# FREE PLASMA SEX HORMONE AND ANDROGEN ACTION

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1994 · $156,717

## Abstract

Sebaceous cell growth and differentiation is regulated mainly by
androgen, retinoids, and poorly understood developmental biological
factors.  Our overall hypothesis is that sebocytes go through specific
unidirectional developmental stages, which are each responsive in a
specific manner to specific hormonal and stromal signals.  The cell types
consist of undifferentiated cells and their early-, mid, late, and
terminally differentiated progeny.

We will begin by characterizing sebocyte stages and substages precisely
by fluorescent in situ hybridization (FISH) using molecular markers for
mRNA's to co-localize cellular androgen receptor (AR), 5alpha-reductase
(5alpha-R), the lipogenic enzymes HMG-CoA reductase (HMGR) and acetyl-CoA
carboxylase (ACC), cytokeratin 4 (K4), retinoic acid receptor (RAR), and
the retinoid X receptor (RXR).  The hypothesis will then be tested that
sebocyte stages can be precisely characterized by these molecular
characteristics and that sebocytes will go through these early
differentiated stages in monolayer culture.

Androgen is specifically hypothesized to a) indirectly stimulate
undifferentiated preputial cells to proliferate, via an action on
preputial stromal cells, and b) directly act on early differentiated
sebocytes to inhibit their proliferation, but induce lipid synthesis.
We expect that and androgen receptor (AR) and 5alpha-R mRNA will not be
expressed in undifferentiated sebocytes, and that they will be expressed
in high amounts in preputial fibroblasts.  The effects of androgen on
lipid synthesis are expected to correspond to increased expression of AR
mRNA and subsequent induction by androgen of lipogenic enzyme mRNA's in
an early differentiated subpopulation of sebocytes.  Retinoic acid (RA)
is hypothesized to act directly on an early differentiated subtype of
sebocyte to interfere with androgen action by inhibiting both their
proliferation and lipogenesis.  We will determine whether full
differentiation of sebocytes occurs in lifted raft cultures due to the
generation of a concentration gradient of RA such that reduced RA levels
in supranasal layers permits terminal differentiation of sebocytes.

Methodology to be employed is that in use in this laboratory: epithelial
cell culture using monolayer and raft technique, histology,
histochemistry, Northern analysis, immunocytochemistry, fluorescence
microscopy, and RNase protection assay.  The latter techniques will be
combined in the form of FISH.

## Key facts

- **NIH application ID:** 2194964
- **Project number:** 2R01HD006308-20A2
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** ROBERT L ROSENFIELD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $156,717
- **Award type:** 2
- **Project period:** 1978-07-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194964

## Citation

> US National Institutes of Health, RePORTER application 2194964, FREE PLASMA SEX HORMONE AND ANDROGEN ACTION (2R01HD006308-20A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194964. Licensed CC0.

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