Mechanisms underlying estrogen-induced sexual differentiation in the hypothalamus.

Estrogen plays critical roles in the sexual differentiation of the developing brain and gender-specific regulation of reproductive neuroendocrinology. Of the different regions of the brain, it is well known that hypothalamic areas contain key sexually differentiated neuronal circuits. Estrogen receptor (ER) proteins localized in the nucleus affect the expression of target genes when bound to their ligand estrogen. However, recent studies suggest that this may not be the only mechanism of estrogen action. Instead, estrogen can influence various cellular events through regulating different signaling pathways. Cross-talk between direct effects of estrogen on gene transcription and its effects on signaling pathways should be examined in future to elucidate mechanisms underlying sexual differentiation in the hypothalamus.