Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias

被引:0
作者
Lucas-Herald, Angela K. [1 ,2 ]
Montezano, Augusto C. [1 ,3 ]
Alves-Lopes, Rheure [1 ]
Haddow, Laura [1 ]
O'Toole, Stuart [4 ]
Flett, Martyn [4 ]
Lee, Boma [4 ]
Amjad, S. Basith [4 ]
Steven, Mairi [4 ]
McNeilly, Jane [2 ,5 ]
Brooksbank, Katriona [1 ]
Touyz, Rhian M. [1 ,3 ]
Ahmed, S. Faisal [2 ,6 ]
机构
[1] Univ Glasgow, British Heart Fdn Ctr Res Excellence, Inst Cardiovasc & Med Sci, 126 Univ Ave, Glasgow G12 8TA, Scotland
[2] Univ Glasgow, Royal Hosp Children, Sch Med Dent & Nursing, Dev Endocrinol Res Grp, 1345 Govan Rd, Glasgow G51 4TF, Scotland
[3] McGill Univ, Res Inst, Hlth Ctr, 1001 Boul Decarie, Montreal, PQ H4A 3J1, Canada
[4] Royal Hosp Children, Dept Pediat Surg, 1345 Govan Rd, Glasgow G51 4TF, Scotland
[5] Queen Elizabeth Univ Hosp, Dept Clin Biochem, Glasgow G51 4TF, Scotland
[6] Univ Glasgow, Royal Hosp Children, Sch Med Dent & Nursing, Dev Endocrinol Res Grp, Off Block,1345 Govan Rd, Glasgow City G51 4TF, Scotland
关键词
testosterone; vessel; estrogen; dihydrotestosterone; androgen; ESTROGEN-RECEPTOR-ALPHA; GENETIC POLYMORPHISMS; PROGRAMMING WINDOW; ESR1; GENE; TESTOSTERONE; MASCULINIZATION; EXPRESSION; ANDROGENS; CELLS; RISK;
D O I
10.1210/clinem/dgad525
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 17 beta-estradiol, dihydrotestosterone (DHT), and testosterone. Results :In controls, testosterone and 17 beta-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). 17 beta-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 17 beta-estradiol (Emax: 156.9 vs 23.6, P < .0001) reduced contraction. Androgens, but not 17 beta-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 17 beta-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.
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收藏
页码:e735 / e744
页数:10
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