THE INVOLVEMENT OF THE STIMULATORY G-PROTEIN IN SEXUAL DIMORPHISM OF BETA-ADRENERGIC RECEPTOR-MEDIATED FUNCTIONS IN RAT-LIVER

In rat hepatocytes, beta-adrenergic receptor (beta-AR)-mediated cAMP g eneration was found to be higher in the female than in the male. As co mpared to the male, the number of beta-AR, detected by [I-125]iodocyan opindolol, was elevated in the female. In agonist competition experime nts, the proportion of beta-AR in the high-affinity state was promoted in the female than in the male. The alpha subunit of the stimulatory G protein (Gs alpha) was quantified using ADP-ribosylation catalyzed b y cholera toxin. The amount of Gs alpha, both small, 42 kDa (Gs alpha( S)), and large, 47 kDa (Gs alpha(L)), forms increased in parallel with enhancement of catecholamine-sensitive adenylate cyclase activity in the female. The female showed a disproportionate increase in Gs alpha( L), which is preferentially coupled to beta-AR, compared with Gs alpha (S). In addition, 17 beta-estradiol facilitated isoproterenol-induced cAMP generation in both male and female rats, whereas castration or te stosterone had no effect on this response. It is proposed that the cel lular sites for sexual dimorphism in hepatic beta-adrenergic functions are the coupling state of beta-AR to Gs and the amount of Gs alpha as well as the level of beta-AR.