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Endocrinology, Vol 124, 1942-1948, Copyright © 1989 by Endocrine Society


ARTICLES

Catecholamine-induced heterologous desensitization of rabbit luteal adenylyl cyclase: loss of luteinizing hormone responsiveness is associated with impaired G-protein function

BP Jena and J Abramowitz
Department of Zoology, Iowa State University of Science and Technology, Ames 50011-3223.

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 cyclase 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 to 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 desensitization is associated with altered G-protein function.


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J.-L. Lécrivain, J. Cohen-Tannoudji, M.-T. Robin, N. Coudouel, C. Legrand, and J.-P. Maltier
Molecular Mechanisms of Adenylyl Cyclase Desensitization in Pregnant Rat Myometrium following In Vivo Administration of the ss-Adrenergic Agonist, Isoproterenol
Biol Reprod, July 1, 1998; 59(1): 45 - 52.
[Abstract] [Full Text]




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