Regulation of oestrogen action: role of 17 beta-hydroxysteroid dehydrogenases.

The target cell responses to steroid hormones, such as oestrogens, are dependent on the expression of their receptors. Apart from receptor concentration, another key regulatory factor in steroid hormone action is the intracellular hormone concentration, which is affected by three main variables: the concentration of the steroid in plasma, local production and local conversion into metabolites. During the reproductive years the main source of oestrogens is the ovarian follicle, but in postmenopausal women most of the oestrogens are formed in peripheral tissues. The present overview deals with the formation of active oestrogens in steroidogenic tissues and in oestrogen target tissues, and the main focus is on 17 beta-hydroxysteroid dehydrogenases, which catalyse the interconversion between oestradiol and oestrone. It is evident that different 17 beta-hydroxysteroid dehydrogenase isoenzymes are responsible for the oxidation/reduction of oestradiol or oestrone in oestrogen target cells. Because these enzymes are involved in the biosynthesis and metabolism of oestrogens, they have an important physiological significance for the growth of oestrogen-dependent tissues and, hence, the growth and progression of hormone-dependent tumours.