Stimulation of the binding properties of adult rat corticosteroid-binding globulin by a lipolysis-induced rise in plasma free fatty acids.
In vitro studies have shown that FFA induce conformational changes in human corticosteroid-binding globulin (CBG). We increased the plasma FFA concentrations of adult male rats by injecting heparin to determine whether such changes in CBG binding and immunological properties also occur in vivo. The in vivo transient activation of lipase by heparin produced a large increase in plasma FFA at 10 and 20 min (P < 0.01), which was maximal at 60 min (P < 0.005) and remained elevated at 120 min (P < 0.01) postinjection. This rise in FFA was associated with a 2- to 3-fold increase in the binding indices (C values; liters per g) of corticosterone (B) and progesterone to CBG 60-120 min postinjection (P < 0.001). There was a good positive correlation (r = 0.85) between the increase in B binding and the rise in plasma FFA in heparin-treated rats. The enhanced B binding to CBG resulted from a 2-fold increase in the apparent number of binding sites, without any significant change in the affinity constant (Ka). FFA extracted from postheparin plasma and a standard FFA mixture induced similar changes in B binding to purified mature rat CBG. The immunological behavior of CBG was not significantly changed after heparin-induced lipolysis, but the immunoreactivity of CBG from heparin-treated rats was more reduced by incubation with exogenous FFA than that from controls. FFA extracted from the plasma of heparin-treated rats and a standard FFA mixture both produced a dose-dependent drop in the immunodetection of pure CBG. These binding and immunological studies indicate that FFA mediate conformational changes in rat CBG in vivo. Thus, FFA, in addition to their roles as metabolic energy sources and components of complex lipids, can be rapid potent endogenous modulators of steroid-protein interactions.
Haourigui
M
M
U-224 INSERM, Faculté de Médecine Xavier Bichat, Laboratoire de Biochimie, Paris, France.
Martin
M E
ME
Thobie
N
N
Benassayag
C
C
Nunez
E A
EA
D000818:Animals; D003345:Corticosterone / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D007122:Immunoelectrophoresis; D007700:Kinetics; D008049:Lipase / Q000097:blood; D008066:Lipolysis; D008297:Male; D011374:Progesterone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014156:Transcortin / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D011374:Progesterone; D006493:Heparin; D014156:Transcortin; D008049:Lipase; D003345:Corticosterone