Short-Term Starvation Decreases POMC mRNA but Does Not Alter GnRH mRNA in the Brain of Adult Male Rats

Abstract

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 pro-opiomelanocortin (POMC) gene expression are involved in the neuroendocrine response to starvation, by comparing cellular POMC mRNA levels in individual neurons (≈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.

N-acetylation of hypothalamic α-melanocyte-stimulating hormone and regulation by leptin

“…It is known that fasting, which is a state of low serum leptin levels, results in reduced amounts of POMC mRNA levels. This reduction is also seen in the hypothalamus of the leptin-deficient ob͞ob mice (13)(14)(15)(16). In addition, hypothalamic POMC mRNA is stimulated by the administration of recombinant leptin to rodents (16).…”

Caloric restriction: Impact upon pituitary function and reproduction

“…POMC can be differentially cleaved by proteases to generate an array of hormones (adrenocorticotrophic hormone [ACTH], lipotropin, corticotrophin-like intermediate peptide [CLIP], melanocyte-stimulating hormone [MSH] and β-endorphin) that exert multiple effects crucial in linking the organism's metabolic state to its reproductive capacity. The expression of POMC mRNA is significantly reduced by CR implemented upon rats, mice and also primates (Bergendahl et al, 1992;Koegler et al, 2001;Schwartz et al, 1997;Mizuno et al, 1998). The proteolytic cleavage products themselves of POMC have differential effects on the reproductive axis, e.g.…”

Reproductive ecology and life history of the human male

“…Neither GnRH producing cells nor mRNA levels were altered in rat hypothalami after severe food restriction, although the role of endogenous opioids such as proopiomelanocortin (POMC) in suppressing GnRH production was not ruled out (Bergendahl et al, 1992). Alternatively, declines in GnRH receptor gene transcription rates within the pituitary may be compromised in association with food restriction (Gruenewald and Matsumoto, 1993).…”