High P450 Aromatase (ARO) and Estrogen Receptor (ER) â Expression in Prepubertal Human Germ Cells (GC).

ESPERANZA B. BERENSZTEIN; MARÍA SONIA BAQUEDANO; JESICA ACCORINTI; MARIANA COSTANZO; CAROLINA M. PEPE; NORA I. SARACO; R PONZIO; MARCO A RIVAROLA; ALICIA BELGOROSKY

San Francisco, CA, USA

Congreso; The Endocrine Society's 90th Annual Meeting; 2008

The Endocrine Society

At least two steps of spermatogenesis seem to be in part regulated by estrogens, stem cell number and spermatid maturation (1). In men, ARO gene mutations lead to sterility (2). The stem cell factor secreted by Sertoli cells and its receptor c-kit, present in immature (i) GCs, play an important role in spermatogonial development. We have previously described an increment of the proliferation index and a decrement of apoptotic index, in the germ cells (GC) population of the neonatal human testis (HT) (3). Many factors could act on the preservation of the iGC pool. It is interesting that despite high levels of intratesticular testosterone during the postnatal activation period, spermatogenesis is not developed until puberty. The hypothesis is that local estrogens and IGFs act on the preservation of the iGC pool during prepuberty. Tissue from prepubertal HT was obtained at necropsy (n= 36) and divided into age-groups (Gr): Gr1, neonatal (<21-day-old), Gr2, postnatal activation (1- to 7-mo-old), and Gr3 prepuberty (1- to 9-y-old subjects). GC immunoexpression of c-kit, ERá, ERâ, ARO, IGF-1, IGF-2, type 1 IGF receptor (IGFR), and insulin receptor (IR) was studied. C-kit in Gr1 and Gr2 was higher than in Gr3, p<0.05 (Anova). No ERá was detected, while high ERâ expression was found in the three age Grs (47.8±21.9, 46.0±20.9 and 45.4±26.4 % of + cells, respectively, mean±SD). Similar to c-Kit, ARO expression in GC from Gr1 and Gr2 (45.2±25.5 and 45.4±22.3) was higher than in Gr3 (20.3±15 %), p<0.05. High IGF-2 (25.6± 3.1, 29.2± 7.1 and 28.3± 9.6 %) and IR (37.3±11.9, 41.4±11.3 and 50.8±6.5 %) expression and moderate IGF-1 (11.7±8.82, 7.28±7.06 and 7.07±3.62 %) and IGFR (7.7±5.5, 9.6±7.5 and 11.4±6.7 %) expression was observed in all Grs, without differences among them. These results suggest that 1) ARO is present in iGC producing high local levels of estrogens from the large intratesticular testosterone pool mainly during neonatal and postnatal activation periods, 2) Estrogens act on iGC through ERâ and 3) The temporal association with c-kit positive iGC suggests that estrogens, and not IGFs or insulin, might contribute to preserve the iGC pool during the period of spermatogonial proliferation and differentiation in the human.1. Carreau S, et al J Steroid Biochem Mol Biol. 2001 79:203-8. 2. Carani C, et al. N Engl J Med 1997 10;337:91-5.3. Berensztein E, et al. J Clin Endocrinol Metab. 2002 87:5113-8.