Abstract
The (+)- and (-)-gossypols potently inhibit human and rat 11ß-hydroxysteroid dehydrogenase type 2
Chen,Bing-Bing; Lin,Han; Hu,Guo-Xin; Su,Ying; Zhou,Hong-Yu; Lian,Qing-Quan; Cai,Hui; Hardy,Dianne O.; Gu,Ding-Ying; Ge,Renshan
Journal of Steroid Biochemistry and Molecular Biology 113(3-5): 177-181
Publication date: 2009
Gossypol has been proven to be a very effective male contraceptive. However, clinical trials showed that the major side effect of gossypol was hypokalemia. Gossypol occurs naturally as enantiomeric mixtures of (+)-gossypol and (-)-gossypol. The (-)-gossypol is found to be the active component of antifertility. 11ß-Hydroxysteroid dehydrogenase 2 (11ßHSD2) has been demonstrated to be a mineralocorticoid receptor (MR) protector by inactivating active glucocorticoids including corticosterone (CORT) in rats, and therefore mutation or suppression of 11ßHSD2 causes hypokalemia and hypertension. In the present study, the potency of gossypol enantiomers was tested for the inhibition of 11ßHSD1 and 2 in rat and human. Both (+) and (-)-gossypols showed a potent inhibition of 11ßHSD2 with the half maximal inhibitory concentration (IC) of 0.61 and 1.33 µM for (+) and (-)-gossypols, respectively in rats and 1.05 and 1.90 µM for (+) and (-)-gossypols, respectively in human. The potency of gossypol to inhibit 11ßHSD1 was far less; the IC was =100 µM for racemic gossypol. The gossypol-induced hypokalemia is likely associated with its potent inhibition of kidney 11ßHSD2.
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