The orexigenic effect of melanin-concentrating hormone (MCH) is influenced by sex and stage of the estrous cycle

Abstract

Recently, it was shown that that the orexigenic effect of melanin concentrating hormone (MCH) is attenuated by estradiol treatment in ovariectomized (OVX) rats. This suggests that female rats may be less responsive than male rats to the behavioral effects of MCH. To investigate this hypothesis, the effects of lateral ventricular infusions of MCH on food intake, water intake, meal patterns, and running wheel activity were examined in male and female rats. To further characterize the impact of estradiol on MCH-induced food intake, female rats were OVX and tested with and without 17-β-estradiol benzoate (EB) replacement. In support of our hypothesis, food and water intakes following MCH treatment were greater in male rats, relative to female rats. Specifically, the orexigenic effect of MCH was maximal in male rats and minimal in EB-treated OVX rats. In both sexes, the orexigenic effect of MCH was mediated by a selective increase in meal size, which was attenuated in EB-treated OVX rats. MCH induced a short-term (2 h) decrease in wheel running that, unlike its effects on ingestive behavior, was similar in males and females. Thus, estradiol decreases some, but not all, of the behavioral effects of MCH. To examine the influence of endogenous estradiol, food intake was monitored following MCH treatment in ovarian-intact, cycling rats. As predicted by our findings in OVX rats, the orexigenic effect of MCH was attenuated in estrous rats, relative to diestrous rats. We conclude that the female rat's reduced sensitivity to the orexigenic effect of MCH may contribute to sex-and estrous cycle-related differences in food intake.

Chemical identity and connections of medial preoptic area neurons expressing melanin-concentrating hormone during lactation

“…Intracerebroventricular administration of MCH increases feeding (Qu et al, 1996;Rossi et al, 1997;Gomori et al, 2003;Santollo and Eckel, 2008). Mice deficient in MCH are hypophagic and lean and show reduced adipose tissue mass and increased energy expenditure (Shimada et al, 1998).…”

The roles of melanin-concentrating hormone in energy balance and reproductive function: are they connected?

“…Messina et al (2006) found that oestradiol treatment decreased MCH-induced food intake. Santollo & Eckel (2008) also reported that both exogenous oestradiol and endogenous oestradiol exert a reductive effect on MCH-induced feeding via decreased meal size. Furthermore, a difference in the magnitude of the orexigenic effects of MCH between different stages of the oestrous cycle was observed, with these effects being attenuated in oestrous rats (following high oestradiol secretion) compared with dioestrous rats.…”

“…Furthermore, in some studies, elevated energy expenditure was observed in males only , Alon & Friedman 2006. In one study, locomotor activity was decreased following MCH administration (Santollo & Eckel 2008). Interestingly, increased energy expenditure resulting from the decreased availability of physiological hypothalamic MCH may be accompanied by either hyperphagia or hypophagia.…”

“…Hyperphagia or hypophagia can be induced by manipulating the availability of physiological hypothalamic MCH concentrations. While increased availability results in hyperphagia (Ludwig et al 2001, Gomori et al 2003, Santollo & Eckel 2008, decreased availability can result in either hyperphagia , Marsh et al 2002 or hypophagia (Mashiko et al 2005, Kowalski et al 2006. This discrepancy may be attributed to the use of either a genetic or pharmacological rodent model.…”

“…Therefore, an important distinction appears to be that in pharmacological models altered feeding behaviours are largely responsible for the resultant phenotype, while in genetic models altered energy expenditure accounts for changes in phenotype as feeding behaviours may remain unaltered, increased or decreased (Pissios 2009; Table 1). MCH treatment also seems to be able to affect meal size, which is increased following the administration of MCH (Santollo & Eckel 2008) or decreased following the antagonism of the MCH receptor (Kowalski et al 2006).…”