An Essential Role for Insulin and IGF1 Receptors in Regulating Sertoli Cell Proliferation, Testis Size, and FSH Action in Mice

Mol Endocrinol. 2013 May;27(5):814-27. doi: 10.1210/me.2012-1258. Epub 2013 Mar 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Cell Shape / drug effects
  • Female
  • Fetus / cytology
  • Fetus / embryology
  • Follicle Stimulating Hormone / metabolism*
  • Gene Expression Profiling
  • Germ Cells / cytology
  • Germ Cells / drug effects
  • Germ Cells / metabolism
  • Humans
  • Leydig Cells / cytology
  • Leydig Cells / drug effects
  • Leydig Cells / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation / genetics
  • Organ Size / drug effects
  • Organ Size / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism*
  • Seminiferous Tubules / cytology
  • Seminiferous Tubules / drug effects
  • Seminiferous Tubules / metabolism
  • Sertoli Cells / cytology*
  • Sertoli Cells / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Spermatogenesis / drug effects
  • Spermatogenesis / genetics
  • Spermatozoa / cytology
  • Spermatozoa / drug effects
  • Spermatozoa / metabolism
  • Thyroid Hormones / pharmacology

Substances

  • Thyroid Hormones
  • Follicle Stimulating Hormone
  • Receptor, IGF Type 1
  • Receptor, Insulin
  • Proto-Oncogene Proteins c-akt