Growth hormone (GH) JAK2/STAT5 signaling during the growth period in liver of mice overexpressing GH

MARTINEZ CS; PIAZZA VG; DÍAZ ME; BOPARAI RK; ARUM O; RAMÍREZ MC; GONZÁLEZ L; BECÚ-VILLALOBOS D; BARTKE A; TURYN D; MIQUET JG; SOTELO AI

JOURNAL OF MOLECULAR ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2015 vol. 54 p. 171 - 184

0952-5041

GH/STAT5 signaling is desensitized in the liver of adult transgenic mice overexpressing GH; however, these animals present greater body size. To assess whether the STAT5 pathway is active during the growth period in the liver of these animals, and how signaling modulators participate in this process, growing transgenic mice and normal siblings were evaluated. STAT5 does not respond to an acute GH-stimulus, but presents higher basal phosphorylation in the liver of growing GH-overexpressing mice. GH receptor and positive modulators glucocorticoid receptor and HNF1 display greater abundance in transgenic animals, supporting STAT5 activity. Negative modulators cytokine-induced suppressor and PTP1B are increased in GH-overexpressing mice. The suppressors SOCS2 and SOCS3 exhibit higher mRNA levels in transgenic mice but lower protein content, suggesting that they are being actively degraded. Therefore, STAT5 signaling is increased in liver of GH-transgenic mice during the growth period, with a balance between positive and negative effectors resulting in an accelerated but controlled growth.