ABSTRACT IGF-1 is one of the major autocrine/paracrine factors for Leydig cell function in testes where it plays an important role in Leydig cell differentiation and maturation as well as in steroidogene sis. We assessed the effect of IGF-1 gene deletion on Leydig cell function by studying androgen synthesis in IGF-1 knockout mice (IGF-1 KO), and the impact, if any, on 17 β-HSD enzyme activity that is essential for the conversion of androstenedione (A) to testosterone (T). We also looked at how in vivo treatment with IGF-1 affected Leydig cell steroidogenic function in these null mutants. A Leydig cell fraction which also contained other interstitial cells (CRUDE Leydig cells), and another obtained by further purifying the crude fraction on percoll gradient (PURE Leydig cells) were used in this study. Basal and post-hCG levels of testosterone (T) and androstenedione (A) were measured by RIA. We found that both basal and hCG stimulated production of T and A were reduced in IGF-1 KO mice in comparison to wild type. On treatment of null mutants with IGF-1 in vivo, hCG stimulated T secretion was fully restored. Conclusion: IGF-1 does play a major role in controlling Leydig cell function. In its absence, as in the null mutants, reduced T production is observed. This does not appear to be due to any 17 β-HSD activity impairment.
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