Molecular Pharmacology, Vol 14, 1054-1062, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Human Chorionic Gonadotropin-Induced Leydig Cell Refractoriness to Gonadotropin Stimulation

¹ Unite de Recherches sur le Contrôle Hormonal des Activités Cellularies, INSERM, U. 162. Hôpital Debrousse, 29 Rue Soeur Bouvier, 69322 Lyon Cedex 1, France

A single injection of 500 IU of human chorionic gonadotropin to intact male rats induced steroidogenic refractoriness of Leydig cells to gonadotropin stimulation. Complete refractoriness to human chorionic gonadotropin both in vivo and in vitro was observed between 12 and 60 hours after the injection. During the same period of time, refractoriness to N⁶,O²-dibutyryl adenosine-3':5'-monophosphate (DbcAMP) in vitro was affected to a smaller degree. Human chorionic gonadotropin binding capacity decreased to less than 10% that of the controls within 12 hours, and remained undetectable until 96 hours after the human chorionic gonadotropin injection. Complete responsiveness to DbcAMP was recovered while the response to human chorionic gonadotropin was still very small and the binding sites were still undetectable. Moreover, full responsiveness to human chorionic gonadotropin was obtained when only 25% of the binding sites were measured. Basal, guanylnucleotide, and sodium fluoride stimulated adenylate cyclase activities, as well as cAMP phosphodiesterase activity of Leydig cell particles from human chorionic gonadotropin-treated rats were at all times similar to untreated animals. Ten international units of human chorionic gonadotropin also induced refractoriness, but for a shorter period of time, and the number of human chorionic gonadotropin binding sites was in this case never less than 30% that of controls.

These data suggest that human chorionic gonadotropin-induced refractoriness of Leydig cells steroidogenesis can be related to at least two phenomena: a decrease in the number of binding sites and an abnormality of some step of steroidogenesis beyond cAMP formation.

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ACKNOWLEDGMENTS We thank Dr. C. Sonnenschein for suggestions in preparing the manuscript and Ms Joëlle Bois for secretarial assistance.

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