PubMed · 4863451
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U Kosmala, S Kwiatkowski. 1967. [Somatotropin].. https://pubmed.ncbi.nlm.nih.gov/4863451/
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CONTEXT: Experimental studies suggest that GH treatment may improve cardiovascular parameters in chronic heart failure (CHF). However, clinical trials involved small numbers of patients and did not allow a conclusion to be drawn on the effect of this treatment in humans. OBJECTIVE: We systematically reviewed and analyzed all randomized controlled trials and open studies of sustained GH treatment in CHF. STUDY SELECTION: Twelve trials were identified in three databases. We conducted a combined analysis of GH effects on cardiovascular parameters using the overall effect size to evaluate significance and computing the weighted mean differences with and without treatment to assess effect size. DATA SYNTHESIS: GH treatment significantly modified morphological cardiovascular parameters [interventricular septum thickness, +0.55 (sd, 0.43) mm (P < 0.001); posterior wall thickness, +1.01 (0.44) mm (P < 0.01); left ventricle (LV) end-diastolic diameter, -2.02 (1.22) mm (P < 0.01); and LV end-systolic diameter, -5.30 (2.33) mm (P < 0.05)]; LV and systemic hemodynamics [LV end-systolic wall stress, -38.9 (13.3) dynes/cm(2) (P < 0.001); LV ejection fraction, +5.10 (1.74)% (P < 0.05); and systemic vascular resistance, +195.0 (204.5) dyn x sec(-1) x cm(-5) (P < 0.01)]; and functional parameters [New York Heart Association class, -0.97 (0.23) (P < 0.01); exercise duration, +103.7 (37.6) sec (P < 0.001); and maximal oxygen uptake, +2.48 (1.76) ml/kg x min (P < 0.01)]. Subgroup analysis and meta-regression showed significant relationships between the IGF-I response and GH treatment effects. CONCLUSION: Our meta-analysis suggests that GH treatment improves several relevant cardiovascular parameters in patients with CHF. However, these results must be confirmed by a large randomized placebo-controlled trial on hemodynamic, morphological, and functional parameters during long-term high-dose GH treatment of patients with CHF.
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Growth hormone releasing hormone is one of the hormones secreted by the hypothalamus. Because of its potential applications in agriculture and medicine, its short half-life and its expensive chemical synthesis, an analog with high GHRH activity and prolonged half-life has been looked for. The fusion partner gene with 127 amino acid residues of the C-terminus from L-asparaginase was recombined respectively with asp-pro-pro-hGHRH(1-44), asp-pro-hGHRH(1-44) or asp-1pro-GHRH(2-44) genes synthesized by PCR method to form three kinds of fusion proteins with unique acid labile linker Asp-Pro. The Pro-Pro-hGHRH(1-44), Pro-hGHRH(1-44), and 1Pro-GHRH(2-44) peptides were purified to homogeneity by means of cell disruption, washing of inclusion body, ethanol fraction precipitation, acid hydrolysis, SP-Sephadex C-25 and Sephadex G-10 column chromatography. The peptide molecular mass of 5235, 5139 or 4975 Da was determined by ESI mass spectroscopy and purity was determined by SDS-PAGE. In the study of in vitro activity, the antiserum kit against human GH and peptide doses of 0.1, 1.0 and 10 microg/ml were used. These peptides obviously increased GH releases both from human pituitary and from rat pituitary. The activity comparisons showed that there was significant difference between Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys and Pro-Pro-hGHRH(1-44) at 1.0 microg/ml, or between 1Pro-hGHRH(2-44) and Pro-Pro-hGHRH(1-44) or Pro-hGHRH(1-44) at 10 microg/ml. The structure-activity relationships showed that at the original C-terminus, for rat pituitary the activity of the GHRH analog with 1Tyr-->Pro was more than that of Pro-Pro-hGHRH(1-44) or Pro-hGHRH(1-44). The results showed that the analogs had good GH-releasing activity and species specificity.