ROLE OF ASTROGLIA AND INSULIN-LIKE GROWTH-FACTOR-I IN GONADAL HORMONE-DEPENDENT SYNAPTIC PLASTICITY

Gonadal hormones exert a critical influence over the architecture of s pecific brain areas affecting the formation of neuronal contacts. Cell ular mechanisms mediating gonadal hormone actions on synapses have bee n studied extensively in the rat arcuate nucleus, a hypothalamic cente r involved in the feed-back regulation of gonadotropins. Gonadal stero ids exert organizational and activational effects on arcuate nucleus s ynaptic connectivity. Perinatal testosterone induces a sexual dimorphi c pattern of synaptic contacts. Furthermore, during the preovulatory a nd ovulatory phases of the estrous cycle there is a transient disconne ction of inhibitory synaptic inputs to the somas of arcuate neurons. T his synaptic remodeling is induced by estradiol, blocked by progestero ne, and begins with the onset of puberty in females. Astroglia appear to play a significant role in the organizational and the activational hormone effects on neuronal connectivity by regulating the amount of n euronal membrane available for the formation of synaptic contacts and by releasing soluble factors, such as insulin-like growth factor I (IG F-I), which promote the differentiation of neural processes. Recent ev idence indicates that gonadal steroids and IGF-I may interact in their trophic effects on the neuroendocrine hypothalamus. Estradiol and IGF -I promote the survival and morphological differentiation of rat hypot halamic neurons in primary cultures. The effect of estradiol depends o n IGF-I, while the effects of both estradiol and IGF-I depend on estro gen receptors. Furthermore, estrogen activation of astroglia in hypoth alamic tissue fragments depends on IGF-I receptors. These findings ind icate that IGF-I may mediate some of the developmental and activationa l effects of gonadal steroids on the brain and suggest that IGF-I may activate the estrogen receptor to induce its neurotrophic effects on h ypothalamic cells. In addition, IGF-I levels in the neuroendocrine hyp othalamus are regulated by gonadal steroids. IGF-I levels in tanycytes , a specific astroglia cell type present in the arcuate nucleus and me dian eminence, increase at puberty, are affected by neonatal androgen levels, show sex differences, and fluctuate in accordance to the natur al variations in plasma levels of ovarian steroids that are associated with the estrous cycle. These changes appear to be mediated by hormon al regulation of IGF-I uptake from blood or cerebrospinal fluid by tan ycytes. These results suggest that tanycytes may be involved in the re gulation of neuroendocrine events in adult rats by regulating the avai lability of IGF-I to hypothalamic neurons. In summary, IGF-I and diffe rent forms of neuron-astroglia communication are involved in the effec ts of estradiol on synaptic plasticity in the hypothalamic arcuate nuc leus. (C) 1997 Elsevier Science Inc.