Skip to main content
NCBI home page
Transactions of the American Clinical and Climatological Association logoLink to Transactions of the American Clinical and Climatological Association
. 1994;105:95–103.

The Gordon Wilson Lecture. Regulation of thromboxane A2 receptors by testosterone: implications for steroid abuse and cardiovascular disease.

P V Halushka 1, A Masuda 1, K Matsuda 1
PMCID: PMC2376721  PMID: 7974982

Abstract

Thromboxane A2 (TXA2), a platelet aggregator and vasoconstrictor, has been implicated as a potential pathophysiologic mediator of a wide variety of cardiovascular diseases. It is well established that men are at greater risk for cardiovascular disease compared to premenopausal females. Abuse of androgenic/anabolic steroids has been associated with thrombotic cardiovascular diseases in young male athletes. These observations along with several others have led to the hypothesis that testosterone may regulate the expression of TXA2 receptors. Rat aortic smooth muscle cells (RASMC) and human erythroleukemia cells (HEL), a megakaryocyte-like cell, were incubated with testosterone. TXA2 receptor affinity (Kd) and density (Bmax) were determined via equilibrium binding experiments using the radiolabeled TXA2 mimetic [125I]-BOP. Testosterone significantly increased the Bmax without any significant change in Kd. Hydroxyflutamide (1 microM), an androgen receptor antagonist, completely blocked the effect of testosterone. Dihydrotestosterone, the active metabolite of testosterone also increased Bmax in a concentration-dependent manner and was more potent than testosterone. These observations along with several others are consistent with the notion that androgenic steroids may regulate the expression of functional TXA2 receptors in HEL and RASMC. These results raise the possibility that the increase in TXA2 receptor density induced by testosterone may contribute to its thrombotic potential in cardiovascular diseases.

Full text

PDF
95

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carroll J. E., Goodfriend T. L. Androgen modulation of adrenal angiotensin receptors. Science. 1984 Jun 1;224(4652):1009–1011. doi: 10.1126/science.6326265. [DOI] [PubMed] [Google Scholar]
  2. Ferenchick G. S. Are androgenic steroids thrombogenic? N Engl J Med. 1990 Feb 15;322(7):476–476. doi: 10.1056/NEJM199002153220717. [DOI] [PubMed] [Google Scholar]
  3. Ferenchick G., Schwartz D., Ball M., Schwartz K. Androgenic-anabolic steroid abuse and platelet aggregation: a pilot study in weight lifters. Am J Med Sci. 1992 Feb;303(2):78–82. doi: 10.1097/00000441-199202000-00002. [DOI] [PubMed] [Google Scholar]
  4. Frankle M. A., Eichberg R., Zachariah S. B. Anabolic androgenic steroids and a stroke in an athlete: case report. Arch Phys Med Rehabil. 1988 Aug;69(8):632–633. [PubMed] [Google Scholar]
  5. Geller J. Effect of finasteride, a 5 alpha-reductase inhibitor on prostate tissue androgens and prostate-specific antigen. J Clin Endocrinol Metab. 1990 Dec;71(6):1552–1555. doi: 10.1210/jcem-71-6-1552. [DOI] [PubMed] [Google Scholar]
  6. Halushka P. V., Mais D. E., Mayeux P. R., Morinelli T. A. Thromboxane, prostaglandin and leukotriene receptors. Annu Rev Pharmacol Toxicol. 1989;29:213–239. doi: 10.1146/annurev.pa.29.040189.001241. [DOI] [PubMed] [Google Scholar]
  7. Johnson M., Ramey E., Ramwell P. W. Androgen-mediated sensitivity in platelet aggregation. Am J Physiol. 1977 Apr;232(4):H381–H385. doi: 10.1152/ajpheart.1977.232.4.H381. [DOI] [PubMed] [Google Scholar]
  8. Liang T., Cascieri M. A., Cheung A. H., Reynolds G. F., Rasmusson G. H. Species differences in prostatic steroid 5 alpha-reductases of rat, dog, and human. Endocrinology. 1985 Aug;117(2):571–579. doi: 10.1210/endo-117-2-571. [DOI] [PubMed] [Google Scholar]
  9. Mais D. E., Yoakim C., Guindon Y., Gillard J. W., Rokach J., Halushka P. V. Photoaffinity labelling of the human platelet thromboxane A2/prostaglandin H2 receptor. Biochim Biophys Acta. 1989 Jul 11;1012(2):184–190. doi: 10.1016/0167-4889(89)90094-3. [DOI] [PubMed] [Google Scholar]
  10. Martin P., Papayannopoulou T. HEL cells: a new human erythroleukemia cell line with spontaneous and induced globin expression. Science. 1982 Jun 11;216(4551):1233–1235. doi: 10.1126/science.6177045. [DOI] [PubMed] [Google Scholar]
  11. Masuda A., Mathur R., Halushka P. V. Testosterone increases thromboxane A2 receptors in cultured rat aortic smooth muscle cells. Circ Res. 1991 Sep;69(3):638–643. doi: 10.1161/01.res.69.3.638. [DOI] [PubMed] [Google Scholar]
  12. Matsuda K., Mathur R. S., Duzic E., Halushka P. V. Androgen regulation of thromboxane A2/prostaglandin H2 receptor expression in human erythroleukemia cells. Am J Physiol. 1993 Dec;265(6 Pt 1):E928–E934. doi: 10.1152/ajpendo.1993.265.6.E928. [DOI] [PubMed] [Google Scholar]
  13. Mayeux P. R., Mais D. E., Carr C., Halushka P. V. Human erythroleukemia cells express functional thromboxane A2/prostaglandin H2 receptors. J Pharmacol Exp Ther. 1989 Sep;250(3):923–927. [PubMed] [Google Scholar]
  14. Morinelli T. A., Oatis J. E., Jr, Okwu A. K., Mais D. E., Mayeux P. R., Masuda A., Knapp D. R., Halushka P. V. Characterization of an 125I-labeled thromboxane A2/prostaglandin H2 receptor agonist. J Pharmacol Exp Ther. 1989 Nov;251(2):557–562. [PubMed] [Google Scholar]
  15. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  16. Myers A., Penhos J., Ramey E., Ramwell P. Thromboxane agonism and antagonism in a mouse sudden death model. J Pharmacol Exp Ther. 1983 Feb;224(2):369–372. [PubMed] [Google Scholar]
  17. Nagelberg S. B., Laue L., Loriaux D. L., Liu L., Sherins R. J. Cerebrovascular accident associated with testosterone therapy in a 21-year-old hypogonadal man. N Engl J Med. 1986 Mar 6;314(10):649–650. doi: 10.1056/nejm198603063141017. [DOI] [PubMed] [Google Scholar]
  18. Penhos J. C., Rabbani F., Myers A., Ramey E., Ramwell P. The role of gonadal steroids in arachidonate-induced mortality in mice. Proc Soc Exp Biol Med. 1981 May;167(1):98–100. doi: 10.3181/00379727-167-41132. [DOI] [PubMed] [Google Scholar]
  19. Rockhold R. W. Cardiovascular toxicity of anabolic steroids. Annu Rev Pharmacol Toxicol. 1993;33:497–520. doi: 10.1146/annurev.pa.33.040193.002433. [DOI] [PubMed] [Google Scholar]
  20. Rosenblum W. I., el-Sabban F., Nelson G. H., Allison T. B. Effects in mice of testosterone and dihydrotestosterone on platelet aggregation in injured arterioles and ex vivo. Thromb Res. 1987 Mar 15;45(6):719–728. doi: 10.1016/0049-3848(87)90082-x. [DOI] [PubMed] [Google Scholar]
  21. Uzunova A. D., Ramey E. R., Ramwell P. W. Arachidonate-induced thrombosis in mice: effects of gender or testosterone and estradiol administration. Prostaglandins. 1977 May;13(5):995–1002. doi: 10.1016/0090-6980(77)90229-5. [DOI] [PubMed] [Google Scholar]
  22. Uzunova A. D., Ramey E. R., Ramwell P. W. Gonadal hormones and pathogenesis of occlusive arterial thrombosis. Am J Physiol. 1978 Apr;234(4):H454–H459. doi: 10.1152/ajpheart.1978.234.4.H454. [DOI] [PubMed] [Google Scholar]

Articles from Transactions of the American Clinical and Climatological Association are provided here courtesy of American Clinical and Climatological Association

RESOURCES