20alpha-hydroxysteroid dehydrogenase (20αHSD) has been initially characterized as a progesterone metabolizing enzyme of the ovary mandatory for the final reduction of progesterone blood levels before parturition. As the exact zonal distribution and regulation of adrenal 20αHSD has not been defined, adrenal 20αHSD expression and activity was determined by western blotting, immunohistochemistry and enzymatic assays in wild type BALB/c mice of both genders at different time points and following various hormonal treatments. In addition, to explore possible direct effects of 20αHSD expression on adrenal function, mice with targeted deletion of 20αHSD were studied for effects on adrenal morphology. Age related enzymatic activity and protein expression showed a clear gender difference with peak activity in males at 3 weeks and loss of activity thereafter but retained activity in virgin female mice. Interestingly, this time course of adrenal 20αHSD enzymatic activity is reminiscent of the growth kinetics of the adrenal X-zone. In fact, immunohistochemical staining confirmed X-zone restricted expression of 20αHSD. Accordingly, induction of X-zone regression in female mice by first pregnancy or testosterone treatment was accompanied by a rapid drop of adrenal 20αHSD expression and activity. In contrast, induction of pseudo-pregnancy did not affect adrenal 20αHSD enzyme activity. Moreover, gonadectomy in post-pubertal male mice which is known to induce growth of a secondary X-zone results in the restoration of adrenal 20αHSD enzyme activity. Adrenal glands from 20αHSD knock out animals at various time points displayed normal timing of X-zone growth and regression. Taking together, these findings indicate that regulation of 20αHSD activity differs between the ovary and the adrenal cortex. Moreover, although adrenal 20αHSD expression is restricted to the X-zone, adrenal 20αHSD expression is not required for X-zone proliferation and regression. Ongoing in vitro experiments aim at the further elucidation of factors involved in 20αHSD regulation through promoter activation vs. regulation through growth and apoptosis of 20αHSD expressing X-zone cells.
01 - 05 Apr 2006
European Society of Endocrinology