title: Sex steroid regulation of thromboxane A2 receptors in cultured rat aortic smooth muscle cells.
abstract: Thromboxane A2 (TXA2) has been implicated as an important mediator of cardiovascular diseases, and male rat aortas are reported to be more sensitive to it than female aortas. The effects of sex steroids to regulate the expression of TXA2 receptors in cultured male rat aortic smooth muscle cells (RASMC) were determined. TXA2 receptor density (Bmax) and affinity (Kd) were determined via radioligand binding studies with [125I]BOP, a TXA2 receptor agonist. Testosterone increased Bmax in a concentration-dependent manner without any significant change in Kd. Cycloheximide, actinomycin D, and the 5 alpha-reductase inhibitor L645,390 significantly (P < 0.01) blocked the effect of testosterone. Dihydrotestosterone, the active metabolite of testosterone, increased Bmax and was more potent than testosterone. To determine if there is a sex-related difference in response to testosterone, its effect in cultured female RASMC was assessed. Testosterone increased Bmax in female RASMC but the increase was significantly (P < 0.001) less than that seen in male RASMC. These results indicate that androgenic steroids regulate the expression of vascular TXA2 receptors.
authors.affiliation: Department of Pharmacology, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: K
authors.initials: K
authors.lastname: Matsuda
authors.forename: R S
authors.initials: RS
authors.lastname: Mathur
authors.forename: M E
authors.initials: ME
authors.lastname: Ullian
authors.forename: P V
authors.initials: PV
authors.lastname: Halushka
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000378:metabolism; D004958:Estradiol / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007457:Iodine Radioisotopes; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011869:Radioligand Assay; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism / Q000502:physiology; D017482:Receptors, Thromboxane / Q000378:metabolism / Q000502:physiology*; D012737:Sex Factors; D013739:Testosterone / Q000502:physiology
chemical_list: D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D012739:Gonadal Steroid Hormones; D007457:Iodine Radioisotopes; D011945:Receptors, Angiotensin; D017482:Receptors, Thromboxane; D013196:Dihydrotestosterone; C061750:7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid; D013739:Testosterone; D004958:Estradiol