Catecholamines directly stimulate GH, ACTH and PRL secretion from rat anterior pituitary through the ß₂-adrenoceptor (AR). We recently showed that gonadotrophs express the ß₁-AR and that glucocorticoids drastically increase its mRNA expression level. The present investigation explores whether ß₁-ARs are functionally coupled to adenylate cyclase. In anterior pituitary cell aggregates the highly selective ß₁-AR antagonists CGP 20712A and ICI 89,406–8a attenuated isoproterenol (ISO)-stimulated cAMP accumulation, but no agonist action of norepinephrine could be detected. Remarkably, CGP 20712A inhibited basal cAMP levels by its own for at least 50%, an action that tended to be more effective in dexamethasone-supplemented medium. The latter effect was abolished by the ß-AR antagonist carvedilol but not by other ß-AR antagonists. Pre-treatment with pertussis-toxin abolished the action of CGP 20712A on basal cAMP. CGP 20712A also attenuated ISO-induced cAMP accumulation in the gonadotroph cell lines T3–1 and LßT2, but not in the somatotroph precursor cell line GHFT and the folliculo-stellate cell line TtT/GF. However, in LßT2 cells CGP 20712A did not inhibit basal cAMP levels by its own.

The present data suggest that ß₁-AR in the anterior pituitary is positively coupled to adenylyl cyclase but is constitutively active in a pertussis toxin-sensitive manner. CGP 20712A may act as an inverse agonist with 50% negative intrinsic activity, suggesting that the ß₁-AR significantly contributes to basal adenylate cyclase activity in the pituitary.