Potential role of glucocorticoid signaling in the formation of pancreatic islets in the human fetus.
Glucocorticoids have been suggested to play a role in programming late adult disorders like diabetes during fetal life. Recent work in rodents showed their role in pancreas development by modulating the expression of transcription factors. The aim of this work was to investigate their possible implication in human pancreas development. The ontogenesis of glucocorticoid receptor (GR) and several pancreatic transcription factors was studied by immunohistochemistry and RT-PCR on human fetal pancreatic specimens. At 6 wk of development (wd) insulin promoting factor 1 (IPF1) was expressed in the majority of epithelial cells forming tubular structures while GR was present in the mesenchyme, suggesting an early role of glucocorticoids, before endocrine and exocrine differentiation. Only GR alpha (active form) mRNA was expressed from 6 wk onwards while GR beta (inactive form) was never observed. The first insulin cells did not express IPF1 or GR. Islet formation occurred from 10 wd as IPF1-positive cells started to express simultaneously insulin and GR. This coexpression in beta cells persisted until adulthood. The mRNA expression profiles confirmed immunohistochemistry and showed the early expression of crucial transcription factors. In conclusion, the presence of the active GR isoform around islet formation supports the novel idea that glucocorticoids could modulate human pancreas development.
INSERM, [Fetopathology Department, Université Denis Diderot-Paris 7, 75019 Paris, France.
Franziska
F
Phan-Hug
Fabien
F
Guimiot
Vincent
V
Lelièvre
Anne-Lise
AL
Delezoide
Paul
P
Czernichow
Bernadette
B
Breant
Bertrand
B
Blondeau
D017931:DNA Primers / Q000235:genetics; D005333:Fetus; D005938:Glucocorticoids / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000196:embryology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D017931:DNA Primers; D005938:Glucocorticoids; D018398:Homeodomain Proteins; D011965:Receptors, Glucocorticoid; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein