Chronic growth hormone hypersecretion induces reciprocal and reversible changes in mRNA levels from hypothalamic GH releasing hormone and somatostatin neurons

We studied papillary muscle mechanics and energetics, myosin phenotype, and ATPase activities in left ventricles from rats bearing a growth hormone (GH)-secreting tumor. 18 wk after tumor induction, animals exhibited a dramatic increase in body weight (+101 % vs. controls) but no change in the ventricular weight/body weight ratio. The maximum isometric force of papillary muscles normalized per cross-sectional area rose markedly (+42%, P < 0.05 vs. controls), whereas the maxi-mum unloaded shortening velocity did not change. This was observed despite a marked isomyosin shift towards V3 (32±5% vs. 8±2 % in controls, P < 0.001). Increased curvature of the force-velocity relationship (+64%, P < 0.05 vs. controls) indi-cated that the muscles contracted more economically, suggest-ing the involvement of V3 myosin. Total calcium- and actin-activated myosin ATPase activities assayed on quickly frozen left ventricular sections were similar in tumor-bearing rats and in controls. After alkaline preincubation, these activities only decreased in tumor-bearing rats, demonstrating that V3 enzy-matic sites were involved in total ATPase activity. These data demonstrate that chronicGH hypersecretion in the rat leads to a unique pattern of myocardial adaptation which allows the muscle to improve its contractile performance and economy simultaneously, thanks to myosin phenoconversion and an in-crease in the number of active enzymatic sites. (J. Clin. Invest