Pomc mRNA was regulated by various estrogen receptors in a sex-specific manner. (a) ESR1 selective agonist PPT and (b) ESR2 selective agonist DPN did not affect Pomc mRNA. (c) PPT and DPN showed decreased Pomc mRNA in females. (d) Membrane estrogen signaling agonist, estrogen dendrimer conjugate (ED), showed no regulation of Pomc mRNA. (e) PPT plus DPN plus ED decreased Pomc mRNA in females. (f) Finally, the GPER agonist, G1, decreased Pomc mRNA in males. PPT males, n = 11; PPT females, n = 9 to 10; DPN males, n = 9 to 10; DPN females, n = 8; PPT plus DPN males, n = 11; PPT plus DPN females, n = 8 to 10; ED males, n = 10; ED females, n = 9; PPT plus DPN plus ED males, n = 7 to 13; PPT plus DPN plus ED females, n = 9 to 12; G1 males, n = 9 to 10; G1 females, n = 6 to 10. #P ≤ 0.05.