Catecholamine-Induced Heterologous Desensitization of Rabbit Luteal Adenylyl Cyclase: Loss of Luteinizing Hormone Responsiveness Is Associated with Impaired G-Protein Function*

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Abstract
The effects of injecting epinephrine into pseudopregnant rabbits on the luteal adenylyl cyclase system were analyzed. Epinephrine-induced desensitization was heterologous and associated with a reduced response to isoproterenol. LH, NaF, and forskolin. Epinephrine-induced desensitization was rapid in onset, with a maximum decrease in responsiveness 6 h after treatment and responsiveness returning to control levels within 24 h of treatment. The changes in .beta.-adrenergic receptor content paralleled changes in catecholamine responsiveness. The affinity of the .beta.-receptors from treated animals decreased 1.5- to 2-fold before down-regulation. LH receptor number was not altered by epinephrine treatment, although responsiveness to LH was depressed. LH receptor affinity, however, was reduced about 2-fold by epinephrine treatment. Epinephrine treatment also altered G-protein function in corpora lutea, as assessed by reconstitution of adenylyl cyalse activity in S49 cyc- membranes and ADP ribosylation by cholera and pertussis toxins. NaF- and isoproterenol-reconstituting activities of luteal Gs (the stimulatory G-protein of adenylyl cyclase) were depressed for the first 6 h after treatment. The ability of cholera toxin in ADP ribosylate .alpha.s 46 and .alpha.s 45 was reduced 1.5-6 h and 3-12 h, respectively, after epinephrine treatment. The reduced ability of cholera toxin to ADP ribosylate .alpha.s 45 was associated with the decrease in LH receptor affinity after treatment. This supports the contention that .alpha.s 45 preferentially interacts with the LH receptor. These studies demonstrate that the loss of LH responsiveness upon epinephrine-induced heterologous densensitization is associated with altered G-protein function.

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