HORMONAL REGULATION OF INTESTINAL lip-HYDROXYSTEROID DEHYDROGENASE J. P&ha’, I. MikSik, V. Lisa and I. Pohlova
نویسندگان
چکیده
We have previously demonstrated the developmental increase of the activity of 11 P-hydroxysteroid dehydrogenase (11 PHSD) in the rat ileum which correlated with the developmental surge of plasma concentrations of corticosteroids, thyroid hormones and insulin. To ascertain whether these hormones directly stimulate 1lPHSD activity we used explant cultures of ileum and distal colon. The intestinal segments of young, 7-day-old rats, were cultured 48 hours in the presence of aldosterone (lo-’ M), dexamethasone ( 10m7 M), triiodothyronine (low7 M) or insulin (lo-’ M) and 11 PHSD activity was evaluated by measuring the conversion of [3H]corticosterone to [3H]1 1-dehydrocorticosterone. The activity of 1lPHSD was significantly increased following 48 h treatment with dexamethasone and aldosterone, whereas insulin and triiodothyronine were without any effect. Corticosterone oxidation was inhibited by carbenoxolone and progesterone. It is being concluded, that both glucocorticoids and mineralocorticoids but not insulin or triiodothyronine induce intestinal 1 IPHSD activity.
منابع مشابه
Intestinal inflammation modulates expression of 11beta-hydroxysteroid dehydrogenase in murine gut.
The effect of glucocorticoids is controlled at the pre-receptor level by the activity of 11beta-hydroxysteroid dehydrogenase (11HSD). The isoform 11HSD1 is an NADP+ -dependent oxidoreductase, usually reductase, that amplifies the action of glucocorticoids due to reduction of the biologically inactive 11-oxo derivatives cortisone and 11-dehydrocorticosterone to cortisol and corticosterone. The N...
متن کاملConformational flexibility in crystal structures of human 11beta-hydroxysteroid dehydrogenase type I provide insights into glucocorticoid interconversion and enzyme regulation.
Human 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1) is an ER-localized membrane protein that catalyzes the interconversion of cortisone and cortisol. In adipose tissue, excessive cortisol production through 11beta-HSD1 activity has been implicated in the pathogenesis of type II diabetes and obesity. We report here biophysical, kinetic, mutagenesis, and structural data on two ternary ...
متن کاملRegulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines.
Patients with glucocorticoid excess develop central obesity, yet in simple obesity, circulating glucocorticoid levels are normal. We have suggested that the increased activity and expression of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) generating active cortisol from cortisone within adipose tissue may be crucial in the pathogenesis of obesity. In this study primary cul...
متن کاملIn vivo footprinting of the human 11beta-hydroxysteroid dehydrogenase type 2 promoter: evidence for cell-specific regulation by Sp1 and Sp3.
11beta-Hydroxysteroid dehydrogenase type 2 is selectively expressed in aldosterone target tissues, where it confers aldosterone selectivity for the mineralocorticoid receptor by inactivating 11beta-hydroxyglucocorticoids with a high affinity for the mineralocorticoid receptor. The present investigation aimed to elucidate the mechanisms accounting for the rigorous control of the HSD11B2 gene in ...
متن کاملThe role of 11 beta-hydroxysteroid dehydrogenase in maturation of the intestine.
Glucocorticoids promote the development of many organs including intestine. At the cellular level, the activity of glucocorticoids is regulated by 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) which converts active glucocorticoids to inactive metabolites. As 11 beta HSD is also expressed in the intestine, this enzyme may be an important regulator of intestinal maturation. To investigate th...
متن کامل