Ames Dwarf (Prop1df/Prop1df) mice display increased sensitivity of the major GH-signaling pathways in liver and skeletal muscle

MIQUET JG; SOTELO AI; MUÑOZ MC; GIANI JF; GONZÁLEZ L; DOMINICI FP; BARTKE A,; TURYN D

Torino, Italia

Congreso; 1st Basic Postgraduate Course of the European Society for Endocrinology: Endocrinology meets Science; 2009

European Society for Endocrinology

ContributionGrowth hormone (GH) is an anabolic hormone that regulates growth and metabolism. Amesdwarf mice are natural mutants for Prop-1, with impaired development of anterior pituitaryand undetectable levels of circulating GH, prolactin and TSH. They constitute an endocrinemodel of life-long GH deficiency [1].The principal signaling cascades activated by GH binding to its receptor are theJAK2/STATs, PI-3K/Akt and the MAPK Erk 1/2 pathways [2]. We have previously reportedthat GH-induced STAT5 activation was higher in Ames dwarf mice liver, compared to nondwarfcontrols [3]. The aim of the present study was to evaluate the principal components ofthe main GH-signaling pathways in liver and skeletal muscle, another GH-target tissue, underGH-deficiency.Ames dwarf mice and their non-dwarf siblings were injected i.p. with GH or saline 15minutes before tissue removal. Protein content and phosphorylation of signaling mediatorswere determined by immunoblotting of tissue solubilizates.GH was able to induce STAT5 and STAT3 phosphorylation in both tissues, but the responsewas higher for Ames dwarf mice than for non-dwarf controls. GH-induced Aktphosphorylation at Ser473 in liver was only detected in dwarf mice, while both normal anddwarf mice responded to a GH stimulus in skeletal muscle, although dwarf mice presentedhigher GH activation levels. When Erk1/2 activation was assessed in liver, only dwarf miceshowed GH-induced phosphorylation, while in muscle no response to the hormone was foundin either genotype. Protein content of the signaling mediators studied did not vary betweennormal and dwarf animals in the evaluated tissues.The results show that for the main GH signaling pathways, Ames dwarf mice exhibitenhanced sensitivity to the hormone in liver and muscle.REFERENCE LIST[1] Bartke A, Brown-Borg. Life extension in the dwarf mice. Curr Top Dev Biol. 2004 63:189-225[2] Lanning NJ, Carter-Su C. Recent advances in growth hormone signaling. Rev Endocr Metab Disord. 2007 7:225-235[3] Miquet JG, Sotelo AI, Dominici FP, Bonkowski MS, Bartke A, Turyn D. Increased sensitivity to GH in liverof Ames dwarf (Prop1df/ Prop1df) mice related to diminished CIS abundance. J Endocrinol. 2005 187:387-397