The Impact of Levothyroxine and Testosterone Administration on Bladder Contractility in the Rat Model of Propylthiouracil-Induced Hypothyroidism

Overview

Journal Urol Res Pract

Date 2025 Jan 28

PMID 39873473

Authors

Didem Yilmaz Oral

Berna Guven Ciloglu

Serap Gur

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the effects of testosterone (T) treatment, with or without levothyroxine, the most widely used and least effective medication for managing hypothyroidism, on the functional and histological changes in propylthiouracil (PTU)- induced hypothyroid rat bladders.

Methods: Male rats (n=35) were split into control, hypothyroid, hypothyroid rats treated with levothyroxine (20 µg/kg/day, oral, 2-weeks), hypothyroid rats treated with Sustanon (10 mg/kg,iIM, once/week, 2-weeks), and hypothyroid rats treated with combined treatment groups. Hypothyroidism was induced by PTU (0.05% in drinking water, 6 weeks). The serum concentration of triiodothyronine (T3), thyroxine (T4), total T, and the detrusor muscle's contractile responses were determined. A morphological study was conducted using Masson trichrome staining.

Results: Triiodothyronine, T4, and T levels were considerably reduced in rats with hypothyroidism; however, these hormones were restored by levothyroxine and Sustanon. Compared to controls, the combination therapy improved the ratio of smooth muscle to collagen and the contractile responses to carbachol, electrical field stimulation, and adenosine triphosphate in the hypothyroid bladder.

Conclusion: The authors' research suggests that hypothyroidism may affect the contractility and morphology of the bladder. In males with hypothyroidism and urogenital system dysfunction, combination therapy with thyroid hormones and T has a major impact on repairing detrusor smooth muscle contractility and bladder histomorphology.

References

Abdel-Hamid A, Ali E . Effect of testosterone therapy on the urinary bladder in experimental hypogonadism of rats. J Mol Histol. 2015; 46(3):263-72. DOI: 10.1007/s10735-015-9617-4. View

Andersen L, Agner T, Walter S, Hansen J . Micturition pattern in hyperthyroidism and hypothyroidism. Urology. 1987; 29(2):223-4. DOI: 10.1016/0090-4295(87)90161-0. View

M E Hess , Barasha B, Winters S, Levin R . Effect of thyroxine on urinary bladder autonomic receptor densities and contractility. Pharmacology. 1993; 46(5):248-53. DOI: 10.1159/000139052. View

Bruno A, Diniz G, Ricachenevsky F, Pochmann D, Bonan C, Barreto-Chaves M . Hypo-and hyperthyroidism affect the ATP, ADP and AMP hydrolysis in rat hippocampal and cortical slices. Neurosci Res. 2005; 52(1):61-8. DOI: 10.1016/j.neures.2005.01.009. View

Cooper D, Biondi B . Subclinical thyroid disease. Lancet. 2012; 379(9821):1142-54. DOI: 10.1016/S0140-6736(11)60276-6. View

Pan T, Zhong M, Zhong X, Zhang Y, Zhu D . Levothyroxine replacement therapy with vitamin E supplementation prevents oxidative stress and cognitive deficit in experimental hypothyroidism. Endocrine. 2012; 43(2):434-9. DOI: 10.1007/s12020-012-9801-1. View

Zargham M, Hajian M, Alizadeh F, Eslami M, Khalili Boroujeni N, Gholipour F . Hypothyroidism is prevalent among adult women with chronic lower urinary tract symptoms. Low Urin Tract Symptoms. 2022; 14(4):248-254. DOI: 10.1111/luts.12428. View

Takyu S . [Effects of testosterone on the autonomic receptor-mediated function in lower urinary tract from male rabbits]. Nihon Hinyokika Gakkai Zasshi. 1993; 84(2):330-8. DOI: 10.5980/jpnjurol1989.84.330. View

Gilani N, Wang K, Muncan A, Peter J, An S, Bhatti S . Triiodothyronine maintains cardiac transverse-tubule structure and function. J Mol Cell Cardiol. 2021; 160:1-14. PMC: 8570994. DOI: 10.1016/j.yjmcc.2021.06.010. View

10.

Magari T, Shibata Y, Arai S, Kashiwagi B, Suzuki K, Suzuki K . Time-dependent effects of castration on the bladder function and histological changes in the bladder and blood vessels. Asian J Androl. 2014; 16(3):457-60. PMC: 4023378. DOI: 10.4103/1008-682X.123676. View

11.

Hansen M, Engberg A . Uremia as a complication to urinary retention due to hypothyreosis. Case report. Scand J Urol Nephrol. 1988; 22(4):351-3. DOI: 10.3109/00365598809180814. View

12.

Adeniyi K, Ogunkeye O, Senok S, Udoh F . Influence of the thyroid state on the intrinsic contractile properties of the bladder muscle. Acta Physiol Hung. 1994; 82(1):69-74. View

13.

Tek M, Balli E, Cimen B, Efesoy O, Oguz I, Cayan S . The effect of testosterone replacement therapy on bladder functions and histology in orchiectomized mature male rats. Urology. 2009; 75(4):886-90. DOI: 10.1016/j.urology.2009.08.016. View

14.

Bruno A, Carneiro-Ramos M, Buffon A, Pochmann D, Ricachenevsky F, Barreto-Chaves M . Thyroid hormones alter the adenine nucleotide hydrolysis in adult rat blood serum. Biofactors. 2011; 37(1):40-5. DOI: 10.1002/biof.133. View

15.

Kaya-Sezginer E, Yilmaz-Oral D, Gur S . Administration of human umbilical cord blood mononuclear cells restores bladder dysfunction in streptozotocin-induced diabetic rats. Low Urin Tract Symptoms. 2019; 11(4):232-240. DOI: 10.1111/luts.12268. View

16.

Badavi M, Grootveld M, Jafari F, Dianat M, Faraji Shahrivar F . Supplement therapy with apelin for improving the TSH level and lipid disorders in PTU-induced hypothyroid rats. Biotechnol Appl Biochem. 2021; 69(2):668-675. DOI: 10.1002/bab.2142. View

17.

Sanchez-Garcia O, Lopez-Juarez R, Rodriguez-Castelan J, Corona-Quintanilla D, Martinez-Gomez M, Cuevas-Romero E . Hypothyroidism impairs somatovisceral reflexes involved in micturition of female rabbits. Neurourol Urodyn. 2018; 37(8):2406-2413. DOI: 10.1002/nau.23594. View

18.

MENDEZ BAUER C, Caldeyro-Barcia R, De Angelis R, MAGGIOLO J, POU-DE-SANTIAGO A, MUSSIO FOURNIER J . Effect of thyroid therapy on the tone and contractility of the urinary bladder in hypothyroidism. J Clin Endocrinol Metab. 1957; 17(7):884-8. DOI: 10.1210/jcem-17-7-884. View

19.

Gabrielson A, Sartor R, Hellstrom W . The Impact of Thyroid Disease on Sexual Dysfunction in Men and Women. Sex Med Rev. 2018; 7(1):57-70. DOI: 10.1016/j.sxmr.2018.05.002. View

20.

Nathan A, Havard C . Paralytic ileus and urinary retention due to hypothyroidism. Br Med J (Clin Res Ed). 1982; 285(6340):477. PMC: 1499278. DOI: 10.1136/bmj.285.6340.477. View