# MATERNAL-FETAL STEROID REGULATION

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 1994 · $468,816

## Abstract

In human and nonhuman primate pregnancy, progesterone (P4) and estrogen
synthesized within the placenta and cortisol (F) produced by the fetal
adrenal late in gestation play major roles in pregnancy maintenance and
maturation of the fetus.  The applicants have shown that estrogen plays a
central integrative role in regulating placental P4 synthesis and in
initiating de novo F synthesis by the fetal adrenal near term by modulating
trans-placental F and cortisone (E) metabolism, which we propose activates
the fetal hypothalamic-hypophyseal-adrenocortical axis (HPAA).  The
proposed consortium study will employ in vivo experimental paradigms in
pregnant baboons and molecular biological methodologies to test the
hypotheses that:  [1] a developmental regulation of P4 biosynthesis exists
which involves enhanced expression/translation of the mRNAs for the low
density lipoproteins (LDL) receptor and mitochondrial cytochrome P450
cholesterol side-chain cleavage (scc) enzyme system within the placenta by
estrogen; [2] the ontogenesis of fetal adrenal F production elicited by
estrogen-induced alterations in transplacental F and E metabolism results
from activation of corticotrophin releasing hormone (CRH)-ACTH production
by the fetal hypothalamus-pituitary; and [3] that the increase in
activities of the enzymes 17alpha-hydroxylase/17-20 lyase (17alpha-OHase)
and delta5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) catalyzing de
novo F production by the fetal adrenal near term, which result from
activation of the HPAA by estrogen-induced changes in placental F-E
metabolism, is the result of enhanced expression/translation of the mRNAs
for these enzymes by fetal pituitary ACTH.  In Study I, placental mRNAs and
levels of LDL receptor and P450scc/adrenodoxin will be quantified by
Northern/slot hybridization and Western immunoblot analyses, respectively,
in baboons of early, mid and late gestation when estrogen is normally
increasing, late in gestation following suppression of estrogen production
by fetal hypophysectomy to remove ACTH-dependent C19-steroid precursors,
and at midgestation in animals in which estrogen has been elevated by
maternal administration of estradiol.  In Experiment II-1, pituitary ACTH
production will be determined by in vitro perifusion and expression of CRH
and POMC mRNAs measured by quantitative in situ hybridization of
hypothalamic/pituitary tissue obtained from baboon fetuses in which
estrogen has been elevated and de novo F production initiated prematurely
at midgestation and confirmed by analysis of adrenal steroidogenesis by in
vitro perifusion.  The importance of fetal ACTH per se to the initiation of
de novo F production will be determined by treating baboon fetuses in utero
with ACTH at midgestation.  In Experiment II-2, the mRNAs (Northern/slot
blot) for and peptide levels (Western immunoblot) of 3beta-HSD and 17alpha-
OHase will be quantified in fetal adrenals obtained at midgestation
following administration of estrogen or t...

## Key facts

- **NIH application ID:** 2196995
- **Project number:** 5R01HD013294-14
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **SAM.gov UEI:** Z9CRZKD42ZT1
- **Principal Investigator:** Eugene D. Albrecht
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $468,816
- **Award type:** 5
- **Project period:** 1980-07-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196995

## Citation

> US National Institutes of Health, RePORTER application 2196995, MATERNAL-FETAL STEROID REGULATION (5R01HD013294-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196995. Licensed CC0.

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