title: An essential role for insulin and IGF1 receptors in regulating sertoli cell proliferation, testis size, and FSH action in mice.
abstract: Testis size and sperm production are directly correlated to the total number of adult Sertoli cells (SCs). Although the establishment of an adequate number of SCs is crucial for future male fertility, the identification and characterization of the factors regulating SC survival, proliferation, and maturation remain incomplete. To investigate whether the IGF system is required for germ cell (GC) and SC development and function, we inactivated the insulin receptor (Insr), the IGF1 receptor (Igf1r), or both receptors specifically in the GC lineage or in SCs. Whereas ablation of insulin/IGF signaling appears dispensable for GCs and spermatogenesis, adult testes of mice lacking both Insr and Igf1r in SCs (SC-Insr;Igf1r) displayed a 75% reduction in testis size and daily sperm production as a result of a reduced proliferation rate of immature SCs during the late fetal and early neonatal testicular period. In addition, in vivo analyses revealed that FSH requires the insulin/IGF signaling pathway to mediate its proliferative effects on immature SCs. Collectively, these results emphasize the essential role played by growth factors of the insulin family in regulating the final number of SCs, testis size, and daily sperm output. They also indicate that the insulin/IGF signaling pathway is required for FSH-mediated SC proliferation.
authors.affiliation: Department of Genetic Medicine and Development, National Center of Competence in Research, Frontiers in Genetics, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pitetti
authors.forename: Pierre
authors.initials: P
authors.lastname: Calvel
authors.forename: Céline
authors.initials: C
authors.lastname: Zimmermann
authors.forename: Béatrice
authors.initials: B
authors.lastname: Conne
authors.forename: Marilena D
authors.initials: MD
authors.lastname: Papaioannou
authors.forename: Florence
authors.initials: F
authors.lastname: Aubry
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cederroth
authors.forename: Françoise
authors.initials: F
authors.lastname: Urner
authors.forename: Betty
authors.initials: B
authors.lastname: Fumel
authors.forename: Michel
authors.initials: M
authors.lastname: Crausaz
authors.forename: Mylène
authors.initials: M
authors.lastname: Docquier
authors.forename: Pedro Luis
authors.initials: PL
authors.lastname: Herrera
authors.forename: François
authors.initials: F
authors.lastname: Pralong
authors.forename: Marc
authors.initials: M
authors.lastname: Germond
authors.forename: Florian
authors.initials: F
authors.lastname: Guillou
authors.forename: Bernard
authors.initials: B
authors.lastname: Jégou
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D048430:Cell Shape / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000166:cytology / Q000196:embryology; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D020869:Gene Expression Profiling; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D012671:Seminiferous Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000494:pharmacology
chemical_list: D013963:Thyroid Hormones; D005640:Follicle Stimulating Hormone; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt