# Metabolic Regulators of Corpus Luteum Function

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2021 · $304,148

## Abstract

SUMMARY
The corpus luteum (CL) is a transient endocrine gland whose structure and function are regulated by both
luteotrophic factors that stimulate luteal function and luteolytic factors that inhibit luteal function. The CL is the
primary source of progesterone during estrous or menstrual cycles and early pregnancy. If pregnancy does
not occur, timely regression of the CL is required to resume normal estrous or menstrual cycles. The single
most important factor involved in regulating the secretion of progesterone in the CL, irrespective of species,
is luteinizing hormone (LH). This pituitary gonadotropin induces formation of the CL, and is capable of
extending the functional life span of the CL. Secretion of progesterone is absolutely required for establishment
and maintenance of pregnancy and inadequate progesterone secretion contributes to early pregnancy loss
in women and cattle, the two model systems employed in this project. Female reproduction is affected by
obesity and it is estimated that over half of reproductive age women are overweight or obese. Recent research
suggests that weight gain can contribute to impaired function of the primate CL. Recent developments in other
fields of research have shed light on the composition and role of intracellular lipid droplets (LD) as significant
contributors to metabolic events and disease states. These understudied organelles are prominent
components of steroidogenic cells but almost nothing is known about their role in the ovary and specifically
their role in luteal function. A deeper understanding of the metabolic regulation of the CL has important
implications for improving fertility. Lipid droplets accumulate during CL formation, presumptively for storage
of the steroid precursor, cholesterol, and cellular energy in the form of fatty acids. Our preliminary data indicate
that the lipid droplet may serve as a signaling platform for steroidogenesis and metabolism in the luteal cell.
Furthermore the lipid droplet appears to be differentially regulated by luteotrophic and luteolytic hormones.
There is a gap in our knowledge of the formation, composition, and function of LDs in ovarian steroidogenic
cells. This proposal will test the hypothesis that LDs provide a metabolic or hormone-sensitive organelle which
can provide cellular energy and/or store and mobilize substrate for progesterone synthesis. Furthermore, we
hypothesize that the natural luteolysin PGF2α rapidly disrupts LD dynamics in vivo resulting in an acute
inhibition of steroidogenesis. The project will employ state-of-the-art lipidomics and proteomics analysis to
examine LDs and metabolic events driven by LH or PGF2α in bovine luteal cells and human granulosa-luteal
cells. Our long-term objectives are to fully understand the cellular mechanisms of action of gonadotropins and
the regulation of fertility. The short-term goals of this research are to discover new signaling events initiated
by LH and PGF2α and to determine how these novel m...

## Key facts

- **NIH application ID:** 10155086
- **Project number:** 5R01HD092263-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** JOHN S DAVIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $304,148
- **Award type:** 5
- **Project period:** 2017-08-03 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155086

## Citation

> US National Institutes of Health, RePORTER application 10155086, Metabolic Regulators of Corpus Luteum Function (5R01HD092263-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10155086. Licensed CC0.

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