Melanin concentrating hormone and estrogen receptor-α are coexstensive but not coexpressed in cells of male rat hypothalamus

In male rats, estradiol (E2) exerts marked anorectic effects. One mechanism proposed for this effect is an E2-mediated down-regulation of the orexigenic neuropeptide melanin concentrating hormone (MCH). Previous anatomical work has shown that both MCH and estrogen receptor α (ERα) are found in quantity in the lateral hypothalamic area (LHA), a structure long associated with appetite and ingestive behavior. It has been hypothesized that the most direct manner by which E2 could affect MCH expression and feeding would be via classical nuclear ERα located in MCH neurons. To evaluate this notion, we performed double-label immunohistochemistry for MCH and ERα in male rat hypothalamus. We report here that MCH neurons do not contain ERα, suggesting that the primary locus for estrogenic control of feeding is not the MCH neurons themselves. Rather, we show substantial overlap in the anatomical distribution of both cell types, raising the possibility that E2 influences MCH signaling indirectly via adjacent ERα-containing cells.