Androstenedione increases thromboxane A2 receptors in human erythroleukemia cells.
Previous studies have demonstrated an increased thromboxane A2 (TXA2) receptor expression in human erythroleukemia (HEL) cells and rat aortic smooth muscle (RASM) cells in response to testosterone treatment. HEL cells have served as a model for megakaryocytes, the progenitor cell for platelets. Platelets have previously been shown to convert androstenedione to testosterone. This study investigated the effects of androstenedione on the TXA2 receptor density in HEL and cultured RASM cells. Both cell lines were incubated with vehicle, 150 nM testosterone or 250, 500 or 750nM androstenedione for 48 hours. Co-incubation with testosterone or androstenedione significantly (p<0.05) increased the maximum number of TXA2 binding sites (Bmax) in HEL cells compared to controls. There was no significant change in Kd values. In a separate series of experiments, HEL cells were incubated with the androgen receptor antagonist hydroxyflutamide (2.5mM). Treatment with androstenedione (500nM) significantly (p<0.05) increased the Bmax value by 35% compared to control and hydroxyflutamide completely antagonized this effect of androstenedione. Incubation with hydroxyflutamide alone had no effect on the Bmax values compared to control. RASM cells also showed an increase in Bmax values by 25% and 23% over control (95+/-6.6, 118+/-7.2 and 117+/-5.1 fmoles/mg protein, control, testosterone and androstenedione, n=3). Both cell lines converted androstenedione to testosterone. The results raise the possibility that the adrenal androgen, androstenedione can regulate the expression of TXA2 receptors either on its own or via conversion to testosterone and through an androgen receptor.
Zucker
T P
TP
Department of Pharmacology, Medical University of South Carolina, Charleston, USA.
Higashiura
K
K
Mathur
R S
RS
Halushka
P V
PV
D000726:Androgen Antagonists / Q000494:pharmacology; D000735:Androstenedione / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000726:Androgen Antagonists; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002227:Carbazoles; D005231:Fatty Acids, Unsaturated; D007457:Iodine Radioisotopes; D017482:Receptors, Thromboxane; C069994:L 657925; C061750:7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid; C014290:hydroxyflutamide; D013739:Testosterone; D000735:Androstenedione; D005485:Flutamide; D007213:Indomethacin