Abstract
There is general agreement that the central nervous system in rodents differs between sexes due to the presence of gonadal steroid hormone during differentiation. Sex differences in feeding seem to occur among species, and responses to fasting (i.e., starvation), gonadal steroids (i.e., testosterone and estradiol), and diet (i.e., western-style diet) vary significantly between sexes. The hypothalamus is the center for controlling feeding behavior. We examined the activation of feeding-related peptides in neurons in the hypothalamus. Phosphorylation of cyclic AMP response element-binding protein (CREB) is a good marker for neural activation, as is the Fos antigen. Therefore, we predicted that sex differences in the activity of melanin-concentrating hormone (MCH) neurons would be associated with feeding behavior. We determined the response of MCH neurons to glucose in the lateral hypothalamic area (LHA) and our results suggested MCH neurons play an important role in sex differences in feeding behavior. In addition, fasting increased the number of orexin neurons harboring phosphorylated CREB in female rats (regardless of the estrous day), but not male rats. Glucose injection decreased the number of these neurons with phosphorylated CREB in fasted female rats. Finally, under normal spontaneous food intake, MCH neurons, but not orexin neurons, expressed phosphorylated CREB. These sex differences in response to fasting and glucose, as well as under normal conditions, suggest a vulnerability to metabolic challenges in females.
Highlights
There is general agreement that the central nervous system in rodents differs between sexes due to the presence of gonadal steroid hormone during differentiation (Phoenix et al, 1959; Gorski and Barraclough, 1963)
The apparent difference in sexual differentiation between primates and rodents may be due to differences between the hypothalamus- and pituitary-mediated control of gonadotropin secretion, since Fos is not expressed in response to gonadotropin-releasing hormone in monkeys (Witkin et al, 1994) but its expression is essential in rodents (Hoffman et al, 1990; Lee et al, 1990b,a)
We predicted that sex differences in the activity of melanin-concentrating hormone (MCH) neurons would be associated with feeding behavior
Summary
There is general agreement that the central nervous system in rodents differs between sexes due to the presence of gonadal steroid hormone during differentiation (Phoenix et al, 1959; Gorski and Barraclough, 1963). The organizing action of prenatally administered testosterone is evident on tissues that mediate mating behavior in female rodents (Arnold and Gorski, 1984). Sexual differentiation of the brain is more complicated (McCarthy, 2008; Schwarz and McCarthy, 2008a; Nugent and McCarthy, 2011; Wu and Shah, 2011; Lenz et al, 2013) than once thought, even in rodents
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