Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Jun;53(6):1709–1715. doi: 10.1172/JCI107722

Effect of Maternal Intrahepatic Cholestasis on Fetal Steroid Metabolism

Timo J Laatikainen 1,2, Jari I Peltonen 1,2, Pekka L Nylander 1,2
PMCID: PMC302667  PMID: 4275337

Abstract

Estriol, estriol sulfate, progesterone, and 17 neutral steroid sulfates, including estriol precursors and progesterone metabolites, were determined in 27 cord plasma samples collected after pregnancies complicated by intrahepatic cholestasis of the mother. The levels of these steroids were compared with those in the cord plasma of 42 healthy controls.

In the cord plasma, the steroid profile after pregnancies complicated by maternal intrahepatic cholestasis differed greatly from that seen after uncomplicated pregnancy. Two main differences were found. In the disulfate fraction, the concentrations of two pregnanediol isomers, 5α-pregnane-3α,20α-diol and 5β-pregnane-3α,20α-diol, were high after cholestasis. Other investigators have shown that, as a result of cholestasis, these pregnanediol sulfates circulate in greatly elevated amounts in the maternal plasma. Our results indicate that in cholestasis these steroids cross the placenta into the fetal compartment, where they circulate in elevated amounts as disulfates. Secondly, the concentrations of several steroid sulfates known to be synthesized by the fetus were significantly lower in the cholestasis group than in the healthy controls. This was especially true of 16α-hydroxydehydroepiandrosterone sulfate and 16α-hydroxypregnenolone sulfate. These results suggest that, in pregnancies complicated by maternal intrahepatic cholestasis, impairment of fetal steroid synthesis, and especially of 16α-hydroxylation, occurs in the fetal compartment.

Thus, the changes in maternal steroid metabolism caused by cholestasis are reflected in the steroid profile of the fetoplacental circulation. Furthermore, maternal intrahepatic cholestasis may result in the production of some substance which crosses the placenta and affects fetal steroid metabolism.

Full text

PDF
1709

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARIAS I. M., GARTNER L. M., SEIFTER S., FURMAN M. PROLONGED NEONATAL UNCONJUGATED HYPERBILIRUBINEMIA ASSOCIATED WITH BREAST FEEDING AND A STEROID, PREGNANE-3(ALPHA), 20(BETA)-DIOL, IN MATERNAL MILK THAT INHIBITS GLUCURONIDE FORMATION IN VITRO. J Clin Invest. 1964 Nov;43:2037–2047. doi: 10.1172/JCI105078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adlercreutz H., Tenhunen R. Some aspects of the interaction between natural and synthetic female sex hormones and the liver. Am J Med. 1970 Nov;49:630–648. doi: 10.1016/s0002-9343(70)80130-9. [DOI] [PubMed] [Google Scholar]
  3. Archer D. F., Mathur R. S., Wiqvist N., Diczfalusy E. Quantitative assessment of the de novo sterol and steroid synthesis in the human foeto-placental unit. 2. Synthesis and secretion of steroids and steroid sulphates by the midgestation foetus. Acta Endocrinol (Copenh) 1971 Apr;66(4):666–678. doi: 10.1530/acta.0.0660666. [DOI] [PubMed] [Google Scholar]
  4. Friedlaender P., Osler M. Icterus and pregnancy. Am J Obstet Gynecol. 1967 Apr 1;97(7):894–900. doi: 10.1016/0002-9378(67)90513-3. [DOI] [PubMed] [Google Scholar]
  5. HSIA D. Y., DOWBEN R. M., RIABOV S. INHIBITORS OF GLUCURONYL TRANSFERASE IN THE NEWBORN. Ann N Y Acad Sci. 1963 Dec 30;111:326–336. doi: 10.1111/j.1749-6632.1963.tb36975.x. [DOI] [PubMed] [Google Scholar]
  6. Hellman L., Zumoff B., Fishman J., Gallagher T. F. Estradiol metabolism in total extrahepatic biliary obstruction. J Clin Endocrinol Metab. 1970 Feb;30(2):161–165. doi: 10.1210/jcem-30-2-161. [DOI] [PubMed] [Google Scholar]
  7. Huhtaniemi I., Luukkainen T., Vihko R. Identification and determination of neutral steroid sulphates in human foetal adrenal and liver tissue. Acta Endocrinol (Copenh) 1970 Jun;64(2):273–286. doi: 10.1530/acta.0.0640273. [DOI] [PubMed] [Google Scholar]
  8. Huhtaniemi I., Vihko R. Determination of unconjugated and sulfated neutral steroids in human fetal blood of early and mid-pregnancy. Steroids. 1970 Aug;16(2):197–206. doi: 10.1016/s0039-128x(70)80105-2. [DOI] [PubMed] [Google Scholar]
  9. Laatikainen T., Karjalainen O. Excertion of progesterone metabolites in urine and bile of pregnant women with intrahepatic cholestasis. J Steroid Biochem. 1973 Nov;4(6):641–648. doi: 10.1016/0022-4731(73)90039-3. [DOI] [PubMed] [Google Scholar]
  10. Laatikainen T., Karjalainen O. Excretion of conjugates of neutral steroids in human bile during late pregnancy. Acta Endocrinol (Copenh) 1972 Apr;69(4):775–788. doi: 10.1530/acta.0.0690775. [DOI] [PubMed] [Google Scholar]
  11. Laatikainen T., Peltonen J., Nylander P. Determination of estriol, estriol sulfate, progesterone and neutral steroid mono- and disulfates in umbilical cord blood plasma. Steroids. 1973 Mar;21(3):347–359. doi: 10.1016/0039-128x(73)90029-9. [DOI] [PubMed] [Google Scholar]
  12. PULKKINEN M. O. Arylsulphatase and the hydrolysis of some steroid sulphates in developing organism and placenta. Acta Physiol Scand Suppl. 1961;52(180):1–92. [PubMed] [Google Scholar]
  13. Sjövall J., Sjövall K. Steroid sulphates in plasma from pregnant women with pruritus and elevated plasma bile acid levels. Ann Clin Res. 1970 Dec;2(4):321–337. [PubMed] [Google Scholar]
  14. Sjövall K., Sjövall J. Serum bile acid levels in pregnancy with pruritus (bile acids and steroids 158). Clin Chim Acta. 1966 Feb;13(2):207–211. doi: 10.1016/0009-8981(66)90294-4. [DOI] [PubMed] [Google Scholar]
  15. Song C. S., Rifkind A. B., Gillette P. N., Kappas A. Hormones and the liver. The effect of estrogens, progestins, and pregnancy on hepatic function. Am J Obstet Gynecol. 1969 Nov 1;105(5):813–847. [PubMed] [Google Scholar]
  16. Telegdy G., Weeks J. W., Archer D. F., Wiqvist N., Diczfalusy E. Acetate and cholesterol metabolism in the human foeto-placental unit at midgestation. 2. Steroids synthesized and secreted by the foetus. Acta Endocrinol (Copenh) 1970 Jan;63(1):119–133. doi: 10.1530/acta.0.0630119. [DOI] [PubMed] [Google Scholar]
  17. WENGLE B. STUDIES ON ESTER SULPHATES. 21. ON SULPHATE CONJUGATION IN FOETAL HUMAN TISSUE EXTRACTS. Acta Soc Med Ups. 1964;69:105–124. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES