The relationship between Müllerian inhibiting substance and androgens in boys with hypospadias

Paul F. Austin, Yong Siow, Mary E. Fallat, Mark P. Cain, Richard C. Rink, Anthony J. Casale, Ian Aaronson, Antoine Khoury, Steve Zderic

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: The etiology of hypospadias is probably multifactorial and disruption of androgen production may have a role. Müllerian inhibiting substance (MIS), a hormone produced by Sertoli cells, has been shown to suppress androgen biosynthesis in Leydig cells by inhibiting cytochrome P450c17 hydroxylase/lyase (CYP17) gene expression. We investigated the relationship between serum MIS and androgens in boys with isolated hypospadias compared with normal boys. Materials and Methods: Serum levels of MIS, testosterone and androstenedione were measured in 29 boys with distal hypospadias (midshaft or less) and 21 normal boys undergoing circumcision. The subjects were stratified according to age 12 months or younger (group 1) and 13 to 24 months old (group 2). Statistical evaluation was performed by Student's t test. Results: Mean age plus or minus standard error of mean of normal boys and their respective age matched groups with hypospadias were not significantly different. Within each respective age group serum müllerian inhibiting substance levels in boys with hypospadias were significantly higher compared with those of normal boys (129.6 ± 1.8 and 96.1 ± 1.8, p <0.03 for group 1 and 143.2 ± 2.0 and 77.2 ± 2.3, p <0.005 for group 2). Serum MIS levels were not statistically different when normal boys or boys with hypospadias were compared across age groups. In group 1 serum testosterone levels in boys with hypospadias were not significantly different from those of normal boys (0.36 ± 0.20 and 0.56 ± 0.32 pg./ml., respectively). In group 2 normal boys serum testosterone levels were higher than these in boys with hypospadias (2.36 ± 0.47 and 0.35 ± 0.23 pg./ml., p <0.01). Serum androstenedione levels in group 1 boys with hypospadias were significantly lower compared with those of normal boys of similar age (0.29 ± 0.1 and 0.64 ± 0.16 ng./ml., respectively, p <0.003). Androstenedione levels among older boys were not different (0.49 ± 0.25 and 0.32 ± 0.11 ng./ml., respectively. Conclusions: The association between elevated serum MIS levels and lower testosterone concentrations in boys with hypospadias suggests that MIS may have some role in the development of hypospadias, possibly mediated by MIS inhibition of CYP17 gene expression.

Original languageEnglish (US)
Pages (from-to)1784-1788
Number of pages5
JournalJournal of Urology
Volume168
Issue number4 II
StatePublished - Oct 2002
Externally publishedYes

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Hypospadias
Androgens
Serum
Androstenedione
Testosterone
Lyases
Age Groups
Cytochromes
Mixed Function Oxygenases
Gene Expression
Leydig Cells
Sertoli Cells

Keywords

  • Hypospadias
  • Müllerian Ducts
  • Testosterone

ASJC Scopus subject areas

  • Urology

Cite this

Austin, P. F., Siow, Y., Fallat, M. E., Cain, M. P., Rink, R. C., Casale, A. J., ... Zderic, S. (2002). The relationship between Müllerian inhibiting substance and androgens in boys with hypospadias. Journal of Urology, 168(4 II), 1784-1788.

The relationship between Müllerian inhibiting substance and androgens in boys with hypospadias. / Austin, Paul F.; Siow, Yong; Fallat, Mary E.; Cain, Mark P.; Rink, Richard C.; Casale, Anthony J.; Aaronson, Ian; Khoury, Antoine; Zderic, Steve.

In: Journal of Urology, Vol. 168, No. 4 II, 10.2002, p. 1784-1788.

Research output: Contribution to journalArticle

Austin, PF, Siow, Y, Fallat, ME, Cain, MP, Rink, RC, Casale, AJ, Aaronson, I, Khoury, A & Zderic, S 2002, 'The relationship between Müllerian inhibiting substance and androgens in boys with hypospadias', Journal of Urology, vol. 168, no. 4 II, pp. 1784-1788.
Austin PF, Siow Y, Fallat ME, Cain MP, Rink RC, Casale AJ et al. The relationship between Müllerian inhibiting substance and androgens in boys with hypospadias. Journal of Urology. 2002 Oct;168(4 II):1784-1788.
Austin, Paul F. ; Siow, Yong ; Fallat, Mary E. ; Cain, Mark P. ; Rink, Richard C. ; Casale, Anthony J. ; Aaronson, Ian ; Khoury, Antoine ; Zderic, Steve. / The relationship between Müllerian inhibiting substance and androgens in boys with hypospadias. In: Journal of Urology. 2002 ; Vol. 168, No. 4 II. pp. 1784-1788.
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abstract = "Purpose: The etiology of hypospadias is probably multifactorial and disruption of androgen production may have a role. M{\"u}llerian inhibiting substance (MIS), a hormone produced by Sertoli cells, has been shown to suppress androgen biosynthesis in Leydig cells by inhibiting cytochrome P450c17 hydroxylase/lyase (CYP17) gene expression. We investigated the relationship between serum MIS and androgens in boys with isolated hypospadias compared with normal boys. Materials and Methods: Serum levels of MIS, testosterone and androstenedione were measured in 29 boys with distal hypospadias (midshaft or less) and 21 normal boys undergoing circumcision. The subjects were stratified according to age 12 months or younger (group 1) and 13 to 24 months old (group 2). Statistical evaluation was performed by Student's t test. Results: Mean age plus or minus standard error of mean of normal boys and their respective age matched groups with hypospadias were not significantly different. Within each respective age group serum m{\"u}llerian inhibiting substance levels in boys with hypospadias were significantly higher compared with those of normal boys (129.6 ± 1.8 and 96.1 ± 1.8, p <0.03 for group 1 and 143.2 ± 2.0 and 77.2 ± 2.3, p <0.005 for group 2). Serum MIS levels were not statistically different when normal boys or boys with hypospadias were compared across age groups. In group 1 serum testosterone levels in boys with hypospadias were not significantly different from those of normal boys (0.36 ± 0.20 and 0.56 ± 0.32 pg./ml., respectively). In group 2 normal boys serum testosterone levels were higher than these in boys with hypospadias (2.36 ± 0.47 and 0.35 ± 0.23 pg./ml., p <0.01). Serum androstenedione levels in group 1 boys with hypospadias were significantly lower compared with those of normal boys of similar age (0.29 ± 0.1 and 0.64 ± 0.16 ng./ml., respectively, p <0.003). Androstenedione levels among older boys were not different (0.49 ± 0.25 and 0.32 ± 0.11 ng./ml., respectively. Conclusions: The association between elevated serum MIS levels and lower testosterone concentrations in boys with hypospadias suggests that MIS may have some role in the development of hypospadias, possibly mediated by MIS inhibition of CYP17 gene expression.",
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T1 - The relationship between Müllerian inhibiting substance and androgens in boys with hypospadias

AU - Austin, Paul F.

AU - Siow, Yong

AU - Fallat, Mary E.

AU - Cain, Mark P.

AU - Rink, Richard C.

AU - Casale, Anthony J.

AU - Aaronson, Ian

AU - Khoury, Antoine

AU - Zderic, Steve

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N2 - Purpose: The etiology of hypospadias is probably multifactorial and disruption of androgen production may have a role. Müllerian inhibiting substance (MIS), a hormone produced by Sertoli cells, has been shown to suppress androgen biosynthesis in Leydig cells by inhibiting cytochrome P450c17 hydroxylase/lyase (CYP17) gene expression. We investigated the relationship between serum MIS and androgens in boys with isolated hypospadias compared with normal boys. Materials and Methods: Serum levels of MIS, testosterone and androstenedione were measured in 29 boys with distal hypospadias (midshaft or less) and 21 normal boys undergoing circumcision. The subjects were stratified according to age 12 months or younger (group 1) and 13 to 24 months old (group 2). Statistical evaluation was performed by Student's t test. Results: Mean age plus or minus standard error of mean of normal boys and their respective age matched groups with hypospadias were not significantly different. Within each respective age group serum müllerian inhibiting substance levels in boys with hypospadias were significantly higher compared with those of normal boys (129.6 ± 1.8 and 96.1 ± 1.8, p <0.03 for group 1 and 143.2 ± 2.0 and 77.2 ± 2.3, p <0.005 for group 2). Serum MIS levels were not statistically different when normal boys or boys with hypospadias were compared across age groups. In group 1 serum testosterone levels in boys with hypospadias were not significantly different from those of normal boys (0.36 ± 0.20 and 0.56 ± 0.32 pg./ml., respectively). In group 2 normal boys serum testosterone levels were higher than these in boys with hypospadias (2.36 ± 0.47 and 0.35 ± 0.23 pg./ml., p <0.01). Serum androstenedione levels in group 1 boys with hypospadias were significantly lower compared with those of normal boys of similar age (0.29 ± 0.1 and 0.64 ± 0.16 ng./ml., respectively, p <0.003). Androstenedione levels among older boys were not different (0.49 ± 0.25 and 0.32 ± 0.11 ng./ml., respectively. Conclusions: The association between elevated serum MIS levels and lower testosterone concentrations in boys with hypospadias suggests that MIS may have some role in the development of hypospadias, possibly mediated by MIS inhibition of CYP17 gene expression.

AB - Purpose: The etiology of hypospadias is probably multifactorial and disruption of androgen production may have a role. Müllerian inhibiting substance (MIS), a hormone produced by Sertoli cells, has been shown to suppress androgen biosynthesis in Leydig cells by inhibiting cytochrome P450c17 hydroxylase/lyase (CYP17) gene expression. We investigated the relationship between serum MIS and androgens in boys with isolated hypospadias compared with normal boys. Materials and Methods: Serum levels of MIS, testosterone and androstenedione were measured in 29 boys with distal hypospadias (midshaft or less) and 21 normal boys undergoing circumcision. The subjects were stratified according to age 12 months or younger (group 1) and 13 to 24 months old (group 2). Statistical evaluation was performed by Student's t test. Results: Mean age plus or minus standard error of mean of normal boys and their respective age matched groups with hypospadias were not significantly different. Within each respective age group serum müllerian inhibiting substance levels in boys with hypospadias were significantly higher compared with those of normal boys (129.6 ± 1.8 and 96.1 ± 1.8, p <0.03 for group 1 and 143.2 ± 2.0 and 77.2 ± 2.3, p <0.005 for group 2). Serum MIS levels were not statistically different when normal boys or boys with hypospadias were compared across age groups. In group 1 serum testosterone levels in boys with hypospadias were not significantly different from those of normal boys (0.36 ± 0.20 and 0.56 ± 0.32 pg./ml., respectively). In group 2 normal boys serum testosterone levels were higher than these in boys with hypospadias (2.36 ± 0.47 and 0.35 ± 0.23 pg./ml., p <0.01). Serum androstenedione levels in group 1 boys with hypospadias were significantly lower compared with those of normal boys of similar age (0.29 ± 0.1 and 0.64 ± 0.16 ng./ml., respectively, p <0.003). Androstenedione levels among older boys were not different (0.49 ± 0.25 and 0.32 ± 0.11 ng./ml., respectively. Conclusions: The association between elevated serum MIS levels and lower testosterone concentrations in boys with hypospadias suggests that MIS may have some role in the development of hypospadias, possibly mediated by MIS inhibition of CYP17 gene expression.

KW - Hypospadias

KW - Müllerian Ducts

KW - Testosterone

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