Mt. Sutterdub et P. Cordoba, ACUTE EFFECTS OF PROGESTERONE ON GLUCOSE-METABOLISM IN RAT ADIPOCYTES- ARE THEY MODULATED BY ENDOGENOUS ADENOSINE, Metabolism, clinical and experimental, 46(6), 1997, pp. 595-604
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.