Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis. / Melau, Cecilie; Nielsen, John E.; Perlman, Signe; Lundvall, Lene; Langhoff Thuesen, Lea; Juul Hare, Kristine; Schou Hammerum, Mette; Frederiksen, Hanne; Mitchell, Rod T.; Juul, Anders; Jørgensen, Anne.

I: Journal of Clinical Endocrinology and Metabolism, Bind 106, Nr. 3, 01.03.2021, s. 843-857.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Melau, C, Nielsen, JE, Perlman, S, Lundvall, L, Langhoff Thuesen, L, Juul Hare, K, Schou Hammerum, M, Frederiksen, H, Mitchell, RT, Juul, A & Jørgensen, A 2021, 'Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis', Journal of Clinical Endocrinology and Metabolism, bind 106, nr. 3, s. 843-857. https://doi.org/10.1210/clinem/dgaa852

APA

Melau, C., Nielsen, J. E., Perlman, S., Lundvall, L., Langhoff Thuesen, L., Juul Hare, K., Schou Hammerum, M., Frederiksen, H., Mitchell, R. T., Juul, A., & Jørgensen, A. (2021). Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis. Journal of Clinical Endocrinology and Metabolism, 106(3), 843-857. https://doi.org/10.1210/clinem/dgaa852

Vancouver

Melau C, Nielsen JE, Perlman S, Lundvall L, Langhoff Thuesen L, Juul Hare K o.a. Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis. Journal of Clinical Endocrinology and Metabolism. 2021 mar. 1;106(3):843-857. https://doi.org/10.1210/clinem/dgaa852

Author

Melau, Cecilie ; Nielsen, John E. ; Perlman, Signe ; Lundvall, Lene ; Langhoff Thuesen, Lea ; Juul Hare, Kristine ; Schou Hammerum, Mette ; Frederiksen, Hanne ; Mitchell, Rod T. ; Juul, Anders ; Jørgensen, Anne. / Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis. I: Journal of Clinical Endocrinology and Metabolism. 2021 ; Bind 106, Nr. 3. s. 843-857.

Bibtex

@article{8658a4486b644c00a1276518152fb667,

title = "Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis",

abstract = "Context: Disorders affecting adrenal steroidogenesis promote an imbalance in the normally tightly controlled secretion of mineralocorticoids, glucocorticoids, and androgens. This may lead to differences/disorders of sex development in the fetus, as seen in virilized girls with congenital adrenal hyperplasia (CAH). Despite the important endocrine function of human fetal adrenals, neither normal nor dysregulated adrenal steroidogenesis is understood in detail. Objective: Due to significant differences in adrenal steroidogenesis between human and model species (except higher primates), we aimed to establish a human fetal adrenal model that enables examination of both de novo and manipulated adrenal steroidogenesis. Design and Setting: Human adrenal tissue from 54 1st trimester fetuses were cultured ex vivo as intact tissue fragments for 7 or 14 days. Main Outcome Measures: Model validation included examination of postculture tissue morphology, viability, apoptosis, and quantification of steroid hormones secreted to the culture media measured by liquid chromatography-tandem mass spectrometry. Results: The culture approach maintained cell viability, preserved cell populations of all fetal adrenal zones, and recapitulated de novo adrenal steroidogenesis based on continued secretion of steroidogenic intermediates, glucocorticoids, and androgens. Adrenocorticotropic hormone and ketoconazole treatment of ex vivo cultured human fetal adrenal tissue resulted in the stimulation of steroidogenesis and inhibition of androgen secretion, respectively, demonstrating a treatment-specific response. Conclusions: Together, these data indicate that ex vivo culture of human fetal adrenal tissue constitutes a novel approach to investigate local effects of pharmaceutical exposures or emerging therapeutic options targeting imbalanced steroidogenesis in adrenal disorders, including CAH. ",

keywords = "ACTH, androgen biosynthesis, endocrine activity, ex vivo culture, ketoconazole, steroidogenesis",

author = "Cecilie Melau and Nielsen, {John E.} and Signe Perlman and Lene Lundvall and {Langhoff Thuesen}, Lea and {Juul Hare}, Kristine and {Schou Hammerum}, Mette and Hanne Frederiksen and Mitchell, {Rod T.} and Anders Juul and Anne J{\o}rgensen",

year = "2021",

month = mar,

day = "1",

doi = "10.1210/clinem/dgaa852",

language = "English",

volume = "106",

pages = "843--857",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "3",

}

RIS

TY - JOUR

T1 - Establishment of a Novel Human Fetal Adrenal Culture Model that Supports de Novo and Manipulated Steroidogenesis

AU - Melau, Cecilie

AU - Nielsen, John E.

AU - Perlman, Signe

AU - Lundvall, Lene

AU - Langhoff Thuesen, Lea

AU - Juul Hare, Kristine

AU - Schou Hammerum, Mette

AU - Frederiksen, Hanne

AU - Mitchell, Rod T.

AU - Juul, Anders

AU - Jørgensen, Anne

PY - 2021/3/1

Y1 - 2021/3/1

N2 - Context: Disorders affecting adrenal steroidogenesis promote an imbalance in the normally tightly controlled secretion of mineralocorticoids, glucocorticoids, and androgens. This may lead to differences/disorders of sex development in the fetus, as seen in virilized girls with congenital adrenal hyperplasia (CAH). Despite the important endocrine function of human fetal adrenals, neither normal nor dysregulated adrenal steroidogenesis is understood in detail. Objective: Due to significant differences in adrenal steroidogenesis between human and model species (except higher primates), we aimed to establish a human fetal adrenal model that enables examination of both de novo and manipulated adrenal steroidogenesis. Design and Setting: Human adrenal tissue from 54 1st trimester fetuses were cultured ex vivo as intact tissue fragments for 7 or 14 days. Main Outcome Measures: Model validation included examination of postculture tissue morphology, viability, apoptosis, and quantification of steroid hormones secreted to the culture media measured by liquid chromatography-tandem mass spectrometry. Results: The culture approach maintained cell viability, preserved cell populations of all fetal adrenal zones, and recapitulated de novo adrenal steroidogenesis based on continued secretion of steroidogenic intermediates, glucocorticoids, and androgens. Adrenocorticotropic hormone and ketoconazole treatment of ex vivo cultured human fetal adrenal tissue resulted in the stimulation of steroidogenesis and inhibition of androgen secretion, respectively, demonstrating a treatment-specific response. Conclusions: Together, these data indicate that ex vivo culture of human fetal adrenal tissue constitutes a novel approach to investigate local effects of pharmaceutical exposures or emerging therapeutic options targeting imbalanced steroidogenesis in adrenal disorders, including CAH.

AB - Context: Disorders affecting adrenal steroidogenesis promote an imbalance in the normally tightly controlled secretion of mineralocorticoids, glucocorticoids, and androgens. This may lead to differences/disorders of sex development in the fetus, as seen in virilized girls with congenital adrenal hyperplasia (CAH). Despite the important endocrine function of human fetal adrenals, neither normal nor dysregulated adrenal steroidogenesis is understood in detail. Objective: Due to significant differences in adrenal steroidogenesis between human and model species (except higher primates), we aimed to establish a human fetal adrenal model that enables examination of both de novo and manipulated adrenal steroidogenesis. Design and Setting: Human adrenal tissue from 54 1st trimester fetuses were cultured ex vivo as intact tissue fragments for 7 or 14 days. Main Outcome Measures: Model validation included examination of postculture tissue morphology, viability, apoptosis, and quantification of steroid hormones secreted to the culture media measured by liquid chromatography-tandem mass spectrometry. Results: The culture approach maintained cell viability, preserved cell populations of all fetal adrenal zones, and recapitulated de novo adrenal steroidogenesis based on continued secretion of steroidogenic intermediates, glucocorticoids, and androgens. Adrenocorticotropic hormone and ketoconazole treatment of ex vivo cultured human fetal adrenal tissue resulted in the stimulation of steroidogenesis and inhibition of androgen secretion, respectively, demonstrating a treatment-specific response. Conclusions: Together, these data indicate that ex vivo culture of human fetal adrenal tissue constitutes a novel approach to investigate local effects of pharmaceutical exposures or emerging therapeutic options targeting imbalanced steroidogenesis in adrenal disorders, including CAH.

KW - ACTH

KW - androgen biosynthesis

KW - endocrine activity

KW - ex vivo culture

KW - ketoconazole

KW - steroidogenesis

U2 - 10.1210/clinem/dgaa852

DO - 10.1210/clinem/dgaa852

M3 - Journal article

C2 - 33212489

AN - SCOPUS:85102910589

VL - 106

SP - 843

EP - 857

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 3

ER -

ID: 282041325