Inhibition of 11β-Hydroxysteroid Dehydrogenase Activity in Rat and Mouse Tissuesin Vitroandin Vivo

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Abstract
Dehydrogenation of the 11[beta]-hydroxyl group of cortisol to form cortisone proceeded most rapidly in vitro in kidney tissue of mice and rats; spleen, thymus and lymphosarcoma of mice were less active, while skeletal muscle and tumor stroma of mice and rats and rat thymus reticular tissue showed low activity. Dehydrogenationwasinhibitedconsiderablyby 11-epi-corti-sol, 11-epi-prednisolone and 11[alpha]-hydroxyprogeslerone in concentrations up to 9 times that of cortisol (9 xF). Renal veinbloodcollectedafter injection of cortisol- 4- C14 contained cortisone, and simultaneous injection of inhibitors (up to 11 x F) reduced the ratio cortisone/cortisol from .19 to .09 in mice and from .14 to .06 in rats. Inhibitors (4 x F) injected subcutaneously enhanced 2-told the involutionary effect of standard doses of cortisol and prednisolone on mouse thymus, which contains considerable enzyme activity, but not rat thymus, which contains little. Growth of steroid-resistant mouse lymphosarcoma P1798 was not affected by compounds which inhibited enzyme activity in vitro. It was concluded that 11[beta]-hydroxysteroid dehydrogenase activity is present in several tissues, can be demonstrated in vivo in kidney, probably plays a role in regulating lymphoid tissue, at least in mice, but is not involved critically in the resistance of tumors to steroids.

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