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Paracrine and Endocrine Influences on Gonadotrope Development and Function

Award Number: R01HD118024
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2031

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Paracrine and Endocrine Influences on Gonadotrope Development and Function - PROJECT SUMMARY/ABSTRACT The mechanisms by which gonadotropes coordinate in response to external cues to promote maximum female reproductive capacity are not known. The long-term goal of this project is to define the role of metabolism, specifically the adipokine leptin, in the development of the gonadotrope network in female mice. The overall objective is to define the pathways and regulators that promote the gonadotrope network to produce surge-level secretion of gonadotropins. The central hypothesis of this study is that leptin acts distinctly in the postnatal and adult female mouse to program gonadotrope network coordination, and that paracrine interactions with lactotropes support lifelong gonadotrope health. The rationale for this work lies in the potential to unveil the distinct developmental influences of leptin on the gonadotrope that will identify windows of sensitivity, specific molecular pathways, and transcriptional regulators important for normal female reproduction. The central hypothesis will be tested with studies outlined in the following two specific aims: (1) Define the role of gonadotrope leptin signals during the postnatal leptin surge, (2) Elucidate the key secreted factors that may mediate lactotrope-gonadotrope paracrine or gonadotrope-gonadotrope autocrine regulation and define the molecular mechanisms by which secretoneurin regulates gonadotropes. The Aim 1 studies revolve around two animal models in which gonadotrope leptin receptors are either deleted in the developing embryo or after the postnatal leptin surge. This allows us to study the importance of postnatal leptin to the development of gonadotropes. We will combine molecular single-cell analysis, calcium imaging, and analysis of reproductive capacity to determine the role of postnatal versus adult leptin signals in the ability of gonadotropes to develop and function as a network. In the second aim, we use a novel cell line and a series of conditioned media studies to dissect autocrine and paracrine interactions in the pituitary. We will utilize in vitro techniques to define the pathways by which secretoneurin stimulates LH production and secretion. The proposed research is innovative because it links a critical metabolic developmental window with the molecular programming of the gonadotrope cell network. It is significant because we expect to define novel regulators of gonadotropes and gain a better understanding of surge-level gonadotropin secretion.


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 = $443,348 )
2026	2026	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Child Health and Human Development Extramural Research	000	1	6/16/2026	NEW	$443,348
														Subtotal = $443,348

Grand Total All Awards = $443,348

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Paracrine and Endocrine Influences on Gonadotrope Development and Function

Award Number: R01HD118024

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2031

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