Subject(s)
Growth Hormone-Releasing Hormone/physiology , Growth Hormone/metabolism , Pituitary Gland, Anterior/metabolism , Acromegaly/metabolism , Amino Acid Sequence , Animals , Binding Sites , Cats , Cattle , Chemical Phenomena , Chemistry , Cyclic AMP/biosynthesis , Diabetes Mellitus/metabolism , Gestational Age , Growth Hormone/biosynthesis , Growth Hormone/deficiency , Growth Hormone-Releasing Hormone/isolation & purification , Growth Hormone-Releasing Hormone/pharmacology , Haplorhini , Hormones, Ectopic/analysis , Humans , Hypothalamus/metabolism , Kinetics , Rats , Species SpecificityABSTRACT
Human hypothalamic growth hormone-releasing factor (GRF) was purified by gel filtration and reverse-phase HPLC. Bioassay and two radioimmunoassays of different specificity revealed the presence of two major forms of GRF-activity which coelute with human pancreas GRFs, hpGRF-44-NH2 and hpGRF-40 previously characterized in pancreas tumors. The bioactive material coeluting with hpGRF-44-NH2 is recognized by two antibodies which are directed against the amidated COOH-terminal sequence and the central portion of the GRF-44 peptide. The bioactive GRF which coelutes with hpGRF-40 reacts only with the antibody directed against the central portion of hpGRF. These data strongly suggest that the human hypothalamus contains the same major forms of GRF that were identified in pancreas tumors responsible for acromegaly in the absence of a pituitary tumor.
Subject(s)
Growth Hormone-Releasing Hormone/analysis , Hypothalamus/analysis , Biological Assay , Female , Growth Hormone-Releasing Hormone/pharmacology , Hormones, Ectopic/analysis , Humans , Male , Molecular Weight , Pancreatic Neoplasms/analysis , Protein Processing, Post-Translational , Radioimmunoassay , Structure-Activity RelationshipABSTRACT
Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.