Molecular forms of circulating growth hormone during spontaneous secretory episodes and in the basal state

Abstract

After pharmacological stimulation of the pituitary gland, human GH (hGH) in plasma consists of three or more monomeric molecular forms and several corresponding oligomers. However, the chemical nature of hGH circulating under physiological (stimulated or basal) conditions is not known. In particular, the molecular basis for the GH-like bioactivity of plasma is poorly understood. To gain information on the type(s) of hGH normally found in blood, we extracted hGH from plasma obtained at the time of spontaneous secretory episodes (nocturnal and random release) and during basal periods in 15 normal subjects. Appropriate plasma volumes (30 or 300 ml) were extracted by immunoadsorbent chromatography, and the extracts were analyzed by native polyacrylamide gel electrophoresis at pH 7.5 and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at pH 10. The plasma hGH pattern at the time of spontaneous secretion was similar to that after pharmacological stimulation and consisted of 22K (principal), 20K, and acidic hGH as well as hGH dimer. In contrast, plasma hGH patterns during basal periods were highly variable and included immunoreactive hGH fragments in addition to the known hGH forms. Components with mol wt of 30K, 16K, and 12K were consistently identified. We conclude that 1) endogenously stimulated hGH secretion results in the same plasma hormone patterns as pharmacological stimuli; 2) several immunoreactive hGH fragments contribute to the heterogeneity of plasma hGH; and 3) hGH fragments may become a dominant part of total immunoreactivity in the basal state.