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Pure Appl. Chem., 2003, Vol. 75, No. 11-12, pp. 1771-1784

Nuclear receptor action involved with sex differentiation

I. A. Hughes, Howard Martin, Jarmo Jääskeläinen and C. L. Acerini

Department of Paediatrics, University of Cambridge, Addenbrooke ’s Hospital, Box 116, Cambridge CB2 2QQ, UK

Abstract: Sex determination and differentiation in the male is an orderly sequence of events coordinated by genetic and hormonal factors operating in a time- and concentration-dependent manner. The constitutive sex in mammals is female. Disorders of fetal sex development have provided the means to identify testis-determining genes and the molecular mechanisms of hormone action. Thus, the androgen receptor, a nuclear hormone receptor critical for androgen-induced male sex differentiation, displays unique intra-receptor and protein-protein interactions which, when disturbed, can result in extreme forms of sex reversal. Polymorphic variants are associated with milder disorders of sex development. Against this genetic background, endocrine active substances may further contribute to the underlying causes of an increase in male reproductive tract disorders.