# STEROID ACTION AT THE OOCYTE PLASMA MEMBRANE

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 1994 · $148,695

## Abstract

Progesterone binding at the amphibian oocyte plasma membrane induces
meiosis via synthesis of the maturation promoting factor, now recognized
to be a universal mitogen.  This proposal is concerned with the mechanism
of steroid action at the plasma membrane which leads to mitogen
synthesis.  We have found that the following reactions are triggered by
progesterone in isolated oocyte plasma membranes:
phosphatidylethanolamine (PE) N-methylation (within seconds), the release
of protease and free Ca2+, a rise and fall in 1,2-diacylglycerol (DAG)
derived from phosphatidycholine (PC) by phospholipase C (PLC) (within two
minutes), activation of protein kinase C (PKC) and increased inositol
phosphate turnover.  Phospholipid N-methylation, leading to PC synthesis,
occurs only within plasma membranes, but 80-90% of the DAG, which
activates PKC and is now recognized as a second messenger, is generated
from PC.  This represents the transduction of a plasma membrane receptor
signal to second messenger activation at intracellular membranes.  The
mechanism by which steroid binding to the plasma membrane receptor
activates an enzyme may be G protein-mediated, since our experiments
indicate that G proteins directly regulate plasma membrane N-
methyltransferase and/or phospholipase C.  The first specific aim of this
proposal is to use photoaffinity labeling to identify G proteins which
are functionally associated with the progesterone receptor; the ultimate
goal being to reconstitute the hormone-receptor-G protein system in
membrane vesicles.  The second aim is to determine the molecular species
and phospholipid source of the DAGs generated both from plasma membrane
and intracellular membranes.  About 30% of the total [3H]-glycerol-
labeled 1,2--DAG in the prophase oocyte is derived from plasmalogen, a
choline phospholipid containing an alpha, beta-unsaturated ether linkage
in the 1-position, high in sperm and excitable tissues (brain, heart).
The third aim is to investigate transient changes in diacylglycerol
kinase activity after hormone stimulation; this enzyme controls both DAG
levels and the branch point promoting resynthesis of
phosphatidylinositols at the expense of resynthesis of the major membrane
phospholipids such as PC.  The fourth aim is to examine the possible role
of PKC-dependent protein phosphorylation and/or decreased membrane
fluidity in the down-regulation of adenylate cyclase.  The proposed
research should contribute to the understanding of mitogenic signaling,
steroid hormone action at the plasma membrane, and role of phospholipids
in generating a second messenger, and the spread of that second messenger
signal from plasma to intracellular membranes.

## Key facts

- **NIH application ID:** 2196723
- **Project number:** 5R01HD010463-11
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** GENE A MORRILL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $148,695
- **Award type:** 5
- **Project period:** 1977-02-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2196723

## Citation

> US National Institutes of Health, RePORTER application 2196723, STEROID ACTION AT THE OOCYTE PLASMA MEMBRANE (5R01HD010463-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2196723. Licensed CC0.

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