Steroidogenic enzyme expression in the human fetal liver and potential role in the endocrinology of pregnancy

P. J. O'Shaughnessy, A. Monteiro, S. Bhattacharya, M. J. Fraser, P. A. Fowler

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The human feto-maternal unit produces large amounts of steroid hormones, particularly estrogens, during the second and third trimesters. The fetal adrenal gland and the placenta are considered the principal tissues driving steroid production but the fetal liver is likely to play an essential role in this process. This study was designed to measure transcript expression of proteins involved in steroid synthesis, metabolism, conjugation and signaling in the human fetal liver and to examine sex differences and effects of maternal smoking. Liver samples were taken from 55 normal fetuses from women undergoing second trimester elective termination. Levels of 23 mRNA transcripts encoding steroid synthesis/ metabolic/conjugation enzymes and steroid receptors were measured by real-time PCR. Expression of representative proteins was confirmed by Western blotting and immunohistochemistry. The human fetal livers expressed high levels of CYP19A1, SULT 2A1, SULT1E1, HSD17B2, SRD5A3 and CYP3A7. Lower levels of SULT1A1, STS, UGT2B17, GPER, AKR1C3, UGT2B15, AR, CYP11A1, CYP21A2, HSD17B3, HSD17B1 and SRD5A1 were also detectable. Expression of ESR, ESR2, CYP17A1 and HSD3B transcripts was undetectable in most fetal livers although HSD3B was shown to be present by Western blotting. Sex differences were limited to SRD5A3 (lower in females) and UGT2B17 (higher in females). Maternal smoking increased expression of CYP19A1, SULT2A1, UGT2B17, HSD17B2 and AKR1C3 and reduced expression of SRD5A3 in the male fetal liver. This study shows that the human fetal liver is likely to have an extensive effect on circulating steroid levels in the human fetus and mother. The most important of these effects will be alterations to the species, conjugation and availability of estrogens in the fetus. Maternal smoking is likely to reduce circulating androgen bioactivity in male fetuses.
Original languageEnglish
Pages (from-to)177-187
Number of pages11
JournalMolecular Human Reproduction
Volume19
Issue number3
Early online date29 Nov 2012
DOIs
Publication statusPublished - Mar 2013

Fingerprint

Endocrinology
Pregnancy
Liver
Steroids
Enzymes
Mothers
Fetus
Smoking
Second Pregnancy Trimester
Sex Characteristics
Estrogens
Western Blotting
Cholesterol Side-Chain Cleavage Enzyme
Steroid Receptors
Third Pregnancy Trimester
Adrenal Glands
Placenta
Androgens
Real-Time Polymerase Chain Reaction
Proteins

Keywords

  • steroidogenesis
  • conjugation
  • estrogen
  • androgen
  • placenta

Cite this

Steroidogenic enzyme expression in the human fetal liver and potential role in the endocrinology of pregnancy. / O'Shaughnessy, P. J.; Monteiro, A.; Bhattacharya, S.; Fraser, M. J.; Fowler, P. A.

In: Molecular Human Reproduction, Vol. 19, No. 3, 03.2013, p. 177-187.

Research output: Contribution to journalArticle

@article{4f00104c9e944004ad84acb7b94c9174,
title = "Steroidogenic enzyme expression in the human fetal liver and potential role in the endocrinology of pregnancy",
abstract = "The human feto-maternal unit produces large amounts of steroid hormones, particularly estrogens, during the second and third trimesters. The fetal adrenal gland and the placenta are considered the principal tissues driving steroid production but the fetal liver is likely to play an essential role in this process. This study was designed to measure transcript expression of proteins involved in steroid synthesis, metabolism, conjugation and signaling in the human fetal liver and to examine sex differences and effects of maternal smoking. Liver samples were taken from 55 normal fetuses from women undergoing second trimester elective termination. Levels of 23 mRNA transcripts encoding steroid synthesis/ metabolic/conjugation enzymes and steroid receptors were measured by real-time PCR. Expression of representative proteins was confirmed by Western blotting and immunohistochemistry. The human fetal livers expressed high levels of CYP19A1, SULT 2A1, SULT1E1, HSD17B2, SRD5A3 and CYP3A7. Lower levels of SULT1A1, STS, UGT2B17, GPER, AKR1C3, UGT2B15, AR, CYP11A1, CYP21A2, HSD17B3, HSD17B1 and SRD5A1 were also detectable. Expression of ESR, ESR2, CYP17A1 and HSD3B transcripts was undetectable in most fetal livers although HSD3B was shown to be present by Western blotting. Sex differences were limited to SRD5A3 (lower in females) and UGT2B17 (higher in females). Maternal smoking increased expression of CYP19A1, SULT2A1, UGT2B17, HSD17B2 and AKR1C3 and reduced expression of SRD5A3 in the male fetal liver. This study shows that the human fetal liver is likely to have an extensive effect on circulating steroid levels in the human fetus and mother. The most important of these effects will be alterations to the species, conjugation and availability of estrogens in the fetus. Maternal smoking is likely to reduce circulating androgen bioactivity in male fetuses.",
keywords = "steroidogenesis, conjugation, estrogen, androgen, placenta",
author = "O'Shaughnessy, {P. J.} and A. Monteiro and S. Bhattacharya and Fraser, {M. J.} and Fowler, {P. A.}",
year = "2013",
month = "3",
doi = "10.1093/molehr/gas059",
language = "English",
volume = "19",
pages = "177--187",
journal = "Molecular Human Reproduction",
issn = "1360-9947",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Steroidogenic enzyme expression in the human fetal liver and potential role in the endocrinology of pregnancy

AU - O'Shaughnessy, P. J.

AU - Monteiro, A.

AU - Bhattacharya, S.

AU - Fraser, M. J.

AU - Fowler, P. A.

PY - 2013/3

Y1 - 2013/3

N2 - The human feto-maternal unit produces large amounts of steroid hormones, particularly estrogens, during the second and third trimesters. The fetal adrenal gland and the placenta are considered the principal tissues driving steroid production but the fetal liver is likely to play an essential role in this process. This study was designed to measure transcript expression of proteins involved in steroid synthesis, metabolism, conjugation and signaling in the human fetal liver and to examine sex differences and effects of maternal smoking. Liver samples were taken from 55 normal fetuses from women undergoing second trimester elective termination. Levels of 23 mRNA transcripts encoding steroid synthesis/ metabolic/conjugation enzymes and steroid receptors were measured by real-time PCR. Expression of representative proteins was confirmed by Western blotting and immunohistochemistry. The human fetal livers expressed high levels of CYP19A1, SULT 2A1, SULT1E1, HSD17B2, SRD5A3 and CYP3A7. Lower levels of SULT1A1, STS, UGT2B17, GPER, AKR1C3, UGT2B15, AR, CYP11A1, CYP21A2, HSD17B3, HSD17B1 and SRD5A1 were also detectable. Expression of ESR, ESR2, CYP17A1 and HSD3B transcripts was undetectable in most fetal livers although HSD3B was shown to be present by Western blotting. Sex differences were limited to SRD5A3 (lower in females) and UGT2B17 (higher in females). Maternal smoking increased expression of CYP19A1, SULT2A1, UGT2B17, HSD17B2 and AKR1C3 and reduced expression of SRD5A3 in the male fetal liver. This study shows that the human fetal liver is likely to have an extensive effect on circulating steroid levels in the human fetus and mother. The most important of these effects will be alterations to the species, conjugation and availability of estrogens in the fetus. Maternal smoking is likely to reduce circulating androgen bioactivity in male fetuses.

AB - The human feto-maternal unit produces large amounts of steroid hormones, particularly estrogens, during the second and third trimesters. The fetal adrenal gland and the placenta are considered the principal tissues driving steroid production but the fetal liver is likely to play an essential role in this process. This study was designed to measure transcript expression of proteins involved in steroid synthesis, metabolism, conjugation and signaling in the human fetal liver and to examine sex differences and effects of maternal smoking. Liver samples were taken from 55 normal fetuses from women undergoing second trimester elective termination. Levels of 23 mRNA transcripts encoding steroid synthesis/ metabolic/conjugation enzymes and steroid receptors were measured by real-time PCR. Expression of representative proteins was confirmed by Western blotting and immunohistochemistry. The human fetal livers expressed high levels of CYP19A1, SULT 2A1, SULT1E1, HSD17B2, SRD5A3 and CYP3A7. Lower levels of SULT1A1, STS, UGT2B17, GPER, AKR1C3, UGT2B15, AR, CYP11A1, CYP21A2, HSD17B3, HSD17B1 and SRD5A1 were also detectable. Expression of ESR, ESR2, CYP17A1 and HSD3B transcripts was undetectable in most fetal livers although HSD3B was shown to be present by Western blotting. Sex differences were limited to SRD5A3 (lower in females) and UGT2B17 (higher in females). Maternal smoking increased expression of CYP19A1, SULT2A1, UGT2B17, HSD17B2 and AKR1C3 and reduced expression of SRD5A3 in the male fetal liver. This study shows that the human fetal liver is likely to have an extensive effect on circulating steroid levels in the human fetus and mother. The most important of these effects will be alterations to the species, conjugation and availability of estrogens in the fetus. Maternal smoking is likely to reduce circulating androgen bioactivity in male fetuses.

KW - steroidogenesis

KW - conjugation

KW - estrogen

KW - androgen

KW - placenta

U2 - 10.1093/molehr/gas059

DO - 10.1093/molehr/gas059

M3 - Article

C2 - 23197595

VL - 19

SP - 177

EP - 187

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

SN - 1360-9947

IS - 3

ER -