Comparative biochemical study on glucocorticoid metabolism in mammary gland and kidney

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Corticosteroid action is modulated by the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) Two isozymes of 11 beta-HSD are now recognized : 11 beta-HSD-1 is NADP-dependent enzyme with a Km in the micromolar range. 11 beta-HSD-2 is NAD-dependent enzyme with a Km in the nanomolar range. In the liver, 11 beta-HSD-1 is predominant and converts 11-dehydrocorticosterone to corticosterone. On the other hand, in the kidney, the NAD-dependent 11 beta-HSD-2 oxidatively inactivates corticosterone, allowing the nonselective mineralocorticoid receptor to be occupied by mineralocorticoids. The present study was conducted to show that 11 beta-HSD-2 is present in other sodium-transporting epithelia such as those in the mammary gland of mammals and in the reproductive tract of egg-laying birds.The microsome fraction was prepared from homogenates of kidney and various parts of oviduct of Japanese quail, and incubated with traitiated corticosterone for 1 hr at 40 C in the presence or absence of 1 mM NAD.The reaction was stopped, and the steroid was extracted by ethyl acetate. Separation of steroids was performed using a thin-layr chromatography developed in a chloroform-methanol (95 : 5) system. Activity of 11 beta-HSD-2 was determined by measuring the conversion rate of corticosterone to 11-dehydrocorticosterone.Among a number of tissues studied, the shell gland and albumen secreting region of the oviduct showed high activity of 11 beta-HSD-2. In these tissue, radioactive corticosterone was exclusively metabolized to 11-dehydrocorticosterone. On the other hands, infundibulum and isthmus of the oviduct and the vagina contain low activity, indicationg that these parts might not be a target of the mineralocorticoids. Although the process of secretion of albumen and the formation of egg shell is not known to be mediated by mineralocorticoids, our findings indicate that these tissues might be a target of the mineralocorticoids.