Gonadotropin-Releasing Hormone-II Messenger Ribonucleic Acid and Protein Content in the Mammalian Brain Are Modulated by Food Intake

Abstract

GnRH-II is the most evolutionarily conserved member of the GnRH peptide family. In mammals, GnRH-II has been shown to regulate reproductive and feeding behaviors. In female musk shrews, GnRH-II treatment increases mating behaviors and decreases food intake. Although GnRH-II-containing neurons are known to reside in the midbrain, the neural sites of GnRH-II action are undetermined, as is the degree to which GnRH-II is regulated by energy availability. To determine whether GnRH-II function is affected by changes in food intake, we analyzed the levels of GnRH-II mRNA in the midbrain and GnRH-II protein in numerous target regions. Adult musk shrews were ad libitum fed, food restricted, or food restricted and refed for varying durations. Compared with ad libitum levels, food restriction decreased, and 90 min of refeeding reinstated, GnRH-II mRNA levels in midbrain and GnRH-II peptide in several target areas including the medial habenula and ventromedial nucleus. Refeeding for 90 min also reinstated female sexual behavior in underfed shrews. In male shrews, abundant GnRH-II peptide was present in all sites assayed, including the preoptic area, a region with only low GnRH-II in females. In contrast to females, food restriction did not affect GnRH-II protein in male brains or inhibit their mating behavior. Our results further define the relationship between GnRH-II, energy balance, and reproduction, and suggest that food restriction may inhibit female reproduction by reducing GnRH-II output to several brain nuclei. We postulate that this highly conserved neuropeptide functions similarly in other mammals, including humans, to fine-tune reproductive efforts with periods of sufficient energy resources.

Caloric restriction: Impact upon pituitary function and reproduction

“…decline of circulating LH and testosterone, however can be reversed rapidly upon feeding, suggesting that there is a calorie-dependent regulation of GnRH pulse-generator output (Aloi et al, 1997). Further linking GnRH function, there is evidence of not only GnRHs role in generic neuronal excitability during fasting (Röjdmark, 1987), controlling the desire behind food intake (Kauffman et al, 2005a), but there is also evidence that food intake itself directly controls the mRNA and protein levels of GnRH in mammalian brains (Kauffman et al, 2006). It has been shown that even short periods of dietary energy deprivation (24-72 h) can have dramatic effects upon the hypothalamic-pituitary-gonadal (HPG) axis in humans and animal models.…”

Neuropeptide Y influences acute food intake and energy status affects NPY immunoreactivity in the female musk shrew (Suncus murinus)

“…The third GnRH II-related area we examined, the mHB, was non-responsive to food condition and this region also has little or no NPY-ir in the rat (de Quidt and Emson, 1986). GnRH II mRNA and peptide content are likewise affected by energy status, both decrease after 2 days of food restriction (the same feeding paradigm used here) and GnRH II mRNA was reversed by 90 minutes of ad libitum access to food (Kauffman, Bojkowska, Wills, and Rissman, 2006). GnRH II content in the PAG showed the inverse response to restriction and refeeding as compared with NPY-ir; GnRH II peptide levels dropped in restricted females and increased after 180 minutes (but not sooner) of food intake.…”

“…In musk shrews, both GnRH I and GnRH II fibers are present in the hypothalamus. Protein and mRNA levels of both peptides are affected by food intake (Kauffman et al, 2006;Temple and Rissman, 2000a). The amount of GnRH I peptide in the median eminence is reduced by food restriction and this affects ovulation (Temple and Rissman, 2000a), and GnRH II reduces food intake and is permissive for reproduction (Temple et al, 2003).…”

Contribution of Chicken GnRH-II and Lamprey GnRH-III on Gonadotropin Secretion

“…Nevertheless, ICV infusion of cGnRH-II but not mGnRH stimulated sexual behavior in nutritionally challenged female musk shrews (Temple et al, 2003). When musk shrews were exposed to different levels of caloric intake, cGnRH-II mRNA expression was modulated by feed intake (Kauffman et al, 2006;Kauffman and Rissman, 2004b). These data suggest a role of GnRH-II in both feeding and sexual behavior.…”