# LH ACTION IN OVARIAN CELL DIFFERENTIATION

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1994 · $178,832

## Abstract

Ovulation and luteinization are two processes which are induced in
preovulatory ovarian follicles as a consequence of the LH surge.
Ovulation is preceded by a pronounced but transient increase in
prostaglandin endoperoxide H synthase (PGS) the rate-limiting enzyme for
synthesis of prostaglandins.  We have recently purified this novel LH-
induced enzyme (M(r)=72,000; PGS72; PGSi) and shown that it is
immunologically and biochemically distinct (based on N-terminal amino
acid sequence, enzymatic activity and tryptic digests) from the other
isoform of the enzyme (M(r)=69,000; PGS69) which is present in many
tissues, such as uterus, kidney and heart.  Luteinization, on the other
hand, is associated with a rapid but sustained increase in cholesterol
side-chain cleavage cytochrome P450 (P450scc).  LH-induction of
luteinization is established within 7h of exposure of preovulatory
follicles to LH/FSH in vivo or in vitro.  Following this exposure to
hormones, luteinization can proceed and be maintained in vitro in the
absence of hormones.  Thus, in association with luteinization regulation
of the P450scc gene appears to shift from cAMP-dependent to cAMP-
independent mechanisms.  The cellular signalling pathways which determine
the responses of granulosa cells to ovulatory levels of gonadotropins
have yet to be clearly defined but appear to involve distinct pathways.
For example, we have recently shown that ovulatory but not basal
concentrations of LH and FSH induce both PGSi and P450scc.  In contrast,
gonadotropin releasing hormone (GnRH) can mimic LH-induction of PGSi but
not P450scc.  Tyrphostins (inhibitors of tyrosine kinases) block LH and
GnRH induction of PGSi and prevent LH stimulation of luteinization and
constitutive expression of P450scc.  Although the cAMP-A-kinase pathway
appears to play a primary role in mediating LH action, tyrosine kinases
may also be involved.  To characterize the hormonal regulation of PGSi
and P450scc expression, we have isolated both genes, sequenced 5'
flanking regions containing putative promoter elements and have begun
characterizing the functional activity of these promoters.  Therefore,
the specific aims of the proposed research are:  (1) to determine the
molecular mechanisms involved in LH-mediated transient induction of the
novel, distinct isoform of prostaglandin endoperoxide synthase (PGSi);
(2) to determine the molecular mechanisms by which LH induces P450scc and
its sustained expression in luteal cells and (3) to determine the
specific cellular signalling pathways by which LH mediates induction of
PGSi (ovulation) and P450scc (luteinization).  Understanding the
regulation of these genes should provide greater insight into the events
controlling ovulation and luteinization, and perhaps the broader areas
of inflammation and terminal cell differentiation, respectively.

## Key facts

- **NIH application ID:** 2197278
- **Project number:** 5R01HD016229-13
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** JoAnne Stewart Richards
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $178,832
- **Award type:** 5
- **Project period:** 1982-03-01 → 1998-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197278

## Citation

> US National Institutes of Health, RePORTER application 2197278, LH ACTION IN OVARIAN CELL DIFFERENTIATION (5R01HD016229-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197278. Licensed CC0.

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