RRC ID 49725
Author Matsuo K, Sone M, Honda-Kohmo K, Toyohara T, Sonoyama T, Taura D, Kojima K, Fukuda Y, Ohno Y, Inoue M, Ohta A, Osafune K, Nakao K, Inagaki N.
Title Significance of dopamine D1 receptor signalling for steroidogenic differentiation of human induced pluripotent stem cells.
Journal Sci Rep
Abstract Human induced pluripotent stem cells (hiPSCs) are expected to be both a revolutionary cell source for regenerative medicine and a powerful tool to investigate the molecular mechanisms underlying human cell development in vitro. In the present study, we tried to elucidate the steroidogenic differentiation processes using hiPSC-derived intermediate mesoderm (IM) that is known to be the origin of the human adrenal cortex and gonads. We first performed chemical screening to identify small molecules that induce steroidogenic differentiation of IM cells expressing Odd-skipped related 1 (OSR1), an early IM marker. We identified cabergoline as an inducer of 3β-hydroxysteroid dehydrogenase, an essential enzyme for adrenogonadal steroidogenesis. Although cabergoline is a potent dopamine D2 receptor agonist, additional experiments showed that cabergoline exerted effects as a low-affinity agonist of D1 receptors by increasing intracellular cyclic AMP. Further analysis of OSR1+ cells transfected with steroidogenic factor-1/adrenal 4 binding protein revealed that D1 receptor agonist upregulated expression of various steroidogenic enzymes and increased secretion of steroid hormones synergistically with adrenocorticotropic hormone. These results suggest the importance of dopamine D1 receptor signalling in steroidogenic differentiation, which contributes to effective induction of steroidogenic cells from hiPSCs.
Volume 7(1)
Pages 15120
Published 2017-11-9
DOI 10.1038/s41598-017-15485-4
PII 10.1038/s41598-017-15485-4
PMID 29123220
PMC PMC5680317
MeSH 3-Hydroxysteroid Dehydrogenases / metabolism Adrenal Cortex Hormones / metabolism Biomarkers / analysis Cabergoline / metabolism Cell Differentiation* Dopamine Agonists / metabolism Humans Induced Pluripotent Stem Cells / drug effects* Induced Pluripotent Stem Cells / physiology* Receptors, Dopamine D1 / metabolism* Signal Transduction* Transcription Factors / analysis
IF 3.998
Times Cited 0
DNA material pCMFlag_hsNR5A1 (RDB06299)