# Neuroendocrine Regulation of Reproduction by Glucocorticoids

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $321,625

## Abstract

Project Summary/Abstract
The overall goal of this research is to understand how stress disrupts reproductive function and fertility. The
impact of stress within our society is widespread; over 75% of Americans report frequently experiencing
physical symptoms attributed to stress. In women, stress is considered a major factor in the development of
menstrual cycle disorders, amenorrhea, and infertility, affecting 25% of reproductive age women. To date, the
neuroendocrine causes of stress-induced infertility are not completely understood. Several pathways within the
brain are activated by stress. The hypothalamic-pituitary-adrenal (HPA) axis is a common and critical response
to all stressors. The HPA axis controls circulating glucocorticoids. Though glucocorticoids have been
considered a key mediator of stress-induced reproductive suppression, little is known about the precise
location(s) or mechanism(s) by which glucocorticoids diminish GnRH or gonadotropin secretion, either in
response to stress in normal women or in conditions of glucocorticoid excess, such as Cushing’s syndrome.
Preliminary studies in our laboratory demonstrate that a stress-like increment in corticosterone, the natural
glucocorticoid in rodents, can disrupt the ovulatory cycle of the female mouse. Furthermore, stress levels of
glucocorticoids can reduce mean plasma luteinizing hormone (LH) or can block the preovulatory LH surge in
females. In theory, either a reduction in mean LH, presumably reflecting a suppression in LH pulses, or
interference with LH surge generation could contribute to ovulatory cycle disruption in the female, because
pulsatile LH secretion is necessary for estradiol production as an early step in the chain of endocrine events
which leads to the preovulatory LH surge. We do not yet know how corticosterone disrupts LH pulses in
females and if this mechanism differs in males. Nor do we know if elevated corticosterone is necessary for
disruption of the ovulatory cycle or fertility in males and females in response to stress. These are major goals
of this proposal, tested by the following overall hypothesis: Enhanced secretion of corticosterone during stress
disrupts reproductive neuroendocrine function in males and females by impairing the regulation of LH pulses
and/or the preovulatory LH surge via inhibition of kisspeptin (Kiss1) and gonadotropin-releasing hormone
(GnRH) neuronal activation and decreased gonadotrope responsiveness to GnRH. Aim 1 will determine how a
stress level of corticosterone inhibits the preovulatory LH surge. Aim 2 will determine the mechanism(s)
whereby elevated glucocorticoids suppress GnRH and LH pulses. Aim 3 will assess the necessity of GR
signaling for stress effects on reproduction. Results from this proposal have the potential to lead to discoveries
in management and treatment of menstrual cycle disturbances and infertility, as well as, optimized treatment or
improved outcome for those couples requiring assisted reproductive tec...

## Key facts

- **NIH application ID:** 9895818
- **Project number:** 5R01HD086100-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** KELLIE Breen Church
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,625
- **Award type:** 5
- **Project period:** 2016-08-10 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895818

## Citation

> US National Institutes of Health, RePORTER application 9895818, Neuroendocrine Regulation of Reproduction by Glucocorticoids (5R01HD086100-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9895818. Licensed CC0.

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