Characterization of Human Adrenal Steroidogenesis During Fetal Development

Cecilie Melau; John Erik Nielsen; Hanne Frederiksen; Karen Kilcoyne; Signe Perlman; Lene Lundvall; Lea Langhoff Thuesen; Kristine Juul Hare; Anna-Maria Andersson; Rod T Mitchell; Anders Juul; Anne Jørgensen

doi:10.1210/jc.2018-01759

Characterization of Human Adrenal Steroidogenesis During Fetal Development

Cecilie Melau, John Erik Nielsen, Hanne Frederiksen, Karen Kilcoyne, Signe Perlman, Lene Lundvall, Lea Langhoff Thuesen, Kristine Juul Hare, Anna-Maria Andersson, Rod T Mitchell, Anders Juul, Anne Jørgensen

Department of Clinical Medicine

7 Citations (Scopus)

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Abstract

Context: The endocrine function of human fetal adrenals (HFAs) is activated already during first trimester, but adrenal steroidogenesis during fetal life is not well characterized. Objective: This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from first and second trimesters. Design and Setting: Male and female HFA from gestational weeks (GWs) 8 to 19 were examined, including a total of 101 samples from 83 fetuses. Main Outcome Measure(s): Expression level of steroidogenic genes and protein expression/localization were determined by quantitative PCR and immunohistochemistry, respectively, and intra-adrenal steroid levels were quantified by LC-MS/MS. Results: Transcriptional levels of StAR, CYP11A1, CYP17A1, CYP21A2, CYP11B1/2, and SULT2A1 were significantly higher in second trimester compared to first trimester (P < 0.05), whereas expression levels of 3β-HSD2 and ARK1C3 were unaltered between GWs 8 and 19. All investigated steroidogenic proteins were expressed in a distinct pattern throughout the investigated period, with most enzymes expressed primarily in the fetal zone, except 3β-HSD1/2, which was expressed mainly in the definitive zone. Abundant steroidogenic enzyme expression was reflected in overall high intra-adrenal tissue concentrations of mineralocorticoids, glucocorticoids, and androgens; cortisol was the most abundant (1071 to 2723 ng/g tissue), and testosterone levels were the lowest (2 to 14 ng/g tissue). Conclusions: The expression profiles of HFA steroidogenic enzymes are distinct from first to second trimester, with no major differences between male and female samples. Intra-adrenal steroid hormone concentrations confirm that cortisol is produced throughout first and second trimesters, suggesting continued regulation of the hypothalamus-pituitary-adrenal axis during this entire period.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	104
Issue number	5
Pages (from-to)	1802-1812
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2018-01759
Publication status	Published - 2019

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Melau, C., Nielsen, J. E., Frederiksen, H., Kilcoyne, K., Perlman, S., Lundvall, L., Langhoff Thuesen, L., Juul Hare, K., Andersson, A.-M., Mitchell, R. T., Juul, A., & Jørgensen, A. (2019). Characterization of Human Adrenal Steroidogenesis During Fetal Development. The Journal of clinical endocrinology and metabolism, 104(5), 1802-1812. https://doi.org/10.1210/jc.2018-01759

Melau, C, Nielsen, JE, Frederiksen, H, Kilcoyne, K, Perlman, S, Lundvall, L, Langhoff Thuesen, L, Juul Hare, K, Andersson, A-M, Mitchell, RT, Juul, A & Jørgensen, A 2019, 'Characterization of Human Adrenal Steroidogenesis During Fetal Development', The Journal of clinical endocrinology and metabolism, vol. 104, no. 5, pp. 1802-1812. https://doi.org/10.1210/jc.2018-01759

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title = "Characterization of Human Adrenal Steroidogenesis During Fetal Development",

abstract = "Context: The endocrine function of human fetal adrenals (HFAs) is activated already during first trimester, but adrenal steroidogenesis during fetal life is not well characterized. Objective: This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from first and second trimesters. Design and Setting: Male and female HFA from gestational weeks (GWs) 8 to 19 were examined, including a total of 101 samples from 83 fetuses. Main Outcome Measure(s): Expression level of steroidogenic genes and protein expression/localization were determined by quantitative PCR and immunohistochemistry, respectively, and intra-adrenal steroid levels were quantified by LC-MS/MS. Results: Transcriptional levels of StAR, CYP11A1, CYP17A1, CYP21A2, CYP11B1/2, and SULT2A1 were significantly higher in second trimester compared to first trimester (P < 0.05), whereas expression levels of 3β-HSD2 and ARK1C3 were unaltered between GWs 8 and 19. All investigated steroidogenic proteins were expressed in a distinct pattern throughout the investigated period, with most enzymes expressed primarily in the fetal zone, except 3β-HSD1/2, which was expressed mainly in the definitive zone. Abundant steroidogenic enzyme expression was reflected in overall high intra-adrenal tissue concentrations of mineralocorticoids, glucocorticoids, and androgens; cortisol was the most abundant (1071 to 2723 ng/g tissue), and testosterone levels were the lowest (2 to 14 ng/g tissue). Conclusions: The expression profiles of HFA steroidogenic enzymes are distinct from first to second trimester, with no major differences between male and female samples. Intra-adrenal steroid hormone concentrations confirm that cortisol is produced throughout first and second trimesters, suggesting continued regulation of the hypothalamus-pituitary-adrenal axis during this entire period.",

author = "Cecilie Melau and Nielsen, {John Erik} and Hanne Frederiksen and Karen Kilcoyne and Signe Perlman and Lene Lundvall and {Langhoff Thuesen}, Lea and {Juul Hare}, Kristine and Anna-Maria Andersson and Mitchell, {Rod T} and Anders Juul and Anne J{\o}rgensen",

note = "Copyright {\textcopyright} 2019 Endocrine Society.",

year = "2019",

doi = "10.1210/jc.2018-01759",

language = "English",

volume = "104",

pages = "1802--1812",

journal = "The Journal of clinical endocrinology and metabolism",

issn = "0021-972X",

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TY - JOUR

T1 - Characterization of Human Adrenal Steroidogenesis During Fetal Development

AU - Melau, Cecilie

AU - Nielsen, John Erik

AU - Frederiksen, Hanne

AU - Kilcoyne, Karen

AU - Perlman, Signe

AU - Lundvall, Lene

AU - Langhoff Thuesen, Lea

AU - Juul Hare, Kristine

AU - Andersson, Anna-Maria

AU - Mitchell, Rod T

AU - Juul, Anders

AU - Jørgensen, Anne

PY - 2019

Y1 - 2019

N2 - Context: The endocrine function of human fetal adrenals (HFAs) is activated already during first trimester, but adrenal steroidogenesis during fetal life is not well characterized. Objective: This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from first and second trimesters. Design and Setting: Male and female HFA from gestational weeks (GWs) 8 to 19 were examined, including a total of 101 samples from 83 fetuses. Main Outcome Measure(s): Expression level of steroidogenic genes and protein expression/localization were determined by quantitative PCR and immunohistochemistry, respectively, and intra-adrenal steroid levels were quantified by LC-MS/MS. Results: Transcriptional levels of StAR, CYP11A1, CYP17A1, CYP21A2, CYP11B1/2, and SULT2A1 were significantly higher in second trimester compared to first trimester (P < 0.05), whereas expression levels of 3β-HSD2 and ARK1C3 were unaltered between GWs 8 and 19. All investigated steroidogenic proteins were expressed in a distinct pattern throughout the investigated period, with most enzymes expressed primarily in the fetal zone, except 3β-HSD1/2, which was expressed mainly in the definitive zone. Abundant steroidogenic enzyme expression was reflected in overall high intra-adrenal tissue concentrations of mineralocorticoids, glucocorticoids, and androgens; cortisol was the most abundant (1071 to 2723 ng/g tissue), and testosterone levels were the lowest (2 to 14 ng/g tissue). Conclusions: The expression profiles of HFA steroidogenic enzymes are distinct from first to second trimester, with no major differences between male and female samples. Intra-adrenal steroid hormone concentrations confirm that cortisol is produced throughout first and second trimesters, suggesting continued regulation of the hypothalamus-pituitary-adrenal axis during this entire period.

AB - Context: The endocrine function of human fetal adrenals (HFAs) is activated already during first trimester, but adrenal steroidogenesis during fetal life is not well characterized. Objective: This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from first and second trimesters. Design and Setting: Male and female HFA from gestational weeks (GWs) 8 to 19 were examined, including a total of 101 samples from 83 fetuses. Main Outcome Measure(s): Expression level of steroidogenic genes and protein expression/localization were determined by quantitative PCR and immunohistochemistry, respectively, and intra-adrenal steroid levels were quantified by LC-MS/MS. Results: Transcriptional levels of StAR, CYP11A1, CYP17A1, CYP21A2, CYP11B1/2, and SULT2A1 were significantly higher in second trimester compared to first trimester (P < 0.05), whereas expression levels of 3β-HSD2 and ARK1C3 were unaltered between GWs 8 and 19. All investigated steroidogenic proteins were expressed in a distinct pattern throughout the investigated period, with most enzymes expressed primarily in the fetal zone, except 3β-HSD1/2, which was expressed mainly in the definitive zone. Abundant steroidogenic enzyme expression was reflected in overall high intra-adrenal tissue concentrations of mineralocorticoids, glucocorticoids, and androgens; cortisol was the most abundant (1071 to 2723 ng/g tissue), and testosterone levels were the lowest (2 to 14 ng/g tissue). Conclusions: The expression profiles of HFA steroidogenic enzymes are distinct from first to second trimester, with no major differences between male and female samples. Intra-adrenal steroid hormone concentrations confirm that cortisol is produced throughout first and second trimesters, suggesting continued regulation of the hypothalamus-pituitary-adrenal axis during this entire period.

U2 - 10.1210/jc.2018-01759

DO - 10.1210/jc.2018-01759

M3 - Journal article

C2 - 30590593

SN - 0021-972X

VL - 104

SP - 1802

EP - 1812

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 5

ER -

Characterization of Human Adrenal Steroidogenesis During Fetal Development

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