Growth hormone inhibits activation of phosphatidylinositol phospholipase C in adipose plasma membranes: evidence for a growth hormone-induced change in G protein function.
Pituitary growth hormone (GH) functions physiologically to oppose the actions of insulin on carbohydrate and lipid metabolism by interfering with metabolic events that occur after insulin binds to its receptor. Which postreceptor effects are involved is presently unknown. Recently, we found that insulin rapidly stimulates a phosphatidylinositol phospholipase C (PI-PLC) in adipose tissue of obese (ob/ob) mice and that this effect of insulin is blocked by treatment of the animals with S-carboxymethylated human GH (RCM-hGH), a derivative having mainly anti-insulin activity. The activation of this PI-PLC by insulin is also inhibited by pertussis toxin. Thus, this study was performed to examine whether the inhibitory effect of GH on the activation of this PI-PLC is exerted at the level of signal transmission by guanine nucleotide binding proteins (G proteins). We found that the nonhydrolyzable GTP analogue, guanosine 5'-[gamma-thio]triphosphate, stimulated basal PI-PLC activity in plasma membranes of adipose tissue of saline-treated ob/ob mice, but it did not stimulate the enzyme in adipose membranes from RCM-hGH-treated mice. Also, RCM-hGH treatment markedly inhibited pertussis toxin-catalyzed ADP ribosylation of G protein alpha subunits in the membranes, suggesting some modification of the G proteins by GH. Immunoblot analysis of adipose membranes from saline- and RCM-hGH-treated mice using antiserum AS/7 (anti-Gi1 alpha and anti-Gi2 alpha) or antiserum EC/2 (anti-Gi3 alpha) showed no difference in the amount of Gi alpha-like protein between the groups. These findings suggest that GH interferes with the ability of a putative Gi-like protein to mediate the activation of PI-PLC in adipose membranes without altering the expression of the G protein.
Roupas
P
P
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
Chou
S Y
SY
Towns
R J
RJ
Kostyo
J L
JL
D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D013006:Growth Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D019382:Human Growth Hormone; D007700:Kinetics; D051379:Mice; D008820:Mice, Obese; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values
D006150:Guanine Nucleotides; D006728:Hormones; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013006:Growth Hormone; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D019204:GTP-Binding Proteins; D043265:Phosphatidylinositol Diacylglycerol-Lyase