Physiopathology of human adrenocortical tumors (ACT): IGF receptor 1 and insulin receptor might be involved in tumor growth, while estrogens might regulate the steroidogenic pattern

MARIA SONIA BAQUEDANO; GABRIELA GUERCIO ; MARIANA COSTANZO; NORA SARACO; ESPERANZA BERENSZTEIN; MARIA T DE DAVILA; MARCO A RIVAROLA; ALICIA BELGOROSKY

Helsinki, Finlandia

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

European Society for Paediatric Endocrinology (ESPE)

Estrogens, produced locally in adrenal medulla, could play a role in zona reticularis functional differentiation through estrogen receptor â (ERâ) (Baquedano et al JCEM,2007), whereas the IGF system could be involved in postnatal proliferation and migration of progenitor adrenal cells (Baquedano et al Ped Res 2005). The IGF system coul be involved in ACT progression via type 1 IGF receptor (IGFR1). We analyzed aromatase (ARO), ERâ, insulin receptor (IR) A and B, IGF1, IGF2 and IGFR1 mRNA expression in 8 virilizing ACT of prepubertal children (age range 1.3-4.5 yr) and in 29 normal human adrenal tissues (HAT) (GR1, preadrenarche, GR2, post adrenarche). ACT mRNA levels of ARO (1.48±0.24 AU) and ERâ (1.43 ±0.38) were similar to GR2 but higher (p<0.05) than in GR1 (1.03±0.43 and 0.79±0.28, respectively). IRA (1.93±0.34) and IRB (1.39±0.28) were higher (p<0.05) than in GR1 and GR2 (1.19±0.44 and 1.34±0.35, 0.52±0.50 and 0.86±0.43, respectively). IGF1 (0.68±0.34) was lower (p<0.05) than in GR1 (1.26±0.42) but similar to GR2, while IGF2 (1.38±0.21) was similar to GR1 and GR2. IGFR1 (2.14±0.43) was higher than in GR1 (1.43±0.4, p<0.05). Significant positive correlation between tumor weight (as a parameter of malignancy) and IGFR1 (slope 358, r=0.87, p=0.01) or IRB (slope 484, r=0.75, p=0.029) was found, but the slope of the latter was higher, p<0.001. In ACT, different patterns of utilization of exons 1 were observed, but in contrast to HAT in the majority of ACT the adipose tissue promoter was prevalent. In conclusion we propose that similar to normal HAT, local estrogen production in ACT might play a role in androgen production. In ACT the expression of ARO might be regulated differently. Since cytokines regulate ARO adipose tissue promoter, they might also control ACT steroidogenesis pattern. The signaling activation of IGFR1 and IR might be involved in tumor growth.