Estrogen biosynthesis and receptors

Most of the enzymes involved in steroidogenesis belong to the family of cyt ochrome P450. Most of the corresponding genes have been cloned. The key enz yme for estradiol biosynthesis is P 450 arom. Several germline mutations ha ve been described. These observations have lead to reconsider the role of e stradiol. Estradiol plays a key role in bone growth and mineralisation and in gonadotrope regulation in male. Moreover, the recent discovery that an additional estrogen receptor (ERP) i s present in various tissues has advanced ou, understanding of the mechanis ms underlying estrogen signalling. It suggests the existence of two previou sly unrecognized pathways of estrogen signalling : via the ERP sub type in tissues exclusively expressing this subtype and via the formation of hetero dimers in tissues expressing both ER subtypes. Various models have been sug gested as explanations for the stricking cell and promoter-specific effects of estrogens and antiestrogens, all on the basis of the assumption that on ly a single ER exists. These models have to be reconsidered Moreover, new a ntiestrogens with improved therapeutic profils could be designed.