ACUTE EFFECTS OF PROGESTERONE ON GLUCOSE-METABOLISM IN RAT ADIPOCYTES- ARE THEY MODULATED BY ENDOGENOUS ADENOSINE

Progesterone rapidly inhibits glucose oxidation of isolated rat adipoc ytes. Because this inhibition is triggered by endogenous adenosine, th e present study was designed to examine the effect of the steroid on c yclic adenosine monophosphate (cAMP) accumulation, its relation to lip olysis, and the possible participation of adenosine. The results stron gly indicate that physiological concentrations of progesterone increas e the release of adenosine by isolated adipocytes, with maximal releas e at the end of a 20-minute incubation. Progesterone decreased both cA MP levels and lipolysis in quiescent adipocytes or in adipocytes stimu lated by isoproterenol, The increase of endogenous adenosine may expla in the decline of cAMP and glycerol levels observed with progesterone. The effects of the steroid on lipolysis disappeared when adenosine wa s hydrolyzed by adenosine deaminase (ADA). On the other hand, in the a bsence of endogenous adenosine, the effect of progesterone on the cAMP level was decreased only in isoproterenol-stimulated cells. The inhib itory effects of progesterone on cAMP and glycerol production seem not to be related directly to the adenosine A(1) receptor, for selective A(1) receptor antagonists (8-cyclopentyl-1,3-dipropylxanthine [DPCPX] and CP 68,247) did not counteract these effects. However, mechanisms m ediated by guanyl nucleotide binding proteins cannot be excluded. The decrease of cAMP and of lipolysis may be related to a stimulation of p hosphodiesterases (PDEs). When PDEs I (Ca2+ - calmodulin-regulated PDE family) were blocked by a selective inhibitor (CP 41,757), the proges terone inhibitory effect persisted, suggesting that PDEs I are not reg ulated by the steroid. On the other hand, the progesterone effect on c AMP accumulation but not on lipolysis disappeared in the presence of a selective inhibitor of the PDE IV family (cAMP-dependent-specific fam ily), Ro 20-1724. When the specific inhibitor of PDE I or PDE IV was c ombined with ADA, the progesterone effect on cAMP disappeared. Taken t ogether, these results suggest that the progesterone inhibitory action on cAMP levels was not mediated through A(1) receptors or through act ivation of PDE I, but may be related to PDE IV activities. The progest erone effect on lipolysis seemed not to be directly related to changes in cAMP levels; an effect on PDE III activities in relation with the increase of adenosine release cannot be excluded. Copyright (C) 1997 b y W.B. Saunders Company.