is by known Leydig cell
trophic factors suggests that LACAF is an autocrine regulatory factor.
This protein shows some sequence homology with the testicular protein of
the VIP family of peptides that shares this capacity to activate cyclase
without concomitant effects on steroidogenesis. We will study the
function and regulation of these two proteins in parallel.

Prolactin preferentially enhances the secretion of two other
interstitial proteins, one of which is a known immunomodulator,
suggesting the prolactin affects testicular immune elements. The second
protein, PIL, may be a member of the transforming growth factor Beta
family of peptides. The physiological significance of this regulated
pattern of interstitial proteins is presently unknown. Our proposed
studies will focus on the unique features of the regulation of LACAF,
PIL and complement components by prolactin. The ability to determine the
various forms of the prolactin receptor MRNAS affords the opportunity to
determine the cell-specificity of these prolactin-induced changes in
interstitial protein secretion.

LACAF and PIL proteins will be further characterized. Cloned CDNAS for
these interstitial proteins will be isolated and their structure
characterized. Moreover, specific probes will be generated for use in
determining both physiological and aberrant expression of these proteins
in vivo and in vitro studies. Regulation of these interstitial proteins
will be studied by analysis of their MRNA levels as a function of
endocrine status using hybridization in situ and immunohistochemistry.
The mechanism(s) of action of these peptides will be investigated by
assessment of their effects on both seminiferous tubule and interstitial
cell function. This research plan will lead to new, significant data on
the mediators of intratesticular signalling and their physiological
relevance in the testis.

## Key facts

- **NIH application ID:** 2197270
- **Project number:** 5R01HD016149-09
- **Recipient organization:** POPULATION COUNCIL
- **SAM.gov UEI:** WKTLM8NNXDW1
- **Principal Investigator:** PATRICIA L. MORRIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $197,000
- **Award type:** 5
- **Project period:** 1982-09-30 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197270

## Citation

> US National Institutes of Health, RePORTER application 2197270, REGULATION OF LEYDIG CELL-SECRETED POLYPEPTIDES (5R01HD016149-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197270. Licensed CC0.

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