Estradiol induced inhibition of 11beta-hydroxysteroid dehydrogenase 1: an explanation for the postmenopausal hormone replacement therapy effects.
The adverse and beneficial effects of postmenopausal hormone replacement therapy include: ischemic heart disease, stroke, pulmonary embolism, breast cancer, an increased rate of onset of asthma as well as reductions in the incidence of diabetes in women with known coronary artery disease and osteoporotic fractures. These varied effects can be explained by the down regulation of 11beta-hydroxysteroid dehydrogenase by estradiol, which results in a reduction of tissue specific cortisol production. The reduction in local cortisol production which diminishes the endogenous anti-inflammatory effects, also allows for the progression of both vascular and pulmonary inflammation. The decrease in cortisol activation reduces insulin resistance and anti-proliferative effects thereby reducing the potential for diabetes but allowing for the emergence of malignancy. Furthermore, the decreased local tissue availability of cortisol reduces the tendency for the development of osteoporosis. New techniques and drugs are being developed to evaluate the modulation of 11beta-HSD1 activity. Further study should result in new ways to control both inflammation and metabolism.
Cohen
Paul G
PG
Department of Pharmaceutical Sciences, Southern School of Pharmacy, Mercer University, P.O. Box 191405, Atlanta, GA 31119, USA. cohenpg@bellsouth.net
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy
D004791:Enzyme Inhibitors; D004958:Estradiol; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1