# PRETRANSLATIONAL REGULATION OF FSH AND LH

> **NIH NIH R29** · UNIVERSITY OF COLORADO DENVER · 1993 · $79,586

## Abstract

Follicle stimulating hormone (FSH) and luteinizing hormone (LH) are
glycoprotein hormones, each comprised of two dissimilar subunits alpha
and beta, encoded for the separate genes on different chromosomes.
Although much is known concerning the regulation of the biosynthesis of
the subunits. The recent availability of cDNA probes for the rat
FSH(beta), LH(beta, and alpha subunits now permits and examination of the
differential regulation of FSH and LH gene expression at the
pretranslational level in different physiologic states and following
various endocrine manipulations.

There are 3 major objectives: 1) First, to define the normal physiology
of gonadotropin subunit gene expression in the female by examining the
ontogeny of gonadotropin synthesis: during gestation, in infancy and
across sexual development, during the estrous cycle and with aging in the
retired breeder. Then with this normative data as a backdrop, the role of
gonadal steroids and hypothalamic factors in the pretranslational control
of FSH and LH will be delineated. 2) The second aim of this proposal is
to examine the differential regulation of gonadotropin mRNA levels by sex
steroid hormones in the female rat. In vivo studies will examine the
effects of (a) the type of sex steroid replacement (estrogen vs.
progestin vs. androgen), (b) the dosage of steroid administration
(subphysiologic to supraphysiologic), (c) the impact of the time interval
following ovariectomy before replacement, and (d) the duration of steroid
replacement of FSH(beta), LH(beta), and alpha subunit mRNA levels.
Additionally, intact animals will receive steroid hormone antagonists as
an alternative approach to defining the role of gonadal steroids in the
regulation of gonadotropin subunit mRNAs. Concurrent in vitro rat
pituitary cell culture studies will explore similar paradigms to dissect
the locus of steroid action--either directly at the gonadotrope and/or
indirectly via effects on hypothalamic factors. The changes in subunit
mRNA levels in pregnancy will also be examined as a model of excessive
endogenous steroid milieu. 3) Third, the differential dependence of
gonadotropin subunit synthesis upon gonadotropin-releasing hormone (GnRH)
will be delineated. A potent GnRH gonadotropin secretion. In this model
of relative GnRH deficiency, the variable changes in FSH(beta), CH(beta),
in this GnRH-deficient model, specific sex steroids and/or gonadal
peptides will be reintroduced to determine their effects on the
biosynthesis and secretion of the gonadotropin subunits.

These proposed studies will expand our understanding of the normal
physiology of the reproductive axis in the female. Additionally, they
will impact on the design of future fertility and contraceptive agents
and potential therapeutic interventions for reproductive disorders and
hormone responsive malignancies.

## Key facts

- **NIH application ID:** 2199485
- **Project number:** 5R29HD025275-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** Margaret E Wierman
- **Activity code:** R29 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $79,586
- **Award type:** 5
- **Project period:** 1989-08-01 → 1995-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2199485

## Citation

> US National Institutes of Health, RePORTER application 2199485, PRETRANSLATIONAL REGULATION OF FSH AND LH (5R29HD025275-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2199485. Licensed CC0.

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