TY - JOUR
T1 - Isolation of a new mouse 3β-hydroxysteroid dehydrogenase isoform, 3β- HSD VI, expressed during early pregnancy
AU - Abbaszade, Ilgar G.
AU - Arensburg, Jonathan
AU - Park, Chang Hyun J.
AU - Kasa-Vubu, Josephine Z.
AU - Orly, Joseph
AU - Payne, Anita H.
PY - 1997
Y1 - 1997
N2 - The enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) is a key enzyme in the biosynthesis of steroid hormones. To date, this laboratory has isolated and characterized five distinct 3β-HSD complementary DNAs (cDNAs) in the mouse (3β-HSD I through V). These different forms are expressed in a tissue- and developmentally-specific manner and fall into two functionally distinct enzymes. 3β-HSD I and III, and most likely II, function as dehydrogenase/isomerases, whereas 3β-HSD IV and V function as 3-ketosteroid reductases. This study describes the isolation, characterization, and tissue- specific expression of a sixth member of this gene family, 3β-HSD VI. This new isoform functions as an NAD+-dependent dehydrogenase/isomerase exhibiting very low Michaelis-Menten constant (K(m)) values for pregnenolone (~0.035 μM) and dehydroepiandrosterone (~0.12 μM). 3β-HSD VI is the earliest isoform to be expressed during embryogenesis in cells of embryonic origin at 7 and 9.5 days postcoitum (pc), and is the major isoform expressed in uterine tissue at the time of implantation (4.5 days pc) and continues to be expressed in uterine tissue at 6.5, 7.5, and 9.5 days pc. 3β-HSD VI is expressed in giant trophoblasts at 9.5 days pc and is expressed in the placenta through day 15.5 pc. In the adult mouse, 3β-HSD VI appears to be the only isoform expressed in the skin and also is expressed in the testis, but to a lesser extent than 3β-HSD I. Mouse 3β-HSD VI cDNA is orthologous to human 3β-HSD I cDNA. Human type I 3β-HSD has been shown to be the only isoform expressed in the placenta and skin. The demonstration that mouse 3β- HSD VI functions as a dehydrogenase/isomerase and is the predominant isoform expressed during the first half of pregnancy in uterine tissue and in embryonic cells suggests that this isoform may be involved in local production of progesterone, which is needed for successful implantation of the blastocyst and/or maintenance of early pregnancy.
AB - The enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD) is a key enzyme in the biosynthesis of steroid hormones. To date, this laboratory has isolated and characterized five distinct 3β-HSD complementary DNAs (cDNAs) in the mouse (3β-HSD I through V). These different forms are expressed in a tissue- and developmentally-specific manner and fall into two functionally distinct enzymes. 3β-HSD I and III, and most likely II, function as dehydrogenase/isomerases, whereas 3β-HSD IV and V function as 3-ketosteroid reductases. This study describes the isolation, characterization, and tissue- specific expression of a sixth member of this gene family, 3β-HSD VI. This new isoform functions as an NAD+-dependent dehydrogenase/isomerase exhibiting very low Michaelis-Menten constant (K(m)) values for pregnenolone (~0.035 μM) and dehydroepiandrosterone (~0.12 μM). 3β-HSD VI is the earliest isoform to be expressed during embryogenesis in cells of embryonic origin at 7 and 9.5 days postcoitum (pc), and is the major isoform expressed in uterine tissue at the time of implantation (4.5 days pc) and continues to be expressed in uterine tissue at 6.5, 7.5, and 9.5 days pc. 3β-HSD VI is expressed in giant trophoblasts at 9.5 days pc and is expressed in the placenta through day 15.5 pc. In the adult mouse, 3β-HSD VI appears to be the only isoform expressed in the skin and also is expressed in the testis, but to a lesser extent than 3β-HSD I. Mouse 3β-HSD VI cDNA is orthologous to human 3β-HSD I cDNA. Human type I 3β-HSD has been shown to be the only isoform expressed in the placenta and skin. The demonstration that mouse 3β- HSD VI functions as a dehydrogenase/isomerase and is the predominant isoform expressed during the first half of pregnancy in uterine tissue and in embryonic cells suggests that this isoform may be involved in local production of progesterone, which is needed for successful implantation of the blastocyst and/or maintenance of early pregnancy.
UR - http://www.scopus.com/inward/record.url?scp=0031004827&partnerID=8YFLogxK
U2 - 10.1210/endo.138.4.5042
DO - 10.1210/endo.138.4.5042
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C2 - 9075693
AN - SCOPUS:0031004827
SN - 0013-7227
VL - 138
SP - 1392
EP - 1399
JO - Endocrinology
JF - Endocrinology
IS - 4
ER -