Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Delta(7)-sterol reductase (Dhcr7), the enzyme associated with Smith-Lemli-Opitz syndrome

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Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Delta(7)-sterol reductase (Dhcr7), the enzyme associated with Smith-Lemli-Opitz syndrome. / Matabosch, X; Rahman, M; Hughes, Beverly; Patel, SB; Watson, G; Shackleton, C.

In: The Journal of Steroid Biochemistry and Molecular Biology, Vol. 116, No. 1-2, 01.08.2009, p. 61-70.

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@article{d07615dd84564c98aa3d374942478f36,
title = "Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Delta(7)-sterol reductase (Dhcr7), the enzyme associated with Smith-Lemli-Opitz syndrome",
abstract = "This study has shown that the mouse has a great increase in steroid production during pregnancy in similar fashion to the human. Many steroids were provisionally identified in maternal urine of the wild-type mouse. The major progesterone metabolites appear to be hydroxylated pregnanolones, particularly with hydroxyl groups in the 16 alpha position. Rather than estriol being the major end-product of feto-placental steroid synthesis as in the human, the pregnant mouse produces and excretes large amounts of androgen metabolites, ranging in polarity from androstanetriols to androstanepentols. These steroids have 15 alpha or 18-hydroxyl groups with additional hydroxylation at uncharacterized positions. From metabolite data the peak of pregnancy progesterone production appears to be between 7.5 and 14.5 gestational days, while for C-19 metabolites peak excretion is later. The starting-point of the studies was to study pregnancy steroid production by a mouse model for Smith-Lemli-Opitz syndrome, 7-dehydrosterol reductase (DHCR7) deficiency. In human pregnancies with DHCR7 deficient fetuses large amounts of 7- and 8-dehydrosteroids are excreted, products secondary to high fetal 7- and 8-dehydrocholesterol (DHC) accumulation. This agrees with existing evidence that human feto-placental steroid synthesis utilizes little maternal cholesterol as precursor. In contrast, this study has shown that pregnant mice carrying dhcr7 deficient fetuses with relatively high DHC production had essentially undetectable maternal excretions of steroids with Delta(7)- and Delta(8)-unsaturation. As mutant mouse mothers have essentially normal cholesterol production (little or no DHC build-up), this suggests maternal cholesterol is primarily utilized for pregnancy steroid synthesis in the mouse. Published by Elsevier Ltd.",
keywords = "Smith-Lemli-Opitz syndrome, DHCR7, Mouse pregnancy steroids, GC/MS, SLOS",
author = "X Matabosch and M Rahman and Beverly Hughes and SB Patel and G Watson and C Shackleton",
year = "2009",
month = aug,
day = "1",
doi = "10.1016/j.jsbmb.2009.04.011",
language = "English",
volume = "116",
pages = "61--70",
journal = "The Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier",
number = "1-2",

}

RIS

TY - JOUR

T1 - Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Delta(7)-sterol reductase (Dhcr7), the enzyme associated with Smith-Lemli-Opitz syndrome

AU - Matabosch, X

AU - Rahman, M

AU - Hughes, Beverly

AU - Patel, SB

AU - Watson, G

AU - Shackleton, C

PY - 2009/8/1

Y1 - 2009/8/1

N2 - This study has shown that the mouse has a great increase in steroid production during pregnancy in similar fashion to the human. Many steroids were provisionally identified in maternal urine of the wild-type mouse. The major progesterone metabolites appear to be hydroxylated pregnanolones, particularly with hydroxyl groups in the 16 alpha position. Rather than estriol being the major end-product of feto-placental steroid synthesis as in the human, the pregnant mouse produces and excretes large amounts of androgen metabolites, ranging in polarity from androstanetriols to androstanepentols. These steroids have 15 alpha or 18-hydroxyl groups with additional hydroxylation at uncharacterized positions. From metabolite data the peak of pregnancy progesterone production appears to be between 7.5 and 14.5 gestational days, while for C-19 metabolites peak excretion is later. The starting-point of the studies was to study pregnancy steroid production by a mouse model for Smith-Lemli-Opitz syndrome, 7-dehydrosterol reductase (DHCR7) deficiency. In human pregnancies with DHCR7 deficient fetuses large amounts of 7- and 8-dehydrosteroids are excreted, products secondary to high fetal 7- and 8-dehydrocholesterol (DHC) accumulation. This agrees with existing evidence that human feto-placental steroid synthesis utilizes little maternal cholesterol as precursor. In contrast, this study has shown that pregnant mice carrying dhcr7 deficient fetuses with relatively high DHC production had essentially undetectable maternal excretions of steroids with Delta(7)- and Delta(8)-unsaturation. As mutant mouse mothers have essentially normal cholesterol production (little or no DHC build-up), this suggests maternal cholesterol is primarily utilized for pregnancy steroid synthesis in the mouse. Published by Elsevier Ltd.

AB - This study has shown that the mouse has a great increase in steroid production during pregnancy in similar fashion to the human. Many steroids were provisionally identified in maternal urine of the wild-type mouse. The major progesterone metabolites appear to be hydroxylated pregnanolones, particularly with hydroxyl groups in the 16 alpha position. Rather than estriol being the major end-product of feto-placental steroid synthesis as in the human, the pregnant mouse produces and excretes large amounts of androgen metabolites, ranging in polarity from androstanetriols to androstanepentols. These steroids have 15 alpha or 18-hydroxyl groups with additional hydroxylation at uncharacterized positions. From metabolite data the peak of pregnancy progesterone production appears to be between 7.5 and 14.5 gestational days, while for C-19 metabolites peak excretion is later. The starting-point of the studies was to study pregnancy steroid production by a mouse model for Smith-Lemli-Opitz syndrome, 7-dehydrosterol reductase (DHCR7) deficiency. In human pregnancies with DHCR7 deficient fetuses large amounts of 7- and 8-dehydrosteroids are excreted, products secondary to high fetal 7- and 8-dehydrocholesterol (DHC) accumulation. This agrees with existing evidence that human feto-placental steroid synthesis utilizes little maternal cholesterol as precursor. In contrast, this study has shown that pregnant mice carrying dhcr7 deficient fetuses with relatively high DHC production had essentially undetectable maternal excretions of steroids with Delta(7)- and Delta(8)-unsaturation. As mutant mouse mothers have essentially normal cholesterol production (little or no DHC build-up), this suggests maternal cholesterol is primarily utilized for pregnancy steroid synthesis in the mouse. Published by Elsevier Ltd.

KW - Smith-Lemli-Opitz syndrome

KW - DHCR7

KW - Mouse pregnancy steroids

KW - GC/MS

KW - SLOS

U2 - 10.1016/j.jsbmb.2009.04.011

DO - 10.1016/j.jsbmb.2009.04.011

M3 - Article

C2 - 19406241

VL - 116

SP - 61

EP - 70

JO - The Journal of Steroid Biochemistry and Molecular Biology

JF - The Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 1-2

ER -