INCREASED EXPRESSION OF GROWTH-HORMONE RECEPTOR MESSENGER-RNA AND INSULIN-LIKE GROWTH-FACTOR-I MESSENGER-RNA IN VOLUME-OVERLOADED HEARTS

Recent results suggest that insulin-like growth factor-I (IGF-I) may be involved in the transition of a hemodynamic load into cardiac hypertrophy and that the expression of IGF-I seems to be coupled to increased wall stress. The present study investigated the role of growth hormone (GH) and IGF-I in myocardial hypertrophy induced by volume overload. An aortocaval fistula (ACF) was created in male Wistar rats, and experiments were performed 2, 4, and 7 days after the onset of volume overload. Right and left ventricular (RV and LV, respectively) myocardial expression of GH receptor mRNA and IGF-I mRNA were quantitated by a solution hybridization RNase protection assay. RV GH receptor mRNA content was elevated on the fourth and seventh days after the induction of the shunt, with peak levels (0.63+/-0.16 versus 0.14+/-0.03 amol/mu g DNA for the sham-operated animals; P<.01) after 4 days. Similarly, IGF-I mRNA was significantly increased in the RV of shunted animals (1.26+/-0.13 versus 0.56+/-0.05 amol/mu g DNA; P<.01) 7 days after surgery. In the left ventricle, where systolic pressure was reduced in ACF rats, no differences could be detected in GH receptor and IGF-I mRNA content between ACF and sham-operated rats on any of the experimental days. There was no difference in the ratio of RV to LV weight during the experimental period. We have shown that the thin-walled right ventricle responds to volume overload with an increase of GH receptor mRNA content followed by elevated expression of IGF-I mRNA. The present results suggest that the heart regionally produces trophically acting factors, such as IGF-I, which may be of importance for the initiation of the hypertrophic process, at least when a ventricle is being challenged, such as the right ventricle in volume overload.