1. Sponsor Organization: National Science Foundation

2. Project Title: Neural Substrates for Glucoprivic Regulation of Reproductive Hormone Secretion

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

The goal of the research to be performed with this NSF POWRE funding is to explore the link between energy balance and reproduction. This project is particularly suited for a POWRE award because it will allow exploratory work to determine the feasibility of a new line of inquiry. Sufficient metabolic fuels are necessary for successful reproduction in female mammals. Because metabolic imbalance initiates physiological and behavioral responses that restore energy homeostasis and allocate available fuels for life-sustaining processes, high-energy activities such as reproduction are often impaired. While decreases in reproductive hormone secretion during energy deficits reflect hypothalamic gonadotropin-releasing hormone (GnRH) dysfunction, the neural mechanisms that link substrate fuel homeostasis with neuroendocrine function are not clear. Recent studies show that intracerebral administration of the glucose anti-metabolite, 2-deoxy-glucose (2DG), inhibits plasma luteinizing hormon e (LH) concentrations, thus implicating central glucoprivic receptors in the regulation of reproductive hormones. Reports that circulating LH is inhibited by infusion of 2DG into the fourth ventricle suggest that interoreceptors of functional significance for reproductive function occur within a diffusion range of this delivery site, but the specific location(s) of these receptors in this part of the brain are unknown. Glucose-sensitive neurons may exist more rostrally within the ventromedial hypothalamus nucleus (VMN) and lateral hypothalamic area (LHA), but the role of these loci in compensatory reductions in reproductive hormone secretion during glucose substrate imbalance has not been studied. This proposal seeks to characterize the neuroanatomical distribution of central glucoprivic receptors that inhibit preovulatory LH secretion in intact female rats, and to identify hypothalamic structures that contain neurons critical for reproductive endocrine responses to glucose substrate imbalance. The PI p roposes to identifity the origin of central glucoprivic signals that inhibit phasic gonadotropin secretion by investigating the effects of site-specific infusion of 2DG into discrete brain loci on the onset, magnitude, and duration of the preovulatory LH surge in intact, adult female rats. She will also investigate whether the functional integrity of several discrete hypothalamic structures is critical for glucoprivic inhibition of the reproductive neuroendocrine axis by examining whether reversible pharmacological inhibition of local cellular function by colchicine attenuates inhibitory effects of glucose anti-metabolites on gonadotropin secretion. Other experiments will determine if specific neuropeptide neurons are critical for gonadotropin responses to 2DG.

5. References:

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6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal, Rodent
• Study Type:
  • In Vivo
  • Laboratory Study
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Neurological
  • Reproductive
• Hormonal Measures:
  • Peptide Hormones
  • Sex Steroids
• Level Of Study:
  • Physiology
  • Biochemistry
• Chemistry Metabolism:
  • Analyte Detection
  • Analyte Quantification
• Life Stage:
  • Female
  • Adult
• Risk Assessment:

10. Chemical Agents:

11. Performing Institution:

• Washington State University ;

12. Contact:

Institution: Washington State University
Division:
Given Name:
Name: Karen P Briski
Title:
Form:
E-Mail: kpb@vetmed.wsu.edu
Phone: 509/335-9661
Fax:
Street: Business Grants Office
Zip:
City: Pullman, WA 99164-3140
State:
Country:

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