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Disappearance of β- Adrenergic Response of Human Myometrial Adenylate Cyclase at the End of Pregnancy^*

INSERM U.166, Groupe de Recherches sur l'Endocrinologie de la Reproduction, Clinique Uniuersitaire Baudelocque (D.C.) Paris 75014, France

Address requests for reprints to: Dr. Françoise Ferre, INSERM U.166, Groupe de Recherches sur l'Endocrinologie de la Reproduction, Clinique Universitaire, 123 boulevard de Port-Royal, Paris 75014, France.

The density of β-adrenergic receptors in both the outer and inner layers of the human myometrium decreases during the last weeks of pregnancy. Although in preterm myometrium (32–35 weeks of pregnancy) β-adrenergic receptors are positively coupled to adenylate cyclase, we found that isoproterenol, epinephrine, and norepinephrine did not stimulate the enzyme in the inner or outer myometrial layer at term (39–40 weeks of pregnancy). At this stage, the addition of 10^–4 mol/L guanyl-5'-imidodiphosphate increased (from 10^–8 to 10^–4 mol/L) basal adenylate cyclase activity in a dose-dependent manner, indicating that the catalytic component of the enzyme remains linked to the stimulatory guanyl nucleotide binding protein (G_s). Compared to the preterm response, at term the myometrial adenylate cyclase response to 10^–4 mol/L guanyl-5'-imidodiphosphate was decreased, which may reflect a decrease in the amount of functional G_s. Altogether these changes are consistent with reduced G_s coupling to the catalytic component. However, the similarity of the responses of preterm and term myometrium to forskolin excluded the possibility of an alteration of the catalytic component of adenylate cyclase during the last weeks of pregnancy. The fact that a stimulatory effect of isoproterenol on adenylate cyclase was found after islet-activating protein pretreatment indicates that human term myometrium contains a functional inhibitory guanyl nucleotide binding protein which is involved in the modulation of the β-adrenergic adenylate cyclase response.

Our data suggest that modifications in the coupling mechanisms between receptors and the catalytic component are implicated in the loss of β-adrenergic adenylate cyclase stimulation in the myometrium at the end of pregnancy.

^* This work was supported in part by grants from CNAMTSINSERM.

Received August 10, 1988.

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