Role of testosterone in the activation of sexual behavior and neuronal circuitries in the senescent brain.

Several studies performed in mammals and, more recently, in other vertebrates, demonstrated that sex differences in reproductive behavior as well as in neuronal circuitries involved in its control largely depend on steroid hormones. The perinatal exposure to gonadal steroids and the presence of the appropriate gonadal hormones in the adulthood are necessary for the full expression of sexual behaviour (for a complete list of references see Panzica et al., 1995). More recently, a new group of studies indicated that gonadal hormones can cause changes in brain morphology and functions in the adult brain also in regions which are not directly related to sexual functions (i.e. the regulation of cholinergic neurons by estradiol in the rat forebrain according to a sexually dimorphic pattern). Furthermore, other steroid hormones either than gonadal hormones are also effective on neural structures which do not belong to the traditional neuroendocrine brain targets (Luine and Harding, 1994). With aging, the gonads undergo anatomical, histological and vascular changes, and as a result of these changes all forms of circulating gonadal hormones decrease in both female and male. The magnitude of this decline is considerably dependent on individuals, age and health status (for a review see Timiras et al., 1995). As a consequence, alterations that occur in neuroendocrine systems during aging can provide new insights into the general problem of how steroid modulate neuronal circuitries throughout the life. The localization of gonadal steroid hormone sensitive regions in the brain has been accomplished in many vertebrate species. These studies established that receptor sites for estrogens, androgens, progestins, glucocorticoids, and mineralcorticoids exist in a phylogenetically stable manner in various regions of the brain (McEwen et al., 1979). The immunocytochemical detection of steroid receptors at neuronal level of resolution gave strenght to the hypothesis that a specific action of these hormones in the differentiation and in the postnatal development of target cerebral circuits did occur. Indeed receptors for gonadal steroids and dimorphic structures were frequently observed in the same or in closely related regions, providing indirect evidence that the origin and the presence of these neuroanatomical dimorphisms might be determined by the action of gonadal steroids (for a list of reference see Kawata, 1995). A more convincing demonstration of the significance of gonadal hormones in the regulation of sexual dimorphisms has been recently provided by the administration of antisense oligoprobes to estrogen receptor (ER). When these antisense oligoprobes were administered during a sensitive developmental period they prevent the establishment of the sexual dimorphism in the rat preoptic region (McCarthy et al., 1993).