Effects of sex hormones on vascular reactivity in boys with hypospadias

Lucas-Herald, A. K. et al. (2023) Effects of sex hormones on vascular reactivity in boys with hypospadias. Journal of Clinical Endocrinology and Metabolism, (doi: 10.1210/clinem/dgad525) (PMID:37672642) (Early Online Publication)

Abstract

Background: Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear. Aims: We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias. Methods: Excess foreskin tissue was obtained from 11 boys undergoing hypospadias repair (cases) and 12 undergoing routine circumcision (controls) (median age [range], 1.5 [1.2-2.7] years) and small resistance arteries were isolated. Vessels were mounted on wire myographs and vascular reactivity was assessed in the absence/presence of 17β-estradiol, dihydrotestosterone (DHT), and testosterone. Results: In controls, testosterone and 17β-estradiol increased contraction (percent of maximum contraction [Emax]: 83.74 basal vs 125.4 after testosterone, P < .0002; and 83.74 vs 110.2 after estradiol, P = .02). 17β-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine, P < .0001; and Emax: 14.6 vs 20.5 to sodium nitroprusside, P < .0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, P = .01) and 17β-estradiol (Emax: 156.9 vs 23.6, P < .0001) reduced contraction. Androgens, but not 17β-estradiol, increased endothelium-dependent and endothelium-independent vasorelaxation in cases (Emax: 77.3 vs 51.7 with testosterone, P = .02; and vs 48.2 with DHT to acetylcholine, P = .0001; Emax: 43.0 vs 39.5 with testosterone, P = .02; and 39.6 vs 37.5 with DHT to sodium nitroprusside, P = .04). Conclusion: In healthy boys, testosterone and 17β-estradiol promote a vasoconstrictor phenotype, whereas in boys with hypospadias, these sex hormones reduce vasoconstriction, with androgens promoting vasorelaxation. Differences in baseline artery function may therefore be sex hormone-independent and the impact of early-life variations in androgen exposure on vascular function needs further study.

• Item Type: Articles
• Status: Early Online Publication
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Lee, Ms Boma and Brooksbank, Dr Katriona and O'Toole, Mr Stuart and Mcneilly, Dr Jane and Haddow, Mrs Laura and Alves Moreira Lopes, Dr Rheure and Ahmed, Professor Syed Faisal and Steven, Miss Mairi and Montezano, Dr Augusto and Flett, Mr Martyn and Lucas-Herald, Dr Angela and Touyz, Professor Rhian
• Authors: Lucas-Herald, A. K., Montezano, A. C., Alves-Lopes, R., Haddow, L., O'Toole, S., Flett, M., Lee, B., Amjad, S. B., Steven, M., McNeilly, J., Brooksbank, K., Touyz, R. M., and Ahmed, S. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of Clinical Endocrinology and Metabolism
• Publisher: Oxford University Press
• ISSN: 0021-972X
• ISSN (Online): 1945-7197
• Published Online: 06 September 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Journal of Clinical Endocrinology and Metabolism 2023
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190814		BHF centre of excellence	Rhian Touyz	British Heart Foundation (BHF)	RE/13/5/30177	School of Cardiovascular & Metabolic Health
303944		BHF Centre of Excellence	Colin Berry	British Heart Foundation (BHF)	RE/18/6/34217	SCMH - Cardiovascular & Metabolic Health
300689		Vascular Noxs as therapeutic targets and biomarkers in hypertension	Rhian Touyz	British Heart Foundation (BHF)	CH/12/4/29762	SCMH - Cardiovascular & Metabolic Health