Establishment of a novel human fetal adrenal culture model that supports de novo and manipulated steroidogenesis
C Melau, JE Nielsen, S Perlman… - The Journal of …, 2021 - academic.oup.com
C Melau, JE Nielsen, S Perlman, L Lundvall, L Langhoff Thuesen, K Juul Hare…
The Journal of Clinical Endocrinology & Metabolism, 2021•academic.oup.comContext 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 …
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 …
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.
Oxford University Press