Connective Tissue Activation. XXII. A Platelet Growth Factor (Connective Tissue-Activating Peptide-III) in Human Growth Hormone-Deficient Patients*

Abstract

Connective tissue-activating peptides (CTAPs) stimulate human synovial cells to exhibit a higher rate of DNA synthesis, glycolysis, and glycosaminoglycan formation. These bioactive peptides have been isolated from human platelets (CTAP-III), lymphocytes, tumor cells, and neutrophilic leukocytes. Several other growth factors, such as somatomedins A and C and nonsuppressible insulin-like activity (soluble), have been shown to be dependent on the circulating levels of pituitary GH. In this study, we examined the human GH (hGH) dependence of CTAP-III. Platelets from children with reduced or absent hGH were examined for the presence of CTAP-III. The peptide was detected qualitatively by polyacrylamide gel electrophoresis and Ouchterlony double diffusion. CTAP-III antigen, measured by RIA, was found in normal amounts in platelet lysates from normal persons and GH-deficient patients. Biological activity of the peptide was suggested by the ability of platelet lysates to stimulate the formation of glycosaminoglycans and increase sulfate incorporation into glycosaminoglycans formed in cell cultures. In addition, normal and hGH-deficient platelet lysates contained potent mitogenic activity which increased thymidine incorporation into DNA. Platelets from GH-deficient patients also released CTAP-III normally on exposure to thrombin.

The Isolation and Activity of Growth-Stimulating Factors from Human Platelets

“…In the absence of these inhibitors, the factor is degraded by cell or tissue proteases to ß-thromboglobulin, which is inactive äs a stimulator. A similar degradation of connective tissue activating peptide III has been discussed by Castor (22). In vivo, especially in plasma, the proteases appear to function by limiting the effect of the platelet growth factor, thereby counteracting any excess release of the factor.…”

Structural and biological characteristics of connective tissue activating peptide (CTAP-III), a major human platelet-derived growth factor.

“…In addition to mitogenic properties, some biologically active platelet factors were found to stimulate extracellular matrix (glycosaminoglycan) synthesis (3)(4)(5)(6)14 CTAP-III isolated from outdated human platelets was shown to share amino acid compositional, electrophoretic, and antigenic properties with -TG (6). The biological activities demonstrated for CTAP-III included stimulation of DNA, hyaluronic acid, and sulfated GAG synthesis, stimulation of glycolysis, prostaglandin E2 secretion, and intracellular cAMP accumulation (5,6,(17)(18)(19).…”

Heberden Oration 1980: aspects of the cell biology of the rheumatoid synovial lesion.

“…There are several other reports documenting suppression of cell proliferation in different cells which can be ascribed to prostaglandins.81-85 It is likely that the prostaglandin-induced increases in intracellular cAMP content account for these effects on growth.8i6 87 MCF itself does not produce acute increases in cAMP content of synovial cells but levels of the cyclic nucleotide do rise after several hours of exposure, which can be accounted for by increases in medium PGE2 levels resulting from cellular synthesis.35 These observations are similar to those reported earlier by Castor et al67 using preparations of connective tissue activating peptides (CTAPs) which also stimulate prostaglandin synthesis. The CTAPs are extracted from different cells such as platelets, lymphocytes, tumour cells and neutrophilic leucocytes 88. The chemical and biological relationship of the CTAPs to MCF has not yet been determined, however.…”