TY - JOUR
T1 - Steroid 5α-reductase 1 promotes 5α-androstane-3α, 17β-diol synthesis in immature mouse testes by two pathways
AU - Mahendroo, Mala
AU - Wilson, Jean D.
AU - Richardson, James A.
AU - Auchus, Richard J.
N1 - Funding Information:
This work was aided by Grant 0203 from the Burroughs Wellcome Fund (MM) and Grant R21DK59942 from the National Institutes of Health (RJA). We thank John M. Shelton for assistance with the in situ hybridization studies, Michael J. McPhaul for use of his laboratory, and Judith A. Gruber, Jacob D. Villegas, and Tara L. Billman for able technical assistance.
PY - 2004/7/30
Y1 - 2004/7/30
N2 - 5α-Androstane-3α,17β-diol (androstanediol) is the predominant androgen in immature mouse testes, and studies were designed to investigate its pathway of synthesis, the steroid 5α-reductase isoenzyme involved in its formation, and whether testicular androstanediol is formed in embryonic mouse testes at the time of male phenotypic development. In 24-26-day-old immature testes, androstanediol is formed by two pathways; the predominant one involves testosterone → dihydrotestosterone → androstanediol, and a second utilizes the pathway progesterone → 5α-dihydroprogesterone → 5α-pregnane-3α-ol-20-one → 5α-pregnane-3α,17α-diol-20-one → androsterone → androstanediol. Formation of androstanediol was normal in testes from mice deficient in steroid 5α-reductase 2 but absent in testes from mice deficient in steroid 5α-reductase 1, indicating that isoenzyme 2 is not expressed in day 24-26 testes. The fact that androstenedione and testosterone were the only androgens identified after incubation of day 16 and 17 embryonic testes with [3H]progesterone implies that androstanediol formation in the testis plays no role in male phenotypic differentiation in the mouse.
AB - 5α-Androstane-3α,17β-diol (androstanediol) is the predominant androgen in immature mouse testes, and studies were designed to investigate its pathway of synthesis, the steroid 5α-reductase isoenzyme involved in its formation, and whether testicular androstanediol is formed in embryonic mouse testes at the time of male phenotypic development. In 24-26-day-old immature testes, androstanediol is formed by two pathways; the predominant one involves testosterone → dihydrotestosterone → androstanediol, and a second utilizes the pathway progesterone → 5α-dihydroprogesterone → 5α-pregnane-3α-ol-20-one → 5α-pregnane-3α,17α-diol-20-one → androsterone → androstanediol. Formation of androstanediol was normal in testes from mice deficient in steroid 5α-reductase 2 but absent in testes from mice deficient in steroid 5α-reductase 1, indicating that isoenzyme 2 is not expressed in day 24-26 testes. The fact that androstenedione and testosterone were the only androgens identified after incubation of day 16 and 17 embryonic testes with [3H]progesterone implies that androstanediol formation in the testis plays no role in male phenotypic differentiation in the mouse.
KW - 17β-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5α-androstan-3-one
KW - 4MA
KW - 5α-androstane-3α,17β-diol
KW - Androstanediol
KW - HPLC
KW - Mouse testes
KW - Neonatal androgen
KW - Steroid 5α-reductase
KW - high-performance liquid chromatography
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U2 - 10.1016/j.mce.2004.04.009
DO - 10.1016/j.mce.2004.04.009
M3 - Article
C2 - 15249131
AN - SCOPUS:3142530379
SN - 0303-7207
VL - 222
SP - 113
EP - 120
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -