# Investigation of Anatomical and Functional Mechanisms Underlying the Suppression of Gonadotropin Secretion by Metabolic Stress

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $38,388

## Abstract

PROJECT SUMMARY
Stress is a leading cause of functional hypothalamic amenorrhea and infertility. Amenorrhea is associated with
cardiovascular disease, osteoporosis, and mental health, therefore elucidation of the mechanisms by which
stress suppresses gonadotropin secretion may provide new avenues to protect against chronic illnesses.
Metabolic stress occurs in healthy people as well as in several disease states. Insulin-induced hypoglycemia
(IIH) is a reliable, repeatable and quantifiable model of acute metabolic stress that suppresses pulsatile
luteinizing hormone (LH) secretion; however, the mechanisms that mediate the suppression of LH are not
known. This proposal will use genetic, pharmacologic and molecular approaches to test the hypothesis that
urocortin 2 cells in the paraventricular nucleus (PVN) are innervated by brainstem norepinephrine neurons, and
project onto and inhibit kisspeptin neurons in the arcuate nucleus to suppress pulsatile LH secretion in IIH. In
Aim 1, we will determine if urocortin 2 cells in the PVN receive anatomical and functional input from brainstem
norepinephrine neurons during IIH. In Aim 2, we will determine if kisspeptin cells receive anatomical and
functional input from urocortin 2 neurons in the PVN during IIH. In Aim 3, we will characterize the effects of
urocortin 2 on ARC kisspeptin neuron function in an immortalized hypothalamic kisspeptin-expressing cell line.
This project will examine the form and function of a brainstem-PVN-arcuate nucleus neural circuit to inhibit
pulsatile LH secretion during metabolic stress. These experiments will test an innovative hypothesis involving
urocortin 2 signaling that will advance our knowledge of integrated stress responses, regulation of
gonadotropin secretion, and provide the applicant training in critical skills that will be necessary for a
successful career in academic research.

## Key facts

- **NIH application ID:** 10267661
- **Project number:** 5F32HD096811-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Richard Bryan McCosh
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $38,388
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10267661

## Citation

> US National Institutes of Health, RePORTER application 10267661, Investigation of Anatomical and Functional Mechanisms Underlying the Suppression of Gonadotropin Secretion by Metabolic Stress (5F32HD096811-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10267661. Licensed CC0.

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