Progesterone prevents linkage of rabbit myometrial alpha 2-adrenergic receptors to inhibition of adenylate cyclase.
The uterine response to adrenergic stimulation is determined by the hormonal milieu. This response is particularly well characterized in the rabbit. In this species, as in humans, the response of the uterus to sympathetic stimulation is alpha-adrenergically mediated contraction with elevated circulating estrogen. However, with progesterone predominance, similar stimulation inhibits uterine contractions, a response mediated by beta-adrenergic receptors acting through their second message, cyclic adenosine monophosphate. We studied the mechanisms by which sex steroids regulate myometrial adrenergic responses. In this study, we questioned whether part of the effect of sex steroids could be explained by an alteration of the coupling of the alpha 2-adrenergic receptor to the inhibition of adenylate cyclase. We found that in the progesterone-treated rabbit, although alpha 2-receptors are present, they are not linked to inhibition of cyclic adenosine monophosphate synthesis. The net synthesis of cyclic adenosine monophosphage in response to endogenous catecholamines is determined by their activation of beta-adrenergic receptors to increase and alpha 2-receptors to decrease cyclic adenosine monophosphate formation. Thus the uncoupling of alpha 2-receptors contributes to increased intracellular cyclic adenosine monophosphate in myometrium of progesterone-treated animals consistent with the reported predominance of beta-adrenergic contractile responses in this setting.
Wu
Y Y
YY
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143-0550.
Riemer
R K
RK
Goldfien
A
A
Roberts
J M
JM
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism* / Q000502:physiology
D000067956:Adenylyl Cyclase Inhibitors; D004967:Estrogens; D011942:Receptors, Adrenergic, alpha; D011374:Progesterone; D000262:Adenylyl Cyclases