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Molecular Pharmacology, Vol 15, 439-444, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Differing Specificities in the Desensitization of Ovarian Adenylate Cyclase by Epinephrine and Human Chorionic Gonadotropin

JAMES P. HARWOOD 1, MARIA L. DUFAU 1, and KEVIN J. CATT 1

1 Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 200l4

Adenylate cyclase activity of luteinized ovaries from gonadotropin-primed immature rats was stimulated by luteinizing hormone (LH), epinephrine and prostaglandin E1. Treatment of primed rats with human chorionic gonadotropin (hCG) caused a time-dependent loss of the adenylate cyclase response to LH, and the enzyme also became refractory to stimulation by epinephrine. Conversely, treatment of primed rats with epinephrine caused a time-dependent loss of the adenylate cyclase response to epinephrine, but the enzyme remained responsive to LH. The refractoriness of adenylate cyclase to epinephrine after desensitization by hCG or epinephrine was not reversed by Gpp(NH)p. These studies show that "cross-desensitization" of epinephrine-responsive adenylate cyclase activity in the ovary is induced by LH-receptor interaction, whereas beta-adrenergic desensitization causes more specific refractoriness to epinephrine with no change in the LH receptor activation mechanism. This suggests the existence of fundamental differences in mechanisms of adenylate cyclase activation and/or desensitization by catecholamines and glycoprotein hormones.

Submitted on July 11, 1978
Accepted on September 26, 1978




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