# PHYSIOLOGICAL ROLE OF PITUITARY ER MRNA VARIANTS

> **NIH NIH K11** · UNIVERSITY OF VIRGINIA · 1994 · $88,017

## Abstract

Physiological Role of Pituitary ER mRNA Variants  The estrogen receptor
(ER) is a ligand-activated transcriptional regulatory protein with
discrete functional domains.  Recent studies have demonstrated that its
structural integrity is critically important in governing cellular
function.  Though most variant ER mRNA forms have been found in
neoplastic tissues, our laboratory has recently identified an ER message
in normal rats which is pituitary-specific.  This ER mRNA comprises
about 20% of the total ER message in rat pituitary and represents the
only variant ER mRNA identified in normal rat tissue to date.
Preliminary structural comparison between the pituitary-specific form
(5.5kb) and the more ubiquitous form (6.2kb) has demonstrated that
approximately 400 bp of the 700 bp size difference between them occurs
in the 5' untranslated or coding regions of the message.  The pituitary-
specific message also appears to be expressed in mature female rats but
not in mature males.  Studies in this proposal are designed to further
define the molecular structure and physiological significance of the
pituitary-specific ER mRNA, and to investigate the ER status of human
pituitary tissue.  In the rat, ribonuclease H experiments will be
performed to provide gross structural information about the 5'
untranslated and polyadenylate tails of the two mRNAs.  A polyadenylate
enriched randomly primed rat pituitary cDNA library will be screened in
order to clone and sequence the pituitary-specific form.  The absolute
and relative amounts of each ER mRNA will be determined in
ovariectomized and estrogen (E2) replaced mature females, in immature
females (basal and E2 stimulated) and in each stage of the estrous
cycle.  The significance of coding region differences between forms will
be evaluated by E2 and DNA binding studies of each message's in vitro
translation product.  The reverse hemolytic plaque assay and the
polymerase chain reaction (PCR) will be combined to determine if
particular anterior pituitary cell types contain the 5.5kb or 6.2kb
messages.  The above experiments, both structural and functional in
nature, should provide definitive information on the role of the 5.5kb
ER message.  Investigation into the ER status of human pituitary will be
two-fold.  First, autopsy samples will be collected and polyadenylated
RNA will be isolated to determine if a pituitary-specific of ER exists
in the human.  Second, the ER mRNA status of human pituitary tumors will
be determined using PCR (several different areas within the coding
region will be examined), and these results will be correlated with E2
binding data to determine if the presence or integrity of the ER is an
important factor in the regulation of tumor function or growth.

## Key facts

- **NIH application ID:** 2194466
- **Project number:** 5K11HD000982-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **SAM.gov UEI:** JJG6HU8PA4S5
- **Principal Investigator:** KEITH E FRIEND
- **Activity code:** K11 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $88,017
- **Award type:** 5
- **Project period:** 1992-03-01 → 1995-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194466

## Citation

> US National Institutes of Health, RePORTER application 2194466, PHYSIOLOGICAL ROLE OF PITUITARY ER MRNA VARIANTS (5K11HD000982-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194466. Licensed CC0.

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