REGULATION OF SEX-SPECIFIC FORMATION OF ESTROGEN IN BRAIN-DEVELOPMENT- ENDOGENOUS INHIBITORS OF AROMATASE

Brain sexual differentiation occurs during steroid-sensitive phases in early development, and is affected particularly by exposure to oestro gens formed in the brain by aromatisation of androgen. The organisatio nal effects of oestrogen result in male-specific neuronal morphology, control of reproductive behaviour, and patterns of gonadotrophin secre tion. A question which still has to be resolved is what determines cha nges in aromatase activity effective for the differentiation of sexual ly dimorphic brain development during sensitive periods of growth. In the mouse, a sex difference exists at early stages of embryonic develo pment in aromatase-containing neurones of the hypothalamus. The embryo nic aromatase system is regulated later in foetal development by andro gens. Testosterone treatment increases the numbers of aromatase-immuno reactive hypothalamic neuronal cell bodies. Kinetic evidence from stud ies on the avian brain suggest that endogenous steroid inhibitors of a romatase, probably formed within neuroglia, also have a role in the co ntrol of oestrogen production. Inhibitory kinetic constant determinati on of endogenous androgenic metabolites formed in the brain showed tha t preoptic aromatase is potently inhibited by 5 alpha-androstanedione (K-i = 6 nM) and less strongly by 5 beta-dihydrotestosterone (K-i = 35 0 nM). Regulation by steroidal and possibly non-steroidal inhibitors m ay contribute to the special characteristics and plasticity in aromata se activity which develops at certain stages in ontogeny.