Impact of Targeting β3 Receptor on Male Sex Hormonal Balance

Authors

  • Abdulla Ahmad Department of Clinical and Laboratory Sciences, College of Pharmacy, University of Mosul, Mosul, Iraq
  • Mohammed Saarti Department of Pharmacology and Toxicology, College of Pharmacy, University of Mosul, Mosul, Iraq
  • Mohammed Younes Department of Pharmacology and Toxicology, College of Pharmacy, University of Mosul, Mosul, Iraq

DOI:

https://doi.org/10.3889/oamjms.2022.10085

Keywords:

Estrogen, Progesterone, Testosterone, β3 receptor

Abstract

BACKGROUND:

Sympathetic stimulation has a significant impact on the physiology and pathology of the male reproductive system. β3 receptor is suspected to play a role in the regulation of fertility status in men.

AIM:

The study aims to investigate the role of the β3 receptor in regulating the fertility parameters (testosterone, estrogen, progesterone, and histology of testis) in male rats.

MATERIALS AND METHODS:

Male albino rats have been given either placebo (controls) or β3 agonist (Mirabegron). Testosterone, estrogen, and progesterone are measured before and after treatment for all cases and controls. Histology of testis is investigated for all the rats as well.

RESULTS:

β3 receptor activation caused a significant increase in testosterone plasma concentration and a significant reduction in estrogen plasma concentration. β3 agonist did not affect the progesterone plasma concentration. Histological sections showed that β3 activation resulted in degeneration of the spermatocytes and accumulation of edema between the seminiferous tubules in the testis.

CONCLUSION:

β3 receptor has a potentially important role in the fertility status of male rats via regulating sex hormonal profile and altering the histology of the testis.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Victor E, Osarugue I, Mega Obukohwo O, Eze Kingsley N, Alexander Obidike N. Endocrine functions of the testes. In: Male Reproductive Anatomy. London: IntechOpen; 2022. https://doi.org/10.5772/intechopen.101170

Mäkelä JA, Koskenniemi JJ, Virtanen HE, Toppari J. Testis development. Endocr Rev. 2019;40(4):857-905. https://doi.org/10.1210/er.2018-00140 PMid:30590466

O’Donnell L, Smith LB, Rebourcet D. Sertoli cells as key drivers of testis function. Semin Cell Dev Biol. 2022;121:2-9. https://doi.org/10.1016/j.semcdb.2021.06.016 PMid:34229950

França LR, Hess RA, Dufour JM, Hofmann MC, Griswold MD. The Sertoli cell: One hundred fifty years of beauty and plasticity. Andrology. 2016;4(2):189-212. https://doi.org/10.1111/andr.12165 PMid:26846984

Zirkin BR, Papadopoulos V. Leydig cells: Formation, function, and regulation. Biol Reprod. 2018;99(1):101-11. https://doi.org/10.1093/biolre/ioy059 PMid:29566165

De Miguel MP, Gonzalez-Peramato P, Nistal M. Morphological bases of human leydig cell dysfunction. In: Advances in Testosterone Action. London: IntechOpen; 2018. https://doi.org/10.5772/intechopen.79201

Patel DP, Chandrapal JC, Hotaling JM. Hormone-based treatments in subfertile males. Curr Urol Rep. 2016;17(8):56. https://doi.org/10.1007/s11934-016-0612-4 PMid:27292256

O’Hara L, Smith LB. Androgen receptor roles in spermatogenesis and infertility. Best Pract Res Clin Endocrinol Metab. 2015;29(5):595-605. https://doi.org/10.1016/j.beem.2015.04.006 PMid:26303086

Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Semin Cell Dev Biol. 2014;30:2-13. https://doi.org/10.1016/j.semcdb.2014.02.012 PMid:24598768

Di Guardo F, Vloeberghs V, Bardhi E, Blockeel C, Verheyen G, Tournaye H, et al. Low testosterone and semen parameters in male partners of infertile couples undergoing ivf with a total sperm count greater than 5 million. J Clin Med. 2020;9(12):3824. https://doi.org/10.3390/jcm9123824 PMid:33255908

Hamilton KJ, Hewitt SC, Arao Y, Korach KS. Estrogen hormone biology. Curr Top Dev Biol. 2017;125:109-46. https://doi.org/10.1016/bs.ctdb.2016.12.005 PMid:28527569

Filicori M. Clinical roles and applications of progesterone in reproductive medicine: An overview. Acta Obstet Gynecol Scand. 2015;94 Suppl 161:3-7. https://doi.org/10.1111/aogs.12791 PMid:26443945

Oettel M, Mukhopadhyay AK. Progesterone: The forgotten hormone in men? Aging Male. 2004;7(3):236-57. https://doi.org/10.1080/13685530400004199 PMid:15669543

Brodde OE. β1- and β2-Adrenoceptor polymorphisms and cardiovascular diseases. Fundam Clin Pharmacol. 2008;22(2):107-25. https://doi.org/10.1111/j.1472-8206.2007.00557.x PMid:18353108

Xanthopoulos A, Daskalopoulou I, Frountzi S, Papadimitriou E. A systematic review on the role of adrenergic receptors in angiogenesis regulation in health and disease. Int J Transl Med. 2021;1:353-65. https://doi.org/10.3390/ijtm1030021

Su L, Kopera-Sobota IA, Bilinska B, Cheng CY, Mruk DD. Germ cells contribute to the function of the Sertoli cell barrier. Spermatogenesis. 2013;3:e26460. https://doi.org/10.4161/spmg.26460

Troispoux C, Reiter E, Combarnous Y, Guillou F. β2 adrenergic receptors mediate cAMP, tissue-type p]asminogen activator and transferrin production in rat Sertoli cells. Mol Cell Endocrinol. 1998;142(1-2):75-86. https://doi.org/10.1016/s0303-7207(98)00115-4 PMid:9783905

Pointis G, Latreille MT. β-Adrenergic stimulation of androgen production by fetal mouse Leydig cells in primary culture. Experientia. 1986;42(6):617-9. https://doi.org/10.1007/bf01955560 PMid:2424782

Moger WH, Murphy PR. β-Adrenergic agonist induced androgen production during primary culture of mouse leydig cells. Arch Androl. 1983;10(2):135-42. https://doi.org/10.3109/01485018308987554 PMid:6134500

Ursino MG, Vasina V, Raschi E, Crema F, De Ponti F. The β3-adrenoceptor as a therapeutic target: Current perspectives. Pharmacol Res. 2009;59(4):221-34. https://doi.org/10.1016/j.phrs.2009.01.002 PMid:19429463

Michel LY, Farah C, Balligand JL. The beta3 adrenergic receptor in healthy and pathological cardiovascular tissues. Cells. 2020;9(12):2584. https://doi.org/10.3390/cells9122584 PMid:33276630

Sripad AA, Raker CA, Sung VW. Overactive bladder medication: Anticholinergics versus mirabegron by specialty. Urol J. 2022. https://doi.org/10.1177/03915603221076949 PMid:35195050

Cannavo A, Koch WJ. Targeting β3-adrenergic receptors in the heart: Selective agonism and β-blockade. J Cardiovasc Pharmacol. 2017;69(2):71-8. https://doi.org/10.1097/fjc.0000000000000444 PMid:28170359

Perrone MG, Scilimati A. β 3-Adrenoceptor agonists and (Antagonists as) inverse agonists. History, perspective, constitutive activity, and stereospecific binding. Methods Enzymol. 2010;484:197-230. https://doi.org/10.1016/b978-0-12-381298-8.00011-3 PMid:21036234

Valentine JM, Ahmadian M, Keinan O, Abu-Odeh M, Zhao P, Zhou X, et al. β3-Adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity. J Clin Invest. 2022;132(2):e153357. https://doi.org/10.1172/jci153357 PMid:34847077

Schena G, Caplan MJ. Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask). Cells. 2019;8:357. https://doi.org/10.3390/cells8040357 PMid:30995798

Michel MC, Ochodnicky P, Summers RJ. Tissue functions mediated by β 3-adrenoceptors - Findings and challenges. Naunyn Schmiedebergs Arch Pharmacol. 2010;382(2):103-8. https://doi.org/10.1007/s00210-010-0529-2 PMid:20517594

Elbaz R, El-Assmy A, Zahran MH, Hashem A, Shokeir AA. Mirabegron for treatment of erectile dysfunction concomitant with lower urinary tract symptoms in patients with benign prostatic obstruction: A randomized controlled trial. Int J Urol. 2022;29(5):390-6. https://doi.org/10.1111/iju.14792 PMid:35043484

Kurth F, Gaser C, Luders E. Development of sex differences in the human brain. Cogn Neurosci. 2021;12(3-4):155-62. https://doi.org/10.1080/17588928.2020.1800617 PMid:32902364

Shansky RM. Sex Differences in the Central Nervous System.1st Edition: Elsevier; 2015;1-414.

Giatti S, Diviccaro S, Serafini MM, Caruso D, Garcia- Segura LM, Viviani B, et al. Sex differences in steroid levels and steroidogenesis in the nervous system: Physiopathological role. Front Neuroendocrinol. 2020;56:100804. https://doi.org/10.1016/j.yfrne.2019.100804 PMid:31689419

Wolgemuth DJ, Laurion E, Lele KM. Regulation of the mitotic and meiotic cell cycles in the male germ line. Recent Prog Horm Res. 2002;57:75-101. https://doi.org/10.1210/rp.57.1.75 PMid:12017557

Sofikitis N, Giotitsas N, Tsounapi P, Baltogiannis D, Giannakis D, Pardalidis N. Hormonal regulation of spermatogenesis and spermiogenesis. J Steroid Biochem Mol Biol. 2008;109(3- 5):323-30. https://doi.org/10.1016/j.jsbmb.2008.03.004 PMid:18400489

Hasbi H, Gustina S. Androgen regulation in spermatogenesis to increase male fertility. Indonesian Bull Animal Vet Sci. 2018;28:13. https://doi.org/10.14334/wartazoa.v28i1.1643

Mhaouty-Kodja S, Lozach A, Habert R, Tanneux M, Guigon C, Brailly-Tabard S, et al. Fertility and spermatogenesis are altered in α1b-adrenergic receptor knockout male mice. J Endocrinol. 2007;195(2):281-92. https://doi.org/10.1677/joe-07-0071 PMid:17951539

Chen Y, Li H, Dong Q. Alpha1-adrenoceptor antagonists and ejaculation dysfunction. Zhonghua Nan Ke Xue. 2008;14(4):364-7. PMid:18481434

Lehtimäki J, Ventura-Aquino E, Chu X, Paredes RG, Ågmo A. Sexual incentive motivation and copulatory behavior in male rats treated with the adrenergic α2-adrenoceptor agonists tasipimidine and fadolmidine: Implications for treatment of premature ejaculation. J Sex Med. 2021;18(10):1677-89. https://doi.org/10.1016/j.jsxm.2021.07.010 PMid:34493465

Sanbe A, Tanaka Y, Fujiwara Y, Tsumura H, Yamauchi J, Cotecchia S, et al. α 1-Adrenoceptors are required for normal male sexual function. Br J Pharmacol. 2007;152(3):332-40. https://doi.org/10.1038/sj.bjp.0707366 PMid:17603545

Carbajal-García A, Reyes-García J, Montaño LM. Androgen effects on the adrenergic system of the vascular, airway, and cardiac myocytes and their relevance in pathological processes. Int J Endocrinol. 2020;2020:8849641. https://doi.org/10.1155/2020/8849641 PMid:33273918

Yuno K, Onishi Y, Arima A, Zaizen K, Aoki Y, Nakagawa S, et al. Effect of mirabegron on plasma gonadotropic and steroidal hormone levels in rats after two weeks of oral administration. J Toxicol Sci. 2014;39(3):507-14. https://doi.org/10.2131/jts.39.507 PMid:24849685

Kallner HK, Elmer C, Andersson KE, Altman D. Hormonal influence on the effect of mirabegron treatment for overactive bladder. Menopause. 2016;23(12):1303-6. https://doi.org/10.1097/gme.0000000000000708 PMid:27529461

Downloads

Published

2022-07-08

How to Cite

1.
Ahmad A, Saarti M, Younes M. Impact of Targeting β3 Receptor on Male Sex Hormonal Balance. Open Access Maced J Med Sci [Internet]. 2022 Jul. 8 [cited 2026 Oct. 19];10(A):1257-61. Available from: https://oamjms.eu/index.php/mjms/article/view/10085