Androgen receptors exist throughout the ‘critical period’ of brain sexual differentiation

Abstract

Several studies suggest direct roles for androgens and oestrogens in the development of sexually dimorphic characteristics of mouse and rat brain¹. To elucidate the biochemical mechanisms for such effects, investigators have asked which putative steroid receptors are present in the hypothalamus throughout the critical period of sexual differentiation. A priori, potential receptors would include high-affinity proteins with selectivities for active androgens, oestrogens and their metabolites. Two major classes of steroid that might be active as agonists are the androgens per se, including testosterone and dihydrotestosterone (DHT)², and the oestrogens, which are themselves androgen metabolites³. Normally, in sexual differentiation, a proper balance of both androgens and oestrogens may be necessary⁴. Indeed, receptors for each of these ligands do exist in the hypothalamus of neonatal and prepubertal mice^4–7. Although the perinatal oestrogen receptor and its function have been extensively studied^7,8, the existence of perinatal androgen receptors has not been as clearly demonstrated to permit a similar acceptance⁹. In this report, we establish the existence of adult-like androgen receptors in embryonic and neonatal mouse and rat hypothalami by qualitative biochemical and genetic analyses. This is achieved by DNA–cellulose affinity chromatography and velocity sedimentation, and by analysis of the androgen-resistant mutant, testicular feminisation. The presence of sex hormone receptors in perinatal brain is discussed in the context of behavioural responses which are differentiated during the critical period of brain sexual development.