mRNA and protein levels of the stimulatory guanine nucleotide regulatory protein Gs are lower in the testis of obese (ob/ob) mice.

Probing of total testis RNA with a cDNA corresponding to the alpha s subunit of the guanine nucleotide regulatory protein (G-protein) showed that levels of mRNA were markedly reduced in the ob/ob mouse compared to its +/+ control. The lowered level of mRNA resulted in lowered protein synthesis as shown by a marked decrease in both the 48,000 and 42,000 Mr peptides detected by (1) cholera toxin ribosylation, (2) immunodetection with an antibody specific for alpha s. This was not the result of overall lowered protein synthesis since the levels of alpha i2 and the beta subunits were unchanged. In the kidney there was no change in the levels of the alpha s subunit in obese membrane preparations. Lowered levels of alpha s were not correlated with changes in adenylyl cyclase activity. This suggests that in these membranes the G-protein subunit(s) are present in excess compared to the catalytic unit of adenylyl cyclase and that in the testis the G-proteins may be of more importance in other signalling pathways necessary for normal gonadal development and fertility.