# Hypothalamic gating of the anorexic effects of estradiol

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $519,264

## Abstract

PROJECT SUMMARY
 The overall goal of this proposal is to understand sex differences in the neural regulation of feeding,
specifically how the anorexogenic effects of estradiol are modulated by a new hypothalamic node of the feeding
circuit. Previous research identified somatostatin (SST)-producing neurons as part of the neural circuit that
controls feeding, but sex differences were not explored. We find that activating SST neurons in the region that
spans the tuberal and ventromedial nuclei of the hypothalamus increases feeding in male and female mice.
However, ablating these neurons decreases feeding only in females, only during the high-estrogen phase of the
estrous cycle, and only when their body mass is relatively low. These findings are consistent with previous
studies but go further to reveal a context-dependent role for SST neurons in the regulation of feeding. We
hypothesize that SST neurons of the tuberal nucleus are a sex-specific, modulatory node within the brain that
can mask the anorexic effects of estradiol when energy reserves are low. The proposal outlines studies in mice
to determine how SST neuronal function is modulated by both reproductive and metabolic cues. In Aim 1, we
use cell-specific manipulations combined with gonadal hormone manipulations to reveal how SST neuron
function is modulated by reproductive state. In Aim 2, we use cell-specific manipulations combined with
manipulations of body mass and adiposity to reveal how SST neuron function is modulated by metabolic state.
In Aim 3, we use fluorescent labeling and flow cytometry followed by RNA-sequencing (flow-Seq) to assess how
SST neurons may be responsive to reproductive and metabolic conditions and whether this differs by sex.
Together, these studies will help us understand how neural circuits integrate multiple peripheral signals to fine
tune behavior and physiology across dynamic states.

## Key facts

- **NIH application ID:** 10743655
- **Project number:** 1R01DK136073-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Stephanie Correa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $519,264
- **Award type:** 1
- **Project period:** 2023-08-23 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10743655

## Citation

> US National Institutes of Health, RePORTER application 10743655, Hypothalamic gating of the anorexic effects of estradiol (1R01DK136073-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10743655. Licensed CC0.

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