INTERACTION OF THE SIGNALING PATHWAYS OF INSULIN-LIKE GROWTH-FACTOR-IAND SEX STEROIDS IN THE NEUROENDOCRINE HYPOTHALAMUS

Among the numerous endocrine signals that affect the central nervous s ystem, sex steroids play an important role. It has been recently postu lated that part of the effects of these hormones on the brain may be m ediated by trophic factors, such as insulin-like growth factor I (IGF- I). Both estradiol and IGF-I increase the survival and differentiation of developing fetal rat hypothalamic neurons in culture. The effect o f estradiol is blocked by the pure estrogen receptor antagonist ICI 18 2,780, by an antisense oligonucleotide to the estrogen receptor, and b y an antisense oligonucleotide to IGF-I. In rum, the effect of IGF-I i s blocked by ICI 182,780 and by the antisense oligonucleotide to the e strogen receptor. These findings indicate that estrogen-induced activa tion of the estrogen receptor in developing hypothalamic neurons requi res the presence of IGF-I and that both estradiol and IGF-I use the es trogen receptor to mediate their trophic effects on hypothalamic cells . In vivo, sex steroids affect IGF-I levels in the endocrine hypothala mus. ICF-I levels in tanycytes, a specific subtype of glial cells pres ent in the arcuate nucleus and median eminence, are sexually dimorphic in the rat, increase with the onset of puberty, and are regulated by perinatal and adult levels of sex steroids. These changes may be due t o hormonal modifications of IGF-I uptake by tanycytes from blood or ce rebrospinal fluid. Therefore, this type of glial cell appears to play a central role in the interaction of sex steroids and IGF-I in the hyp othalamus.