Searching for Neural Correlates of Sexual Differentiation in a Heterogeneous Tissue

Abstract

Nearly 20 years have passed since the hypothalamus-preoptic area (HPOA) was identified as a target tissue mediating the effects of gonadal steroids on male and female sexual behaviour (Davidson and Bloch 1969; Eisenfeld and Axelrod 1965; Lisk 1962, 1967; Harris and Michael 1964). Since then our knowledge of how HPOA cells accumulate and metabolize steroids has rapidly progressed. We know, for example, that HPOA cells that respond to testosterone (T) often convert it first to oestradiol (OE₂) and/or di- hydrotestosterone (DHT; Luttge 1979, Martini 1982). These metabolites then bind to intracellular receptors. In this regard, T-sensitive cells in the HPOA resemble T-sensitive cells in the male reproductive tract. In females, HPOA cells that respond to progesterone (P) resemble P-sensitive cells in the female reproductive tract in that they synthesize most of their P receptors only after they have been exposed to OE₂ (Blaustein and Brown, this Vol.; Moguilewski and Raynaud 1979a,b; MacLusky and McEwen 1978, 1980). The receptors themselves are similar in the HPOA and peripheral targets (Barley et al. 1975; Feder et al. 1979; Moguilewsky and Raynaud 1979a), and in both tissues, the steroid eventually binds to acceptor sites on the chromatin (Fox and Johnston 1974; Whalen and Olsen 1978). Moreover, these processes are similar in adults and neonates (MacLusky and Naftolin 1981). These observations have encouraged the view that steroids activate mating behaviour in adulthood, and sexually differentiate the HPOA during early development, in the same way that they modify cellular functions in other parts of the body, i.e., by modifying synthesis of messenger RNA and protein.