Existence of Two Forms of Immunoreactive Growth Hormone in Human Plasma*

Samples of plasma from four patients with acromegaly, from two normal subjects following insulin-induced hypoglycemia, and from a patient with the syndrome of dwarfism and high plasma growth hormone (GH), were fractionated by gel filtration on Sephadex G-75, and immunoreactive GH (IRGH) was determined in the effluent fractions. In all seven samples, including four that were fractionated shortly after venipuncture, almost all of the IRGH in the effluent was found in two discrete peaks. In every instance the more retarded component (“little” IRGH) migrated almost identically with the major component of radioiodinated human pituitary GH, while “big” IRGH migrated at a rate consistent with a molecular size about twice that of “little” IRGH. “Big” IRGH constituted 14–28% of total effluent IRGH in the acromegalic patients, 25–28% in the normal subjects, and 23% in the dwarfed patient. On rechromatography of “little” IRGH and of freshly isolated “big” IRGH, there was no conversion of one component to the other. However, during storage at –20 C, more than half of isolated “big” IRGH was converted to a compound indistinguishable from “little” IRGH, suggesting that “big” IRGH consists of “little” IRGH bound to some dissociatable moiety. In the plasma of the normal subjects following hypoglycemia, “big” IRGH and “little” IRGH were each higher than total IRGH in these patients in the basal state, indicating that both components rose in response to hypoglycemia. Similarly, in two of the acromegalic patients, each of the two components was above the normal limit for total IRGH, indicating that both components may be increased in acromegaly. On gel filtration of a preparation of human pituitary GH, two discrete IRGH peaks were found which had migration characteristics indistinguishable from those of “big” and “little” IRGH in plasma, suggesting that both plasma components may be secreted by the pituitary.