Immunohistochemical assessment of the effect of gonadal steroid hormones on the food intake suppressive function of nesfatin neurons

Gonadal hormones especially estrogens play a key role in metabolism and energy homeostasis. It's known that estrogens decrease food intake. Estrogens show their effects via binding to their receptors. Estrogen receptor alpha and beta (ER-⍺ ve ER-β) are nuclear receptors which expressed in varied brain areas associated with body weight and food intake control, including the hypothalamus. Nesfatin-1 is an anorexigenic peptide which regulate homeostatic feeding. In the brain nesfatin-1 expressing neurons perform their actions mainly in the hypothalamus. In the literature, there is no study showing the relationship between estrogen and nesfatin-1 neurons. In this study, we aimed to investigate whether central anorexigenic effect of nesfatin-1 through estrogen by directly ER-⍺ and/or ER-β which expressed in nesfatin-1 neurons or not and any possible gender difference in this expression. For this aim, nesfatin-1 and ER-⍺ or ER-β co-localization was investigated in the hypothalamic neurons by using dual-immunohistochemical technique on free-floating, brain sections. In this study, adult Sprague-Dawley rats were used. The ratio of ER-⍺ and ER-β positive nesfatin-1 neurons to all nesfatin-1 neurons was calculated. In arcuate nucleus the percentage of nesfatin-1 neurons expressing ER-⍺ was 29% in female rats and 40% in male rats. The percentage of ER-⍺ expression in male rats was higher and it was found statistically significant, too. ER-⍺ immunoreactivity in nesfatin-1 neurons was determined as 27% in female and male rats in periventricular nucleus and there wasn't a significant difference between two groups. The percentage of nesfatin-1 neurons expressing ER-β was determined in paraventricular nucleus and it was 63% in female rats and 58% in male rats and as a result of statistical analyses there wasn't any significant difference between genders. As a result co-localization of ER-⍺ and ER-β in nesfatin-1 neurons is detected for the first time with this study. And it is suggested that estrogens may mediate activity of nesfatin-1 neurons through ER-⍺ and ER-β. Key Words: Food intake, Nesfatin-1, Estrogen, Estrogen receptor alpha, Estrogen receptor beta