Pohlová I, Miksík I, Pácha J
Institute of Physiology, Czech Academy of Sciences, Prague 4-Krc, Czech Republic.
Mech Ageing Dev. 1997 Nov;98(2):139-50. doi: 10.1016/s0047-6374(97)00079-1.
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 this, we have performed the systematic study of the development of intestinal 11 beta HSD activity and its cofactor preference as well as of the effect of 11 beta HSD inhibition by carbenoxolone on postnatal development of sucrase, alkaline phosphatase and Na,K-ATPase in the intestine. The activity of 11 beta HSD was low in ileum of suckling rats and significantly increased during the weaning period. In colon, the activity was already high in suckling rats and gradually rose during the postnatal development. 11 beta HSD activity was undetectable in jejunum both in young and adult rats. At 14.5 nM corticosterone, colonic 11 beta HSD utilized predominantly NAD as a cofactor, but displayed significant sensitivity also to NADP. Ileal 11 beta HSD had similar sensitivity to both cofactors. With NAD as a cofactor, ileal 11 beta HSD had a Km (59 +/- 10 nM) compatible with the colonic enzyme (81 +/- 14 nM). Carbenoxolone administration to suckling and weanling rats in vivo did not result in any changes of sucrase activity in jejunum and ileum, alkaline phosphatase activity in ileum and distal colon or Na,K-ATPase activity in ileum. However, carbenoxolone significantly increased Na,K-ATPase activity in distal colon. Our results indicate that the high-affinity type of 11 beta HSD is expressed not only in colon but also in ileum and that 11 beta HSD is an important factor in the regulation of tissue levels of active glucocorticoids in developing colon but not in the small intestine.
糖皮质激素促进包括肠道在内的许多器官的发育。在细胞水平上，糖皮质激素的活性由11β-羟基类固醇脱氢酶（11βHSD）调节，该酶将活性糖皮质激素转化为无活性代谢物。由于11βHSD也在肠道中表达，这种酶可能是肠道成熟的重要调节因子。为了对此进行研究，我们对肠道11βHSD活性的发育及其辅因子偏好性，以及甘珀酸对11βHSD的抑制作用对肠道中蔗糖酶、碱性磷酸酶和钠钾-ATP酶出生后发育的影响进行了系统研究。11βHSD活性在乳鼠回肠中较低，在断奶期显著增加。在结肠中，该活性在乳鼠中已经很高，并在出生后发育过程中逐渐上升。在幼鼠和成年大鼠的空肠中均未检测到11βHSD活性。在14.5 nM皮质酮存在下，结肠11βHSD主要利用NAD作为辅因子，但对NADP也表现出显著的敏感性。回肠11βHSD对两种辅因子具有相似的敏感性。以NAD作为辅因子时，回肠11βHSD的Km（59±10 nM）与结肠酶（81±14 nM）相当。在体内给乳鼠和断奶大鼠施用甘珀酸，并未导致空肠和回肠中蔗糖酶活性、回肠和远端结肠中碱性磷酸酶活性或回肠中钠钾-ATP酶活性发生任何变化。然而，甘珀酸显著增加了远端结肠中的钠钾-ATP酶活性。我们的结果表明，高亲和力型11βHSD不仅在结肠中表达，也在回肠中表达，并且11βHSD是发育中结肠而非小肠中活性糖皮质激素组织水平调节的重要因素。
