title: A mechanism for testosterone modulation of alpha-1 adrenergic receptor expression in the DDT1 MF-2 smooth muscle myocyte.
abstract: Previous reports have confirmed that steroid hormones modulate the expression of adrenergic receptors on the surface of smooth muscle myocytes. The present study was undertaken to evaluate the mechanism by which testosterone modulates alpha-1 adrenergic receptor expression in the DDT1 MF-2 transformed smooth muscle cell. Utilizing 3H-prazosin radioligand binding studies, alpha-1 adrenergic receptors were noted to increase more than 2 fold in response to incubation with 10(-8)M testosterone for 96 hours. Dihydrotestosterone similarly stimulated a significant increase in alpha-1 receptors; whereas, estradiol and hydrocortisone appeared to suppress the expression of this receptor in DDT myocytes. The testosterone effect was dose related with a maximal response observed in response to 10(-7)M testosterone at both 48 and 96 hours. Kinetic experiments utilizing 10(-8)M testosterone demonstrated a peak effect on alpha-1 receptor expression at 96 hours, and maintenance of the effect for at least 168 hours (7 days). The testosterone effect was completely prevented at both 48 and 96 hours by inhibition of transcription with actinomycin-D, or inhibition of translation with cycloheximide. Consistent with the receptor binding studies, RNA blotting studies have demonstrated maximal alpha-1 receptor mRNA levels at 48-96 hours of testosterone stimulation. In conclusion, these in vitro experiments have confirmed the physiologic concentrations of testosterone stimulate the increased expression of alpha-1 receptors in the DDT1 MF-2 myocyte after a delay of 48-96 hours; and that this effect appears to be mediated by transcription, translation, and synthesis of new proteins in these genital tract myocytes.
authors.affiliation: Department of Obstetrics and Gynecology, Pritzker School of Medicine, University of Chicago, Illinois.
authors.forename: M
authors.initials: M
authors.lastname: Phillippe
authors.forename: T
authors.initials: T
authors.lastname: Saunders
authors.forename: S
authors.initials: S
authors.lastname: Bangalore
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002461:Cell Line, Transformed; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D009130:Muscle, Smooth / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000096:biosynthesis*; D013739:Testosterone / Q000378:metabolism*
chemical_list: D011942:Receptors, Adrenergic, alpha; D003609:Dactinomycin; D013739:Testosterone; D004958:Estradiol; D003513:Cycloheximide; D006854:Hydrocortisone; D011224:Prazosin