SHORT-TERM STARVATION DECREASES POMC MESSENGER-RNA BUT DOES NOT ALTER GNRH MESSENGER-RNA IN THE BRAIN OF ADULT MALE-RATS

Dietary restriction reduces circulating gonadotropin and testosterone levels in male rats, an effect thought to be mediated through reduced gonadotropin-releasing hormone (GnRH) secretion; however, the cellular mechanisms subserving this response are still unknown. We reasoned that if dietary restriction reduces GnRH secretion, this would be reflected by a decrease in GnRH synthesis and likewise cellular GnRH mRNA levels. We tested this hypothesis by comparing cellular levels of GnRH mRNA between ad libitum fed (n = 4) and starved (n = 4) adult male rats. Five days of starvation resulted in a 21% decrease in body weight and an 85% decline in serum testosterone levels (fed: 13.9 +/- 2.00 vs. starved: 2.1 +/- 0.70 nmol/l; p < 0.01). In situ hybridization and image analysis demonstrated that short-term starvation influenced neither GnRH cell number (fed: 148 +/- 16 vs. starved: 157 +/- 13 cells) nor cellular GnRH mRNA signal level (fed: 177 +/- 5 vs. starved: 160 +/- 7 grains/cell) in any region of the basal forebrain. Endogenous opioid peptides are known to exert an inhibitory effect on GnRH secretion and have been implicated in having a role in the starvation-induced effects on the reproductive system. We therefore also tested the hypothesis that alterations in proopiomelanocortin (POMC) gene expression are involved in the neuroendocrine response to starvation, by comparing cellular POMC mRNA levels in individual neurons (almost-equal-to 160 neurons/animal) of the arcuate and periarcuate nuclei between fed control (n = 4) and starved (n = 4) adult male rats. In contrast to the lack of effect on GnRH mRNA, starvation induced a 24% decline in cellular POMC mRNA signal levels (fed: 108 +/- 6 vs. starved: 82 +/- 5 grains/cell; p < 0.05), which was most pronounced in the anterior aspect of both the arcuate and periarcuate nuclei. Based on these results we conclude that (1) alterations in GnRH gene expression do not play a significant role in the suppression of gonadotropin secretion during food restriction, and (2) starvation causes a reduction in brain POMC gene expression, an effect possibly mediated by reduced circulating testosterone levels.