REGULATION OF THE GTP-BINDING PROTEIN-BASED ANTILIPOLYTIC SYSTEM OF SHEEP ADIPOCYTES BY GROWTH-HORMONE

Chronic exposure of sheep adipose tissue to growth hormone (GH) in vit ro decreases the ability of the adenosine analogue, N-6-phenylisopropy ladenosine (PIA), to inhibit isoprenaline-stimulated lipolysis by a me chanism which is dependent on both gene transcription and protein seri ne/threonine phosphorylation. The inhibition is not due to a change in Ligand binding to the adenosine receptor, the amounts of the three is oforms of the inhibitory GTP-binding protein, G(i), or the maximum (fo rskolin-stimulated) adenylate cyclase activity. The ability of GH to m odulate the PIA-activated adenosine receptor to stimulate dissociation of heterotrimeric G(i) was assessed by measurement of pertussis toxin -catalysed ADP-ribosylation of G(i); GH does not appear to alter the i nteraction between the activated receptor and G(i). The ability of GH to alter the ability of activated G(i) to inhibit adenylate cyclase ac tivity was assessed by measuring the ability of a GTP analogue, guanos ine 5'-[beta gamma-imido]triphosphate (p[NH]ppG), to inhibit forskolin -stimulated adenylate cyclase activity; chronic exposure to GH prevent ed this effect of p[NH]ppG. Thus the attenuation of the inhibition of Lipolysis by PIA by chronic exposure of adipocytes to GH appears to be due to an impairment in the interaction between adenylate cyclase and the alpha subunit of one or more isoforms of G(i).