Differential effect of adrenocorticosteroids on 11 beta-hydroxysteroid dehydrogenase bioactivity at the anterior pituitary and hypothalamus in rats.
11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) is a microsomal enzyme that catalyzes the dehydrogenation of cortisol (F) to cortisone (E) in man and corticosterone (B) to 11-dehydrocorticosterone (A) in rats. 11 beta-OHSD has been identified in a wide variety of tissues. The differential distribution of 11 beta-OHSD suggests that this enzyme has locally defined functions that vary from region to region. The aim of this study was to investigate the effects of the glucocorticoids B and dexamethasone (DM), the mineralocorticoid deoxycorticosterone (DOC), and the inhibitors of 11 beta-OHSD glycyrrhizic acid (Gl) and glycyrrhetinic acid (GE) on 11 beta-OHSD bioactivity at the hypothalamus (HT) and anterior pituitary (AP). Male Wistar rats were treated with GI or were adrenalectomized (ADX) and treated with either B, DM, or DOC for 7 days. All treatments were in vivo except GE, which was used in vitro. At the end of treatment, homogenates of HT and AP were assayed for 11 beta-OHSD bioactivity, expressed as the percentage conversion of B to A in the presence of NADP, 11 beta-OHSD bioactivity is significantly higher (P < 0.0001) in the AP compared with the HT. Adrenalectomy significantly increased the enzyme activity in the AP (P < 0.05), an effect reversed by B or DM. ADX rats treated with DOC showed decreased enzyme activity in the AP (P < 0.001) but increased the activity in the HT (P < 0.0001). Gl increased activity in both HT and AP, whereas GE decreased activity significantly. We conclude that the modulation of 11 beta-OHSD is both steroid specific and tissue specific.
Idrus
R B
RB
Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Mohamad
N B
NB
Morat
P B
PB
Saim
A
A
Abdul Kadir
K B
KB
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D006913:Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D003900:Desoxycorticosterone; D019695:Glycyrrhizic Acid; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; D003345:Corticosterone