Titre
Insulin and IGF1 receptors are essential for the development and steroidogenic function of adult Leydig cells.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Neirijnck, Y.
Auteure/Auteur
Calvel, P.
Auteure/Auteur
Kilcoyne, K.R.
Auteure/Auteur
Kühne, F.
Auteure/Auteur
Stévant, I.
Auteure/Auteur
Griffeth, R.J.
Auteure/Auteur
Pitetti, J.L.
Auteure/Auteur
Andric, S.A.
Auteure/Auteur
Hu, M.C.
Auteure/Auteur
Pralong, F.
Auteure/Auteur
Smith, L.B.
Auteure/Auteur
Nef, S.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1530-6860
Statut éditorial
Publié
Date de publication
2018-06
Volume
32
Numéro
6
Première page
3321
Dernière page/numéro d’article
3335
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
The insulin family of growth factors (insulin, IGF1, and IGF2) are critical in sex determination, adrenal differentiation, and testicular function. Notably, the IGF system has been reported to mediate the proliferation of steroidogenic cells. However, the precise role and contribution of the membrane receptors mediating those effects, namely, insulin receptor (INSR) and type-I insulin-like growth factor receptor (IGF1R), have not, to our knowledge, been investigated. We show here that specific deletion of both Insr and Igf1r in steroidogenic cells in mice leads to severe alterations of adrenocortical and testicular development. Double-mutant mice display drastic size reduction of both adrenocortex and testes, with impaired corticosterone, testosterone, and sperm production. Detailed developmental analysis of the testes revealed that fetal Leydig cell (LC) function is normal, but there is a failure of adult LC maturation and steroidogenic function associated with accumulation of progenitor LCs (PLCs). Cell-lineage tracing revealed PLC enrichment is secondary to Insr and Igf1r deletion in differentiated adult LCs, suggesting a feedback mechanism between cells at different steps of differentiation. Taken together, these data reveal the cell-autonomous and nonautonomous roles of the IGF system for proper development and maintenance of steroidogenic lineages.-Neirijnck, Y., Calvel, P., Kilcoyne, K. R., Kühne, F., Stévant, I., Griffeth, R. J., Pitetti, J.-L., Andric, S. A., Hu, M.-C., Pralong, F., Smith, L. B., Nef, S. Insulin and IGF1 receptors are essential for the development and steroidogenic function of adult Leydig cells.
Sujets
PID Serval
serval:BIB_69B3EDFEA2DC
PMID
Date de création
2018-02-08T17:10:12.606Z
Date de création dans IRIS
2025-05-20T21:23:01Z