Hormonal regulation of beta-adrenergic receptors in the rat mammary gland during the estrous cycle and lactation: role of sex steroids and prolactin.

To gain further knowledge on the role of ovarian hormones in the regulation of mammary beta-adrenergic receptors, virgin animals were killed during the various phases of the estrous cycle as well as after ovariectomy and treatment with sex steroid. beta-Adrenergic receptor levels fluctuate in the rat mammary gland during the estrous cycle, with higher receptor numbers during the proestrous and estrous phases of the cycle. Ovariectomy caused an almost 50% loss of beta-adrenergic receptor concentration in the mammary gland of virgin rats. Treatment of ovariectomized animals with 17 beta-estradiol or progesterone alone or in combination for 3 weeks induced a marked increase in beta-adrenergic receptor concentration, while administration of the androgen dihydrotestosterone did not modify mammary beta-adrenergic binding sites. While levels of beta-adrenergic receptors in control lactating animals (10 days of lactation) were elevated, chronic treatment with the dopaminergic-mimetic agent 2 alpha-bromoergocryptine (CB-154; for 7 days) reduced beta-adrenergic receptor concentration. Castration of lactating animals decreased beta-adrenergic receptor number to approximately 30% of the value in intact controls, while combined withdrawal of circulating ovarian hormones and inhibition of plasma PRL levels caused an almost complete inhibition of beta-adrenergic receptor concentration. Scatchard analysis of the binding data revealed that the observed alterations in beta-adrenergic receptors resulted from changes in the number of beta-adrenergic binding sites, with no change in binding affinities. The present findings indicate that the beta-adrenergic receptor population of the rat mammary gland is under the control of ovarian hormones and PRL and suggest that circulating or locally released catecholamines could interact with sex steroids and PRL in the regulation of mammary gland growth, differentiation, and activity.