期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 171, 期 1-2, 页码 21-24出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0303-7207(00)00429-9
关键词
progesterone; mineralocorticoid receptor; progesterone metabolism
Progesterone (P) is a mineralocorticoid (MC)-antagonist in vitro. During pregnancy, plasma P concentrations exceed aldosterone concentrations at least 50-fold, but plasma aldosterone increases only 4 8-fold in a compensatory manner. Since the in vivo anti-MC activity of P seems to be only moderate, we hypothesized that P is metabolized by enzymes of MC target tissue similar to the way cortisol is metabolized by 11 beta -hydroxysteroid dehydrogenase (11 beta -HSD) type 2 in order to protect the MC receptor. We, therefore. examined P metabolism using 4-C-14-P in subcellular fractions of human postmenopausal and male kidneys, and in homogenates of one premenopausal kidney. We found that P is converted effectively. even at high P concentrations (10(-6) mol/l), to various metabolites: 20 alpha -dihydro(DH)-P: 17 alpha -OH-P: 17 alpha -OH,20 alpha -DH-P: 5 alpha -DH-P: 3 beta .5 alpha -tetrahydro(TH)-P: and 20 alpha -DH,5 alpha -DH-P. Homogenates of premenopausal kidney also showed conversion to 3 alpha- and 5 beta -reduced P metabolites. These results confirm the existence of an efficient renal enzyme system as a possible mechanism of an enzyme-mediated MC receptor selectivity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
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