# STEROID HORMONE CONTROL OF PROLACTIN GENE EXPRESSION

> **NIH NIH R29** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 1993 · $100,350

## Abstract

We will characterize the molecular mechanisms through which
estrogen and progesterone regulate the expression of the prolactin
gene.  These studies will further our understanding of the
interrelationships between these hormones in the control of normal
growth, development, and reproductive function, and may provide
insights into how estrogen and progesterone, through their effects
on prolactin gene expression, contribute to the development of
mammary cancer.  We have shown that estrogen stimulates prolactin
gene transcription through both direct and indirect pathways.  In
Specific Aim I, we will test the hypothesis that estrogen
indirectly stimulates prolactin gene transcription by inhibiting
the release of dopamine from the hypothalamus.  This will be done
directly by pituitary and the turnover of within the
tuberoinfundibular neurons of the hypothalamus, and indirectly by
examining the effects of estrogen on prolactin gene transcription
in pituitaries that have been transplanted under the Kidney
capsule.  Our preliminary data support a physiological role of
progesterone in the regulation of prolactin gene expression.  In
Specific Aim 2, we will examine in Vivo and in Vitro the regulation
of prolactin gene expression by progesterone, and the interactions
between progesterone and estrogen in this regulation.  In these
experiments the rate of the gene transcription will be quantified
by a nuclear transcription assay, mRNA level by slot or northern
blot procedures, and rate of prolactin synthesis by
immunoprecipitation of pulse-labeled prolactin.  In all
experiments, the expression of the closely related growth hormone
gene will also be examined as a control.  If regulation by these
steroid hormones is observed at the transcriptional level, the
control elements which confer this responsiveness will be
identified in experiments where various regions of the prolactin
gene domain are linked to the bacterial CAT gene and the fusion
genes are transfected into hormone-responsive cells.  In Specific
Aim 3, we will define the physiological roles of estrogen and
progesterone in regulating the expression of the prolactin gene
during the estrous cycle of the rat, and identify the levels at
which these hormones function in this regulation.  In these
experiments, the rate of transcription of the prolactin gene, the
level of prolactin mRNA and the rate of prolactin synthesis will
be examined throughout the course of the estrous cycle and the
effects of antiestrogens and antiprogestins on these parameters.

## Key facts

- **NIH application ID:** 2199072
- **Project number:** 5R29HD024189-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **SAM.gov UEI:** G15AG3BLLMH4
- **Principal Investigator:** JAMES D SHULL
- **Activity code:** R29 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $100,350
- **Award type:** 5
- **Project period:** 1989-01-01 → 1994-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199072

## Citation

> US National Institutes of Health, RePORTER application 2199072, STEROID HORMONE CONTROL OF PROLACTIN GENE EXPRESSION (5R29HD024189-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199072. Licensed CC0.

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