RGD Reference Report - Insulin-like growth factor-I is an important antiapoptotic factor for rat leydig cells during postnatal development. - Rat Genome Database

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Insulin-like growth factor-I is an important antiapoptotic factor for rat leydig cells during postnatal development.

Authors: Colon, E  Zaman, F  Axelson, M  Larsson, O  Carlsson-Skwirut, C  Svechnikov, KV  Soder, O 
Citation: Colon E, etal., Endocrinology. 2007 Jan;148(1):128-39. Epub 2006 Oct 5.
RGD ID: 1600072
Pubmed: PMID:17023532   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2006-0835   (Journal Full-text)

The present investigation examines the influence of IGF-I and the role of IGF-I receptor (IGF-IR) in the apoptosis/survival of Leydig cells. Immunohistochemical analysis of the rat testis at different ages revealed that the level of the phosphorylated IGF-IR increases from birth to d 20 of postnatal life, remaining high in the adult testis. Western blotting revealed that this level is higher in Leydig cells isolated from 40-d-old than from 10- or 60-d-old rats. Application of the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay revealed that IGF-I decreases the level of apoptosis in Leydig cells at all stages of development, and the selective inhibitor of IGF-IR, picropodophyllin, blocks this antiapoptotic effect. The mechanism underlying the antiapoptotic action of IGF-I involves the phosphatidylinositol 3-kinase/Akt pathway, and in immature Leydig cells, this growth factor enhances the expression of Bcl-2 and cellular inhibitor of apoptosis proteins 2, while preventing activation of caspase-3 by cleavage. Furthermore, IGF-II and high concentrations of insulin also evoke phosphorylation of IGF-IR and, like IGF-I, enhance the expression of the steroidogenic acute regulatory protein by Leydig cells. Inhibition of IGF-IR by picropodophyllin decreases the survival of Leydig cells, both in the presence and absence of IGF-I, demonstrating that signaling via the IGF-IR plays an important role in Leydig cell survival.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein serine/threonine kinase activator activity enablesIDA 1600072PMID:17023532BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Gh1  (growth hormone 1)
Igf1  (insulin-like growth factor 1)
Igf1r  (insulin-like growth factor 1 receptor)
Igf2  (insulin-like growth factor 2)
Star  (steroidogenic acute regulatory protein)


Additional Information