INFLUENCE OF CALF SERUM ON GLUCOCORTICOID-RESPONSES OF CERTAIN PROGESTERONE DERIVATIVES

The following in vitro glucocorticoid (GC) parameters of progesterone (P), 1-ene progesterone (Delta P), 11 beta-hydroxyprogesterone (HOP), 11 beta-1-ene progesterone (Delta HOP) and dexamethasone (Dexa) were a ssayed in the presence or absence of bovine calf serum (BCS): binding to thymus cytosol, dissociation of the glucocorticoid receptor (GR)-he at shock protein 9O (hsp90) complex (diss.), tyrosine aminotransferase (TAT) induction in hepatocytes and the inhibition of H-3-uridine and S-35-methionine uptake by thymocytes. Without BCS, steroids were in mo st cases active in this general order: Dex > Delta HOP > HOP > Delta P > P. BCS abolished all activities in P and Delta P, but left them una ltered in all other steroids, except diss. in HOP, which diminished in termediately. Binding of P, Delta P, HOP and Delta HOP to GR and CBG p aralleled their in vivo activating effects on glycogen deposition. Con clusions: in this steroid series, BCS, but not CBG, inhibits GC respon ses of P and Delta P. 11-beta hydroxylation frees those molecules from the inhibitory effects of BCS. (C) 1998 Elsevier Science Ltd. All rig hts reserved.