Actions of GRF in Man

Abstract

In 1980 we investigated a 21-year-old woman with Turner’s syndrome, acromegaly, and hyperprolactinemia (1). A head CT scan revealed an enlarged pituitary gland but no discreet pituitary adenoma was detected. It was assumed that she had a growth hormone-secreting adenoma and she subsequently underwent transsphenoidal surgery. After surgery she was not cured of her acromegaly. The surgical specimen was sent to Dr. Kalman Kovacs and he astutely diagnosed somatotroph hyperplasia and not a pituitary adenoma. At about this time, a paper by Dr. Frohman and colleagues appeared describing the partial characterization of a GH-releasing factor (GRF) from peripheral tumors which also caused acromegaly (2). Based on this information and the pituitary histology, a search was then made for an ectopic GRF source which may have resulted in somatotroph hyperplasia. A CT scan of the abdomen revealed a 5 cm tumor in the tail of the pancreas. The tumor was resected and preserved under ideal conditions for possible extraction, isolation and characterization of GRF. The bulk of the tumor was sent to Drs. Wylie Vale and Jean Rivier at the Salk Institute; portions were also sent to several other investigators in the hope of establishing a cell line which secreted GRF. Within a few weeks (September 1981) Vale and Rivier had demonstrated that this tumor contained a GRF peptide which had similar chromatographic characteristics to GRF activity from rat hypothalamic extract.