Aromatase and intracrinology of estrogen in hormone-dependent tumors.

Aromatase (estrogen synthetase) has been shown to occur in various extragonadal tissues as well as gonadal tissues, to be tissue-specifically regulated by various factors, and to play important roles in physiological functions in various tissues. The human gene is revealed to contain multiple variants of exon 1 which are tissue-specifically selected. Each exon 1 is flanked with a unique promoter region, which may explain tissue-specific transcription. All results strongly support an idea of intracrinology of estrogen. The validity of this concept is verified in connection with plasma levels of various steroid hormones and association constants of aromatase and estrogen receptor. 17beta-Estradiol is locally produced through several metabolic pathways. In this context, aromatase, steroid sulfatase, estrogen sulfotransferase, and 17beta-hydroxysteroid dehydrogenases I and II are considered to be important factors in the development of hormone-dependent tumors.