This proposal is in response to RFA-HD-09-008 Cooperative Research Partnerships to Promote Workforce Diversity in the Reproductive Sciences (U01), entitled, Kisspeptin Regulation and GPR54 Signaling in Reproduction. The application is a research partnership among Drs. Sally Radovick and Andrew Wolfe at Johns Hopkins University School of Medicine and Dr. Gloria Hoffman at Morgan State University. Undergraduate students from Morgan State University and Johns Hopkins University will be recruited and mentored under this collaborative award mechanism. The curriculum will include didactic lectures, a wide breadth of laboratory based studies and career counseling. A Steering Committee comprised of the investigators will guide the process. The release of LH is under the regulation of the neurohormone, luteinizing hormone releasing hormone (LHRH). Recently, the peptide kisspeptin (KP) that signals through a G-protein coupled receptor, GPR54, was found to be a key component in the regulation of LHRH. Evidence for a direct role for KP at the level of the LHRH neuron comes from anatomical and in vitro studies in LHRH expressing ceil lines. Two principal populations of KP neurons are described in the hypothalamus: one in the arcuate nucleus (Arc) and one in the AVPV. The AVPV KP neurons project directly to LHRH neurons and stimulate LHRH neurons at the time of an LH surge. The Arc population is not sexually dimorphic and is implicated in basal LHRH release and negative feedback in both sexes, but how it does so is unknown. While some aspects of KP regulation are preserved in primates, there is little resolution as to whether the AVPV population is present, and whether connections of the KP neurons to LHRH and other systems are preserved across species. This proposal will examine the connectivity of KP neurons with the LHRH system in rodents vs. primates and will also generate a floxed GPR54 mouse line to specifically ablate GPR54 in the LHRH neuron to study pubertal onset and estrogen feedback regulation in addition to cellular changes in LHRH neurons. In summary, this proposal will delineate both the role of KP-GPR54 signaling in estrogen feedback regulation and its locus in the central reproductive axis.

Public Health Relevance

The goal is to provide selected undergraduates the unique resources available from two institutions focused on a broad spectrum of didactic and laboratory experiences in the field of reproductive biology. Partnering to learn with academic researchers, the students will study regulatory mechanisms controlling mammalian reproduction.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HD066435-03
Application #
8305093
Study Section
Special Emphasis Panel (ZHD1-DSR-L (08))
Program Officer
Ravindranath, Neelakanta
Project Start
2010-08-17
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$285,719
Indirect Cost
$139,225
Name
Morgan State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
879941318
City
Baltimore
State
MD
Country
United States
Zip Code
21251
Novaira, Horacio J; Sonko, Momodou L; Hoffman, Gloria et al. (2014) Disrupted kisspeptin signaling in GnRH neurons leads to hypogonadotrophic hypogonadism. Mol Endocrinol 28:225-38
Wu, Sheng; Divall, Sara; Nwaopara, Amanda et al. (2014) Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell. Diabetes 63:1270-82