Role of IGFs in human prepubertal testis: differentiation of steroidogenic cells

E BERENSZTEIN; MS BAQUEDANO; C GONZALEZ; SARACO; M SCIARA; R PONCIO; MA RIVAROLA; A BELGOROSKY

Helsinki, Finlandia

Congreso; 46th Annual Meeting of the European Society for Peadiatric Endocrinology (ESPE); 2007

European Society for Paediatric Endocrinology (ESPE)

The role of IGFs has been demonstrated mainly in rodents in testicular growth and development, control of Leydig cell (LC) number and in the onset ofsteroidogenesis. In human immature testis the information available is scarce. In this study, the role of the GH/IGF system in post natal testicularactivation was analyzed. Testes were collected from necropsies, following Hospital rules. For testicular immunochemistry, subjects of 3 age groups (Gr)were studied: Gr1 (n=11), neonatal (1- to 21-day-old newborns), Gr2 (n=13), postnatal testicular activation (1- to 7-month-old infants) and Gr3 (n=10),early prepuberty (12- to 36-month-old children). IGF1, IGF2, type 1IGF receptor (IGFR), insulin receptor (IR) and GHR immunoexpression was analyzed.IGF1 was barely detectable in interstitial cells (IC) and LC in all age groups. Strong immunostaining of IGF2 was detected in LC of Gr1 and Gr2.Moderate staining of IGFR was observed. Strong staining of IR was found in LC of Gr2 and moderate staining in IC of the 3 Grs. Moderate staining ofGHR was observed in LC of Gr2. In 6-day somatic testicular cell cultures of the 3 Grs, and in the absence of hCG or LH, IGF1 stimulated testosteronesecretion in pmol/d . million cells (mean ±SEM 400 ± 58.9 % of basal condition, n=23, p=0.011, t test). P450scc expression (% positive cells) was alsostimulated under IGF1 (1440 ± 405 % of basal, n=4, p=0.049). IGF1 stimulated cell proliferation index (203 ± 11.0 % of basal, n=4, p=0.007) andinhibited cell apoptotic index (43.8 ± 4.66 % of basal, n=15, p=0.021). These results provide the first evidence that the GH-IGFs system, mainly IGF2 viaIR, might be one of the factors involved in the induction of infantile LC differentiation. GH might act only in Gr2. In vitro studies showed that IGFsregulate immature cell proliferation and apoptosis, as well as steroidogenesis. We propose that during the testicular activation of infancy, the GH-IGFsaxis is involved differentiating immature LC pool and it prepares the infant testis for optimal response to stimulation by LH and testosterone secretion.