# Deciphering the interactions of stress, corticosteroids, and Kiss1 neurons in reproduction and vasomotor symptoms in aging females

> **NIH NIH U54** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $388,190

## Abstract

PROJECT SUMMARY
Vasomotor symptoms (VMS), also known as hot flashes, are common perturbations of perceived high
temperature that women experience during menopause as a consequence of the depletion of estradiol levels.
These VMS entail profuse sweating and peripheral vasodilation that can adversely affect quality of life in
menopausal women, relevant to subsequent risk of cardiovascular disease and dementia. Recently, neurons
producing the neuropeptides kisspeptin (encoded by the Kiss1 gene), neurokinin B (NKB, encoded by Tac2),
and dynorphin (Dyn, encoded by Pdyn) and referred to as KNDy neurons in the hypothalamic arcuate nucleus
of mice have been identified as mediators of hot flashes through a common pathway that also controls pulsatile
GnRH secretion and the activity of the hypothalamic-pituitary-gonadal (HPG) axis. Based on this dual role of
KNDy neurons, we hypothesize that factors that negatively impact reproductive function, such as stress and
hypercortisolemia, act through KNDy neurons and will also affect thermoregulation (i.e., VMS) and sleep in
menopausal patients. To this end, using mouse models of menopause and VMS, we aim to: 1) determine if
these effects occur through direct regulation of Kiss1 or indirectly through regulation of Tac2 or Pdyn; and 2)
determine if these effects occur on the KNDy neurons themselves and/or via neurons upstream of KNDy
neurons—specifically, via GABAergic neurons. In addition, given the association of the menopausal decline of
sex steroids with not only VMS but also disruption of sleep patterns, we aim to explore the relationships of
stress, corticosteroids and KNDy neurons in the absence of sex steroids with sleep disruption. The successful
completion of this proposal will offer important new mechanistic insights into the roles and effects of stress on
KNDy neurons, the HPG axis, VMS, and associated sleep disturbances with the assistance of the Sleep Core.
These insights will be critical to inform the development of new, safer and more effective tools to mitigate the
effects of stress and of hot flashes in women, as studied in Project 1 and Project 2 of this SCORE application,
and thereby improve reproductive health aging outcomes in women.

## Key facts

- **NIH application ID:** 9854041
- **Project number:** 1U54AG062322-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Ursula B. Kaiser
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,190
- **Award type:** 1
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9854041

## Citation

> US National Institutes of Health, RePORTER application 9854041, Deciphering the interactions of stress, corticosteroids, and Kiss1 neurons in reproduction and vasomotor symptoms in aging females (1U54AG062322-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9854041. Licensed CC0.

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