Decreased Gonadotropin-Releasing Hormone Neuronal Activity Is Associated with Decreased Fertility and Dysregulation of Food Intake in the Female GPR-4 Transgenic Rat
Document Type
Article
Source
Endocrinology
ISSN
0013-7227
Volume
146
Issue
9
First Page
3800
Last Page
38008
Publication Date
9-2005
Department
Natural Sciences and Mathematics
Abstract
Expression of a cAMP-specific phosphodiesterase in GnRH neurons in the GPR-4 transgenic rat resulted in decreased LH levels and pulse frequency and diminished fertility. We have characterized changes in fertility, adiposity, and reproductive and metabolic hormones with age. Although LH levels were decreased in 3-, 6-, and 9-month-old GPR-4 females relative to wild-type (WT) controls, GPR-4 females did not become anovulatory until 6 months of age. No differences were observed in FSH, estradiol, or androstenedione levels in 3-, 6-, or 9-month-old GPR-4 and WT females. At 9 months of age, GPR-4 females had significantly increased abdominal and sc fat depot weights that were associated with increased leptin and insulin levels not observed in WT females. We tested the hypothesis that metabolic changes observed at 9 months of age were the result of dysregulation of the mechanisms controlling energy balance. Two-month-old female GPR-4 rats placed on a high-energy diet gained weight at a rate significantly greater than WT females and, after 24 d, developed the same metabolic phenotype observed in 9-month-old GRP-4 females (increased abdominal and sc fat associated with elevated leptin and insulin concentrations). Overeating did not correlate with changes in estradiol or androstenedione levels. We conclude that decreased GnRH neuronal activity is closely associated with decreased reproductive function and dysregulation of food intake.
Rights
Copyright © 2005 by The Endocrine Society
Publisher Statement
This article has been accepted for publication in Endocrinology. Published by Oxford University Press.
PubMed ID
15919747