A Dialyzable Heat Stable Factor in Acromegalic Plasma Associated with Increased in Vitro Growth Hormone Release 1

A number of reports in the recent literature have suggested the possibility of persistent hypothalamic control in acromegaly (1-3), and further that a primary pathogenetic defect may be characterized by excessive secretion of hypothalamic growth hormone releasing factor. In a previous communication from this laboratory we have shown greater in vitro release of monkey pituitary growth hormone in the presence of acromegalic plasma than in the presence of normal plasma (4). It is the purpose of this report to further characterize this observation.

Methods Intact rhesus monkey pituitary glands were obtained and handled in a manner previously described (4). The incubation mixture of 10 ml included lactated ringers 7.5 ml, containing 50 μg/ml neomycin, and a glucose concentration of 100 mg/100 ml, to which 2.5 ml aliquots of plasma or dialysates of plasma with added albumin were added for study purposes. All incubations were carried out in a Dubnoff shaker at 37°, aliquots for immunoreactive growth hormone were obtained at 30 sec after the start of an incubation, during and at the conclusion of two hour incubation periods. Growth hormone was assayed using minor modifications of a solid phase radioimmunoassay (5), with highly specific rabbit anti-growth hormone antibodies, produced in our laboratory. The standard is purified human growth hormone, NIH HS-1147.

Three types of experiments were carried out. In one, whole pituitaries were incubated for 2 hr periods, first either in the presence of normal or acromegalic plasma, washed and transferred to a different plasma and then finally back to the original medium. Three intact glands were started first in acromegalic plasma, transferred to normal plasma and back for the final 2 hr of incubation to acromegalic palsma. Two pituitary glands were incubated in reverse order.