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

In male rats, estradiol (E(2)) exerts marked anorectic effects. One mechanism proposed for this effect is an E(2)-mediated down-regulation of the orexigenic neuropeptide melanin concentrating hormone (MCH). Previous anatomical work has shown that both MCH and estrogen receptor alpha (ERalpha) 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 E(2) could affect MCH expression and feeding would be via classical nuclear ERalpha located in MCH neurons. To evaluate this notion, we performed double-label immunohistochemistry for MCH and ERalpha in male rat hypothalamus. We report here that MCH neurons do not contain ERalpha, 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 E(2) influences MCH signaling indirectly via adjacent ERalpha-containing cells.