Strong Immunoexpression of IGF-2 and the Insulin Receptor in Leydig and Germ Cells of the Human Postnatal testis

ESPERANZA B. BERENSZTEIN; CANDELA R. GONZALEZ; ROBERTO PONZIO; NORA I. SARACO; MARCO A. RIVAROLA; ALICIA BELGOROSKY

Boston, Estados Unidos

Congreso; The Endocrine Society´s 88th Annual Meeting; 2006

The Endocrine Society

Strong Immunoexpression of IGF-2 and the Insulin Receptor in Leydig and Germ Cells of the Human Postnatal Testis. Esperanza Berensztein, Candela Gonzalez, Roberto Ponzio, Nora Saraco, Marco A Rivarola, Alicia Belgorosky. Res Lab, Garrahan Pediat Hosp., Buenos Aires, Argentina; Ctr de Invest en Reprod, Univ de Buenos Aires, Buenos Aires, Argentina. Small testes have been described in isolated GH deficiency or GH insensitivity, as well as in IUGR patients. It has been proposed that IGFs might be involved in Leydig cell (LC) proliferation and function in rodents and pigs. The hypothesis of this study is that the GH/IGF axis in involved in the functional differentiation of LC precursors, as well as in the maintenance of the immature germ cell (GC) pool, gonocytes and spermatogonia, in infants. Three age groups (Gr) were defined: Gr1 (n=11), neonatal (1- to 21-day-old newborns), Gr2 (n=11), postnatal testicular activation (1- to 7-month-old infants) and Gr3 (n=10), early prepuberty (12- to 36-month-old children). IGF1, IGF2, IGFR, insulin receptor (IR) and GHR immunoexpression was analyzed in testes collected at necropsy. Results. In interstitial cells (IC), low expression (< 5%) of IGF1 and GHR, and moderate expression of IR (5-15%), was observes in all Grs. However, IGF2 expression was higher in Gr1 than in Gr2 or Gr3 (7.0±1.3 vs 4.8±2.4 and 3.5±2.5 %). IGFR expression as higher in Gr1 and Gr2 than in Gr3 (11.7±4.5, 7.2±2.9 and 2.8±0.8%, respectively p=0.046). In LC, the expression of IHF1 in Gr1 and Gr2 was undetectable, but IGF2 was high (33 and 44.8%) and IGFR moderate (8.6 and 4.4%) in Gr1 and Gr2. IR was moderate (8.0%) in Gr1, but increased in Gr2 (36.7%). Interestingly, GHR was only found in LC of Gr2 (13.7%). In peritubular (PC) and in Sertoli cells (SC), vry low expression of IGF1, IGF2, IGFR1, GHR and IR was found in all Grs. In GC of the 3 Grs, IGF1 was moderately expressed while a strong label of IGF2, IGFR1 and IR was found. In testicular cell cultures, rhGH significantly increased T secretion in 4/8 cultures of Gr2 (range: 153-8000% of basal). However, IGF1 stimulated T secretion in all Grs (287±245% of basal, n=13). In conclusion, in LC of Gr1, local IGF2 acting through IGFR or IR might modulate LC steroidogenesis, before the LH peak. In Gr2, serum GH through GHR might modulate IGF2 production of LC. Since IR clearly increased in LC of Gr2, we propose that IGF2, mainly through type A IR, might be involved in functional LC differentiation and potentiation of gonadotropin action. In some IC, probably LC precursors, IGF2 could be involved, among other factors, in the stimulation of cell proliferation and/or inhibition of cell apoptosis, mainly in Gr1. In addition, local production of IGFs in GC might suggest an autocrine role of IGFs to preserve spermatogonia in human prepubertal testis.