Insulin and IGF1 receptors are essential for the development and steroidogenic function of adult Leydig cells

Autor: Richard J. Griffeth, Isabelle Stévant, François P. Pralong, Jean-Luc Pitetti, Françoise Kühne, Meng-Chun Hu, Silvana A. Andric, Yasmine Neirijnck, Lee B. Smith, Serge Nef, Karen R. Kilcoyne, Pierre Calvel
Přispěvatelé: Université de Genève (UNIGE), Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), University of Edinburgh, University of Novi Sad, National Taiwan University, Department of Internal Medicine, University Hospital, School of Environmental and Life Sciences, Newcastle University [Newcastle]
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
steroidogenesis
medicine.medical_treatment
Cellular differentiation
[SDV]Life Sciences [q-bio]
MOUSE
Biochemistry
testis development
Mice
0302 clinical medicine
ddc:576.5
Testosterone
Receptor
Mice
Knockout
TRANSGENIC MICE
Leydig cell
TESTIS
Stem Cells
PROLIFERATION
Leydig Cells
Cell Differentiation
ADRENAL-GLAND
medicine.anatomical_structure
DIFFERENTIATION
Biotechnology
EXPRESSION
medicine.medical_specialty
endocrine system
Biology
MATURATION
03 medical and health sciences
Growth factor receptor
progenitor Leydig cells
Internal medicine
GROWTH-FACTOR-I
Genetics
medicine
Animals
IGF
Molecular Biology
Insulin-like growth factor 1 receptor
adrenal gland
[SDV.GEN]Life Sciences [q-bio]/Genetics
Insulin
Receptors
Somatomedin
Receptor
Insulin
Insulin receptor
[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics
030104 developmental biology
Endocrinology
PROGENITOR CELLS
biology.protein
Adrenal Cortex
Corticosterone
030217 neurology & neurosurgery
Zdroj: FASEB Journal
FASEB Journal, Federation of American Society of Experimental Biology, 2018, 32 (6), pp.3321-3335. ⟨10.1096/fj.201700769RR⟩
FASEB Journal, Vol. 32, No 6 (2018) pp. 3321-3335
ISSN: 0892-6638
1530-6860
DOI: 10.1096/fj.201700769RR
Popis: 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.
Databáze: OpenAIRE
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