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Sex hormones have developmental trophic actions on neurons and glial cells and activational effects in the adult brain. It has been proposed that sex steroids may interact with peptide trophic factors to induce part of their biological effects in the nervous system. The first evidence of such an interaction was provided by Toran-Allerand et al (Brain Research 1980; 184: 517-524), showing that in explant cultures of fetal rodent hypothalamus, estrogen and insulin have synergistic effects on neurite growth, an effect probably mediated by insulin-like growth factor-1 receptors. Recent data indicate that estrogen and insulin-like growth factor-1 signaling pathways interact on hypothalamic neurons to regulate survival and differentiation and that sex steroids interact with a variety of different trophic signals in vivo to regulate neuroendocrine events. These findings suggest that trophic factors may be involved in the genesis of sex differences in the developing brain and in the maintenance of a sexually differentiated brain function in the adult. Biomedical Reviews 1997; 7: 67-74.

Interaction of gonadal steroids and growth factors in brain sex differentiation