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

• Published in: The Journal of steroid biochemistry and molecular biology 1998-08, Vol.66 (4), p.211-216
• Main Authors: Vicent, G.P., Burton, G., Ghini, A., Lantos, C.P., Galigniana, M.D.
• Format: Article
• Language: English
• Subjects: Adrenalectomy; Animals; Biological and medical sciences; Blood; Cattle; Cell physiology; Cells, Cultured; Corticosterone - metabolism; Cytosol - metabolism; Dexamethasone - pharmacology; Enzyme Induction; Fundamental and applied biological sciences. Psychology; Hormonal regulation; HSP90 Heat-Shock Proteins - metabolism; Liver - drug effects; Liver - enzymology; Liver - metabolism; Liver Glycogen - biosynthesis; Male; Methionine - metabolism; Mice; Mice, Inbred BALB C; Molecular and cellular biology; Progesterone - analogs & derivatives; Progesterone - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Glucocorticoid - metabolism; Structure-Activity Relationship; Thymus Gland - drug effects; Thymus Gland - metabolism; Transcortin - metabolism; Tyrosine Transaminase - biosynthesis; Uridine - metabolism
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(98)00040-5

The following in vitro glucocorticoid (GC) parameters of progesterone (P), 1-ene progesterone (ΔP), 11 β-hydroxyprogesterone (HOP), 11 β-1-ene progesterone (ΔHOP) 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 9O (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>ΔHOP>HOP>ΔP>P. BCS abolished all activities in P and ΔP, but left them unaltered in all other steroids, except diss. in HOP, which diminished intermediately. Binding of P, ΔP, HOP and ΔHOP 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 ΔP. 11- β hydroxylation frees those molecules from the inhibitory effects of BCS.