Insulin-like growth factors
(IGFs) are involved in cell metabolism, growth, differentiation, and survival
in most organs, including those of the reproductive axis. The activities of
these factors are regulated by a family of six high affinity-binding proteins
(IGFBP-1–6), which determine IGF bioavailability in circulating fluids and the
cellular environment.
IGFBP-3 is the most abundant
circulating IGF-binding protein and mediates IGF independent actions on cell
survival and apoptosis. In the testis, IGFs and IGFBPs are localized in the
same cells that express LH and FSH receptors. IGFBP-2 and -3 are the most
abundant IGFBPs in this organ and large amounts of IGFBP-3 are produced by
Sertoli and Leydig cells. Both FSH and (Bu)2cAMP markedly lower IGFBP-3 levels
in Sertoli cells and this binding protein can either inhibit or enhance the
effects on Leydig cells steroidogenesis depending on the surrounding
conditions.
The involvement of IGFBP-3 in steroidogenesis,
development, and tumor growth in the testis is poorly understood. Previous
investigations have revealed that IGFBP-3, -4, and -2 are predominantly
expressed by Leydig cells. It has been proposed that IGFBP-3 also potentiates
the inhibitory effects of cytokines on steroidogenesis. Both IGFBP-3 and -4
have been reported to be down-regulated in testicular seminomas, allowing more
rapid tumor growth.
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