Influence of calf serum on glucocorticoid-responses of certain progesterone derivatives

VICENT GP, BURTON G, GHINI A, LANTOS CP, GALIGNIANA MD

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 1998 vol. 66 p. 211 - 216

0960-0760

The following in vitro glucocorticoid (GC) parameters of progesterone (P), 1-ene progesterone (deltaP), 11beta-hydroxyprogesterone (HOP), 11beta-1-ene progesterone (deltaHOP) and dexamethasone (Dexa) were assayed in the presence or absence of bovine calf serum (BCS): binding to thymus cytosol, dissociation of the glucocorticoid receptor (GR)-heat shock protein 90 (hsp90) complex (diss.), tyrosine aminotransferase (TAT) induction in hepatocytes and the inhibition of 3H-uridine and 35S-methionine uptake by thymocytes. Without BCS, steroids were in most cases active in this general order: Dex > deltaHOP > HOP > deltaP > P. BCS abolished all activities in P and deltaP, but left them unaltered in all other steroids, except diss. in HOP, which diminished intermediately. Binding of P, deltaP, HOP and deltaHOP to GR and CBG paralleled their in vivo activating effects on glycogen deposition. Conclusions: in this steroid series, BCS, but not CBG, inhibits GC responses of P and deltaP. 11-Beta hydroxylation frees those molecules from the inhibitory effects of BCS.