PMID- 15181062
OWN - NLM
STAT- MEDLINE
DCOM- 20040719
LR  - 20161124
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 89
IP  - 6
DP  - 2004 Jun
TI  - Lack of defects in androgen production in children with hypospadias.
PG  - 2811-6
AB  - Formation of the male urethra requires the synthesis of testosterone, its 
      activation to dihydrotestosterone (DHT) in genital skin, and binding of DHT to 
      the androgen receptor. Defects in any of those steps can cause hypospadias. To 
      determine whether defects exist in the production of androgens in individuals 
      with hypospadias, we examined enzymatic function of 3beta-hydroxysteroid 
      dehydrogenase (3betaHSD), P450c17 (17alpha-hydroxylase and 17,20 lyase activity), 
      and type 3 17betaHSD. Sixty-eight subjects participated in the study: 48 patients 
      had hypospadias, and 20 had normal male genitalia. Subjects were stratified into 
      groups based on age and severity of hypospadias, as defined by location of the 
      urethral meatus after correction of penile curvature. Hormonal values in boys 
      with hypospadias were compared by nonparametric analysis with those in 
      age-matched controls. Controls excluded individuals with cryptorchidism, 
      micropenis, known endocrine defects, or receiving steroid supplementation. 
      Morning fasting serum levels of pregnenolone, progesterone, 
      11-deoxycorticosterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 
      11-deoxycortisol, cortisol, dehydroepiandrosterone, androstenedione, 
      androstenediol, testosterone, and DHT were determined. To focus on the proximal 
      steps in androgen biosynthesis, 12 individuals with hypospadias underwent 
      standard ACTH stimulation. No significant differences in the androgen precursors 
      and metabolites were found between controls and individuals with hypospadias. The 
      response to ACTH was variable without a significant difference between the 
      patients with different degrees of hypospadias and/or published controls. These 
      data indicate that enzymatic defects in the steroidogenic steps from cholesterol 
      to DHT are not a common etiology of hypospadias. Routine abnormalities in the 
      androgen biosynthetic pathway are an unlikely cause of any degree of hypospadias 
      in boys without accompanying cryptorchidism or genital malformations.
FAU - Holmes, Nicholas M
AU  - Holmes NM
AD  - Department of Urology, University of California, San Francisco, California 94143, 
      USA.
FAU - Miller, Walter L
AU  - Miller WL
FAU - Baskin, Laurence S
AU  - Baskin LS
LA  - eng
GR  - DK-058105/DK/NIDDK NIH HHS/United States
GR  - HD/DK-41958/HD/NICHD NIH HHS/United States
GR  - M01-RR-01271/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Androgens)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 1.1.- (3-Hydroxysteroid Dehydrogenases)
RN  - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 3-Hydroxysteroid Dehydrogenases/metabolism
MH  - Adrenocorticotropic Hormone/blood
MH  - Androgens/biosynthesis/*blood
MH  - Cholesterol/metabolism
MH  - Humans
MH  - Hydrocortisone/blood
MH  - Hypospadias/*metabolism
MH  - Infant
MH  - Male
MH  - Steroid 17-alpha-Hydroxylase/metabolism
EDAT- 2004/06/08 05:00
MHDA- 2004/07/20 05:00
CRDT- 2004/06/08 05:00
PHST- 2004/06/08 05:00 [pubmed]
PHST- 2004/07/20 05:00 [medline]
PHST- 2004/06/08 05:00 [entrez]
AID - 89/6/2811 [pii]
AID - 10.1210/jc.2003-032098 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2004 Jun;89(6):2811-6. doi: 10.1210/jc.2003-032098.