Inactivation of the IGF-I receptor gene in primary Sertoli cells highlights the autocrine effects of IGF-I.
IGF-I regulates pituitary and gonadal functions, and is pivotal for sexual development and fertility in mammalian species. To better understand the function of autocrine IGF-I in Sertoli cell physiology, we established a system for Cre-mediated conditional inactivation of the IGF-I receptor (IGF-IR) in cultured Sertoli cells. We show here that loss of IGF-IR decreased the number of viable Sertoli cells as a consequence of diminished Sertoli cell proliferation and increased Sertoli cell death. Furthermore, the lack of IGF-IR altered the morphology of cultured Sertoli cells and decreased lactate and transferrin secretions. Collectively, our data indicate that autocrine IGF-I contributes significantly to Sertoli cell homeostasis. The described in vitro system for loss-of-function analysis of the IGF-IR can be readily transposed to study the role of other intratesticular growth factors involved in spermatogenesis.
Froment
P
P
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Lyon F-69003, France. froment@lyon.inserm.fr
Vigier
M
M
Nègre
D
D
Fontaine
I
I
Beghelli
J
J
Cosset
F L
FL
Holzenberger
M
M
Durand
P
P
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival; D005818:Genetic Engineering; D015151:Immunoblotting; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis / Q000502:physiology*
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1