Endogenous opioid-immunoreactive neurons of the ventromedial hypothalamic nucleus concentrate estrogen in male and female rats

Estrogen stimulates expression of proenkephalin mRNA in neurons of the hypothalamic ventromedial nucleus, and evidence is accumulating that synaptic release of one of the peptide end products, met‐en‐kephalin, influences events that regulate reproductive behavior. To address the question of whether estrogen acts directly on neurons that synthesize met‐en‐kephalin or indirectly through a separate neuronal population, we combined estrogen autoradiography with endogenous opioid peptide (EOP) immunohistochemistry. In agreement with previous studies, the ventrolateral subdivision of the hypothalamic ventromedial nucleus was densely packed with EOP‐immunoreactive cells. In males, 48% of the estrogen‐concentrating cells of the ventrolateral subdivision of the hypothalamic ventromedial nucleus contained EOP, and, in females, 27% of the estrogen‐concentrating cells contained EOP. These findings indicate that estrogen acts directly on neurons that express EOP and suggest a mechanism that underlies sexually differentiated reproductive behavior.