Effects of sex hormones on vascular reactivity in boys with hypospadias.
Testosterone
androgen
dihydrotestosterone
estrogen
vessel
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
06 Sep 2023
06 Sep 2023
Historique:
received:
11
01
2023
revised:
23
08
2023
accepted:
31
08
2023
medline:
6
9
2023
pubmed:
6
9
2023
entrez:
6
9
2023
Statut:
aheadofprint
Résumé
Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear. We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias. 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) yrs) 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. In controls, testosterone and 17β-estradiol increased contraction (Emax: 83.74 basal vs 125.4 after testosterone, p < 0.0002 and 83.74 vs 110.2 after estradiol, p = 0.02). 17β-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine (ACh), p < 0.0001 and Emax: 14.6 vs 20.5 to sodium nitroprusside (SNP), p < 0.0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, p = 0.01) and 17β-estradiol (Emax: 156.9 vs 23.6, p < 0.0001) 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 = 0.02 and vs 48.2 with DHT to ACh, p = 0.0001; Emax: 43.0 vs 39.5 with testosterone, p = 0.02 and vs 39.6 vs 37.5 with DHT to SNP, p = 0.04). 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.
Sections du résumé
BACKGROUND
BACKGROUND
Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear.
AIMS
OBJECTIVE
We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias.
METHODS
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) yrs) 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
RESULTS
In controls, testosterone and 17β-estradiol increased contraction (Emax: 83.74 basal vs 125.4 after testosterone, p < 0.0002 and 83.74 vs 110.2 after estradiol, p = 0.02). 17β-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine (ACh), p < 0.0001 and Emax: 14.6 vs 20.5 to sodium nitroprusside (SNP), p < 0.0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, p = 0.01) and 17β-estradiol (Emax: 156.9 vs 23.6, p < 0.0001) 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 = 0.02 and vs 48.2 with DHT to ACh, p = 0.0001; Emax: 43.0 vs 39.5 with testosterone, p = 0.02 and vs 39.6 vs 37.5 with DHT to SNP, p = 0.04).
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 37672642
pii: 7261683
doi: 10.1210/clinem/dgad525
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : British Heart Foundation
ID : CH/12/4/29762
Pays : United Kingdom
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.