Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Investigating the role of central neurokinin-3 receptor signaling in the pathophysiology and treatment of polycystic ovary syndrome

Award Number: F31HD122465
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/18/2026
PERIOD OF PERFORMANCE END DATE: 05/17/2028

Group Awards By:

View Award Description

Investigating the role of central neurokinin-3 receptor signaling in the pathophysiology and treatment of polycystic ovary syndrome - PROJECT SUMMARY Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in individuals of reproductive age worldwide. Its exact pathophysiology remains unclear, and as a result, treatments for the condition are entirely symptom-based. However, there is evidence to suggest that dysregulation of neural circuitry is responsible for reproductive function in PCOS. Elevated luteinizing hormone (LH) release from the anterior pituitary is known to affect up to 75% of individuals with PCOS and suggests that PCOS patients also have elevated activity of hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Although the central mechanisms that lead to elevated LH pulsatile release have not been defined, a substantial body of clinical and basic research suggests that KNDy neurons in the arcuate nucleus of the hypothalamus are involved. KNDy cells are named for their co-expression of the neuropeptides kisspeptin, neurokinin B (NKB), and dynorphin and are hypothesized to play a critical role in GnRH/LH pulse generation. Specifically, the population is hypothesized to utilize NKB to drive synchronized activity of reciprocally connected KNDy cells, thereby inducing kisspeptin- mediated release of GnRH. Subsequently, dynorphin inhibits KNDy and GnRH cell activity to complete a GnRH/LH pulse. Recently, clinical trials using antagonists against the neurokinin-3 receptor (NK3R), the receptor with the highest affinity for NKB, have successfully reduced both elevated serum testosterone and elevated LH pulse frequency in PCOS patients, making NK3R a promising therapeutic for the condition. Although KNDy cells are a likely central target, the precise mechanism by which NK3R antagonism reduces LH release has not yet been tested. This proposal will test the hypothesis that NK3R antagonism impairs the generation of synchronized KNDy cell activity, which in turn reduces the generation of GnRH/LH pulses. In the proposed experiments, we will interrogate the effects of both acute and long-term pharmacological NK3R antagonism on KNDy cell activity, LH pulse generation, and reproductive outcomes in a prenatal androgen-induced mouse model of PCOS. Our first aim will be to determine the direct effects of NK3R antagonism on the activity and synchronization of KNDy cells. Here, we will employ in vivo calcium imaging with single-cell resolution and serial blood sampling to visualize these neurons and LH pulsatile release before and after administration of an NK3R antagonist in PCOS- like and control mice. Our second aim will use population-level in vivo calcium imaging and serial blood sampling to determine the effects of long-term NK3R antagonism on the KNDy network and LH pulses. We will also employ estrous cycle tracking and histological evaluation of ovarian tissue to determine the effects of NK3R antagonism on prenatal androgen-induced reproductive symptoms. Together, this research will provide novel insights into the role of NKB and its receptor in GnRH pulse generation and the utilization of this signaling mechanism to precisely target neuroendocrine dysfunction in PCOS.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $34,446 )
2026	2026	KENT STATE UNIVERSITY	1500 HORNING RD	KENT	OH	44242	PORTAGE	USA	Child Health and Human Development Extramural Research	000	1	5/7/2026	NEW	$34,446
2026	2026	KENT STATE UNIVERSITY	1500 HORNING RD	KENT	OH	44242	PORTAGE	USA	Child Health and Human Development Extramural Research	001	1	5/7/2026	NEW	$0
														Subtotal = $34,446

Grand Total All Awards = $34,446

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating the role of central neurokinin-3 receptor signaling in the pathophysiology and treatment of polycystic ovary syndrome

Award Number: F31HD122465

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/18/2026

PERIOD OF PERFORMANCE END DATE: 05/17/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer