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Androgen receptor levels and 5 alpha-reductase activities in preputial skin and chordee tissue of boys with isolated hypospadias.
J Urol. 1988 Nov; 140(5 Pt 2):1243-6.JU

Abstract

The cause of hypospadias in the majority of patients is unknown. We examined the hypothesis that hypospadias might be explained by androgen receptor abnormalities in the atretic spongiosal tissue commonly known as chordee. We studied 10 patients with relatively severe hypospadias but with a predominantly male phenotype and no readily ascertained explanation for the defect, including no evidence of an abnormality in testosterone biosynthesis. Eight subjects had midshaft hypospadias and 2 had a penoscrotal meatus. All 10 patients had severe chordee. Serum concentrations of testosterone, and luteinizing and follicle-stimulating hormones were measured before human chorionic gonadotropin stimulation and a serum testosterone level was determined 24 hours after the last dose of a 5-day human chorionic gonadotropin stimulation (3,000 units per M.2 per day). Androgen receptor content and binding affinity were assayed in fibroblasts cultured from preputial skin and chordee tissue of patients and foreskin from normal male neonates. With the endogenous ligand dihydrotestosterone the mean number (maximum binding capacity) of androgen receptors was 1,013 fmol. per mg. deoxyribonucleic acid in preputial skin and 833 fmol. per mg. deoxyribonucleic acid in chordee tissue of patients, and 627 fmol. per mg. deoxyribonucleic acid in the foreskin of controls. With the nonmetabolizable, synthetic androgen methyltrienolone (R1881) the mean maximum binding capacity was 1,004, 722 and 758 fmol. per mg. deoxyribonucleic acid, respectively. Dihydrotestosterone receptor affinity (dissociation constant) was similar in preputial skin (0.20 nM.) and chordee tissue (0.21 nM.) from patients, and foreskin (0.29 nM.) from controls. Androgen receptor binding affinity of R1881 also was similar (0.30, 0.24 and 0.21 nM., respectively). Furthermore, the 5 alpha-reductase activity of preputial skin and chordee tissue of patients with hypospadias was similar to that of foreskin from normal neonates. In conclusion, isolated hypospadias in these subjects was not associated with androgen insensitivity of the spongiosal tissues on the basis of either decreased androgen receptor binding affinity, receptor number or conversion of testosterone to dihydrotestosterone.

Authors+Show Affiliations

James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

3263511

Citation

Gearhart, J P., et al. "Androgen Receptor Levels and 5 Alpha-reductase Activities in Preputial Skin and Chordee Tissue of Boys With Isolated Hypospadias." The Journal of Urology, vol. 140, no. 5 Pt 2, 1988, pp. 1243-6.
Gearhart JP, Linhard HR, Berkovitz GD, et al. Androgen receptor levels and 5 alpha-reductase activities in preputial skin and chordee tissue of boys with isolated hypospadias. J Urol. 1988;140(5 Pt 2):1243-6.
Gearhart, J. P., Linhard, H. R., Berkovitz, G. D., Jeffs, R. D., & Brown, T. R. (1988). Androgen receptor levels and 5 alpha-reductase activities in preputial skin and chordee tissue of boys with isolated hypospadias. The Journal of Urology, 140(5 Pt 2), 1243-6.
Gearhart JP, et al. Androgen Receptor Levels and 5 Alpha-reductase Activities in Preputial Skin and Chordee Tissue of Boys With Isolated Hypospadias. J Urol. 1988;140(5 Pt 2):1243-6. PubMed PMID: 3263511.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Androgen receptor levels and 5 alpha-reductase activities in preputial skin and chordee tissue of boys with isolated hypospadias. AU - Gearhart,J P, AU - Linhard,H R, AU - Berkovitz,G D, AU - Jeffs,R D, AU - Brown,T R, PY - 1988/11/1/pubmed PY - 1988/11/1/medline PY - 1988/11/1/entrez SP - 1243 EP - 6 JF - The Journal of urology JO - J. Urol. VL - 140 IS - 5 Pt 2 N2 - The cause of hypospadias in the majority of patients is unknown. We examined the hypothesis that hypospadias might be explained by androgen receptor abnormalities in the atretic spongiosal tissue commonly known as chordee. We studied 10 patients with relatively severe hypospadias but with a predominantly male phenotype and no readily ascertained explanation for the defect, including no evidence of an abnormality in testosterone biosynthesis. Eight subjects had midshaft hypospadias and 2 had a penoscrotal meatus. All 10 patients had severe chordee. Serum concentrations of testosterone, and luteinizing and follicle-stimulating hormones were measured before human chorionic gonadotropin stimulation and a serum testosterone level was determined 24 hours after the last dose of a 5-day human chorionic gonadotropin stimulation (3,000 units per M.2 per day). Androgen receptor content and binding affinity were assayed in fibroblasts cultured from preputial skin and chordee tissue of patients and foreskin from normal male neonates. With the endogenous ligand dihydrotestosterone the mean number (maximum binding capacity) of androgen receptors was 1,013 fmol. per mg. deoxyribonucleic acid in preputial skin and 833 fmol. per mg. deoxyribonucleic acid in chordee tissue of patients, and 627 fmol. per mg. deoxyribonucleic acid in the foreskin of controls. With the nonmetabolizable, synthetic androgen methyltrienolone (R1881) the mean maximum binding capacity was 1,004, 722 and 758 fmol. per mg. deoxyribonucleic acid, respectively. Dihydrotestosterone receptor affinity (dissociation constant) was similar in preputial skin (0.20 nM.) and chordee tissue (0.21 nM.) from patients, and foreskin (0.29 nM.) from controls. Androgen receptor binding affinity of R1881 also was similar (0.30, 0.24 and 0.21 nM., respectively). Furthermore, the 5 alpha-reductase activity of preputial skin and chordee tissue of patients with hypospadias was similar to that of foreskin from normal neonates. In conclusion, isolated hypospadias in these subjects was not associated with androgen insensitivity of the spongiosal tissues on the basis of either decreased androgen receptor binding affinity, receptor number or conversion of testosterone to dihydrotestosterone. SN - 0022-5347 UR - https://www.unboundmedicine.com/medline/citation/3263511/Androgen_receptor_levels_and_5_alpha_reductase_activities_in_preputial_skin_and_chordee_tissue_of_boys_with_isolated_hypospadias_ L2 - https://www.jurology.com/doi/full/10.1016/s0022-5347(17)42014-3?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -