Endocrinology, Vol 127, 2578-2586, Copyright © 1990 by Endocrine Society

ARTICLES

Opposing effects of ethanol on pig ovarian adenylyl cyclase desensitized by human choriogonadotropin or isoproterenol

RC Ekstrom and M Hunzicker-Dunn
Department of Cell, Molecular, and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611.

Pig ovarian follicular membranes contain a gonadotropin-responsive adenylyl cyclase, which becomes partially desensitized (approximately 40%) upon a 40-min incubation with a saturating concentration of human (h) CG. This in vitro desensitization is time and hormone dependent and also requires the presence of micromolar concentrations of GTP. In this report we show that 10% ethanol present during the desensitization phase of the incubation increases the extent of hCG-induced desensitization of adenylyl cyclase by 2-fold. Ethanol shortened the time necessary to reach maximal hCG-induced desensitization from 20 to 10 min, but had no effect on the dose dependency for GTP. In addition, ethanol had no effect on the affinity of the LH/hCG receptor for 125I- hCG but did cause an increase in the ED50 of hCG for inducing desensitization from 0.25 to 0.75 nM. Interestingly, ethanol decreased the apparent number of LH/hCG-receptor sites by 55%, yet the control hCG-sensitive adenylyl cyclase activity was not reduced. The "hyperdesensitized" state achieved in the presence of ethanol could not be reversed by washing the membranes and incubating them in ethanol- free medium. NaF-sensitive adenylyl cyclase was also not impaired in hCG-desensitized membranes from control or ethanol-treated samples. Thus, hCG-induced desensitization was not due to a defect in the functioning of the stimulatory guanine nucleotide-binding regulatory protein (G8) or catalytic subunits, but rather was caused by an impairment of the coupling of the lutropin (LH)/hCG receptor with G8, which was exacerbated further by ethanol. In spite of the effect of ethanol on hCG-induced desensitization, this agent had an inhibitory effect on isoproterenol-induced desensitization of isoproterenol- responsive luteal adenylyl cyclase. These results indicate that membrane fluidity is important in modulating the structure and functional interaction of the LH/hCG receptor with G8 because ethanol is a well known lipid-fluidizing agent. The resistance to ethanol potentiation of desensitization of the isoproterenol-sensitive adenylyl cyclase suggests that there are differences between the LH/hCG- and beta-adrenergic receptors in factors controlling their structures and or interactions with G proteins, and that there is a fundamental difference in their mechanisms of desensitization.

This article has been cited by other articles:

				M. Hunzicker-Dunn, G. Barisas, J. Song, and D. A. Roess Membrane Organization of Luteinizing Hormone Receptors Differs between Actively Signaling and Desensitized Receptors J. Biol. Chem., October 31, 2003; 278(44): 42744 - 42749. [Abstract] [Full Text] [PDF]

				S. Mukherjee, K. Palczewski, V. V. Gurevich, and M. Hunzicker-Dunn beta -Arrestin-dependent Desensitization of Luteinizing Hormone/Choriogonadotropin Receptor Is Prevented by a Synthetic Peptide Corresponding to the Third Intracellular Loop of the Receptor J. Biol. Chem., May 7, 1999; 274(19): 12984 - 12989. [Abstract] [Full Text] [PDF]

				R. M. Rajagopalan-Gupta, S. Mukherjee, X. Zhu, Y.-K. Ho, H. Hamm, M. Birnbaumer, L. Birnbaumer, and M. Hunzicker-Dunn Roles of Gi and Gq/11 in Mediating Desensitization of the Luteinizing Hormone/Choriogonadotropin Receptor in Porcine Ovarian Follicular Membranes Endocrinology, April 1, 1999; 140(4): 1612 - 1621. [Abstract] [Full Text]

				S. Mukherjee, K. Palczewski, V. Gurevich, J. L. Benovic, J. P. Banga, and M. Hunzicker-Dunn A direct role for arrestins in desensitization of the luteinizing hormone/choriogonadotropin receptor in porcine ovarian follicular membranes PNAS, January 19, 1999; 96(2): 493 - 498. [Abstract] [Full Text] [PDF]

				M. L. G. Lamm, R. M. Rajagopalan-Gupta, and M. Hunzicker-Dunn Epidermal Growth Factor-Induced Heterologous Desensitization of the Luteinizing Hormone/Choriogonadotopin Receptor in a Cell-Free Membrane Preparation Is Associated with the Tyrosine Phosphorylation of the Epidermal Growth Factor Receptor Endocrinology, January 1, 1999; 140(1): 29 - 36. [Abstract] [Full Text]

				R. M. Rajagopalan-Gupta, M. L. G. Lamm, S. Mukherjee, M. M. Rasenick, and M. Hunzicker-Dunn Luteinizing Hormone/Choriogonadotropin Receptor-Mediated Activation of Heterotrimeric Guanine Nucleotide Binding Proteins in Ovarian Follicular Membranes Endocrinology, November 1, 1998; 139(11): 4547 - 4555. [Abstract] [Full Text] [PDF]