Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Δ7-sterol reductase (Dhcr7), the enzyme associated with Smith-Lemli-Opitz syndrome

Xavier Matabosch, Mahbuba Rahman, Beverly Hughes, Shailendra B. Patel, Gordon Watson, Cedric Shackleton

Research output: Contribution to journalArticle

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 16α 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 15α- 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 C19 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 Δ7- and Δ8-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.

Original languageEnglish
Pages (from-to)61-70
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume116
Issue number1-2
DOIs
Publication statusPublished - Aug 2009
Externally publishedYes

Fingerprint

Smith-Lemli-Opitz Syndrome
Sterols
Oxidoreductases
Fetus
Steroids
Pregnancy
Enzymes
Metabolites
Dehydrocholesterols
Mothers
Cholesterol
Hydroxyl Radical
Progesterone
Pregnanolone
Hydroxylation
Estriol
Androgens
Urine

Keywords

  • DHCR7
  • GC/MS
  • Mouse pregnancy steroids
  • SLOS
  • Smith-Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Molecular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Cell Biology
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Steroid production and excretion by the pregnant mouse, particularly in relation to pregnancies with fetuses deficient in Δ7-sterol reductase (Dhcr7), the enzyme associated with Smith-Lemli-Opitz syndrome. / Matabosch, Xavier; Rahman, Mahbuba; Hughes, Beverly; Patel, Shailendra B.; Watson, Gordon; Shackleton, Cedric.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 116, No. 1-2, 08.2009, p. 61-70.

Research output: Contribution to journalArticle

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