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GLUCOCORTICOID ACTIVITY OF VARIOUS PROGESTERONE ANALOGS: CORRELATION BETWEEN SPECIFIC BINDING IN THYMUS AND LIVER AND BIOLOGIC ACTIVITY *
Author(s) -
DiSorbo Dennis,
Rosen Fred,
McPartland Richard P.,
Milholland Richard J.
Publication year - 1977
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1977.tb29429.x
Subject(s) - medicine , endocrinology , glucocorticoid , tyrosine aminotransferase , steroid , alpha (finance) , in vivo , testosterone (patch) , glucocorticoid receptor , chemistry , in vitro , antiglucocorticoid , biological activity , beta (programming language) , biology , hormone , biochemistry , enzyme , enzyme inducer , construct validity , nursing , microbiology and biotechnology , patient satisfaction , computer science , programming language
When tested in an in vitro assay system, progesterone and various analogs of this steroid were shown to compete with [3H] triamcinolone acetonide (TA) for specific glucocorticoid receptors in both rat liver and thymus. Of these analogs, the following derivatives of progesterone were potent competitors of TA binding and, when injected into adrenalectomized rats, induced regression of the thymus and marked increases in hepatic tyrosine aminotransferase activity: 11 beta-hydroxyl, 6 alpha-methyl, 6 alpha, 16 alpha-dimethyl, and 6 alpha-methyl-17 alpha-hydroxyl. In contrast, progesterone, 16 alpha-methyl, and 17 alpha-hydroxy progesterone competed with TA in vitro but failed to elicit either gluco- or antiglucocorticoid activity in vivo. Also, we observed that the oral contraceptive 6 alpha-methyl-17-(1-propynyl)testosterone competes very effectively with TA in a cell-free preparation of rat liver and induces an increase in hepatic tyrosine aminotransferase activity. The 11 beta-hydroxyl group has previously been thought to be essential for glucocorticoid activity. Our studies indicate that substitution of progesterone or testosterone with a 6 alpha-methyl group negates the need for an 11 beta-hydroxyl substitutuent as a prerequisite for glucocorticoid activity.