Growth Hormone Production by Human Pituitary Glands in Organ Culture: Evidence for Predominant Secretion of the Single-Chain 22,000 Molecular Weight Form (Isohormone B)*

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Abstract
Human GH (hGH) extracted from pituitary glands is known to consist of several molecular forms (isohor-mones). The predominant pituitary form is the 22,000 mol wt single-chain peptide (hGH-B), but several proteolytically cleaved 2-chain forms (hGH-C, D, and E) as well as a single-chain variant with a 15 amino acid deletion (20K) are also present. It is not known which of these forms is secreted. Since hGH-D and E exhibit substantially enhanced biological activity, it has been postulated that hGH may be proteolytically activated before or during secretion to the more potent 2-chain forms, and that hGH-B may represent a pituitary storage form serving as a prohormone. In order to test this hypothesis and to gain insight into the chemical nature of secreted hGH, we studied the synthesis and secretion of hGH by human pituitary glands in organ culture. One normal pituitary and 5 pituitaries from patients with pituitary disease (acromegaly, prolactinoma, Cushing's disease, and chromophobe adenoma) were studied. Biosynthetically labeled and unlabeled hGH secreted into the culture media was examined by polyacrylamide gel electrophoresis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and isoelectric focusing, as well as by immunochemical criteria. In all cases the predominant form secreted was hGH-B (22,000 mol wt intact chain). Cleaved two-chain forms of hGH and 20K-hGH were below the detection threshold (i.e. less than 5‰ of all hGH). We conclude that, in vitro, 1) the pituitary secretes primarily the single-chain 22,000 mol wt form, 2) proteolytically activated 2-chain hGH is not a major secretory product, and 3) hGH secreted by acromegalic pituitary tissue is qualitatively indistinguishable from normal hGH. (J Clin Endocrinol Metab55: 611, 1982)