Target-dependent sexual differentiation of a limbic-hypothalamic neural pathway

Neural pathways between sexually dimorphic forebrain regions develop under the influence of sex steroid hormones during the perinatal period, but how these hormones specify precise sex-specific patterns of connectivity is unknown. A heterochronic coculture system was used to demonstrate that sex steroid hormones direct development of a sexually dimorphic limbic-hypothalamic neural pathway through a target-dependent mechanism. Explants of the principal nucleus of the bed nuclei of the stria terminalis (BSTp) extend neurites toward explants of the anteroventral periventricular nucleus (AVPV) derived from male but not female rats. Coculture of BSTp explants from male rats with AVPV explants derived from females treated in vivo with testosterone for 9 d resulted in a high density of neurites extending from the BSTp to the AVPV explant, as was the case when the BSTp explants were derived from females and the AVPV explants were derived from males or androgen-treated females. These in vitro findings suggest that during the postnatal period testosterone induces a target-derived, diffusible chemotropic activity that results in a sexually dimorphic pattern of connectivity.