Presence of corticotropin-releasing factor-like immunoreactivity in human tumors.

Corticotropin-releasing factor (CRF)-like immunoreactivity was measured by radioimmunoassay in human organs and tumors associated with and without ectopic adrenocorticotropic hormone (ACTH) syndrome. It was found to be distributed widely in the stomach, pancreas, adrenal gland, and various tumors (e.g., medullary thyroid carcinoma, small cell carcinoma of the lung, pheochromocytoma, and adenocarcinoma of the gastrointestinal tract and pancreas) in a concentration less than one tenth of that of the hypothalamus. Dilution curves of CRF-like immunoreactivity in tissue extracts paralleled that of synthetic rat (human) CRF. Sephadex G-50 gel filtration showed that a major CRF-like immunoreactivity in tissue extracts coeluted with synthetic rat (human) CRF. Results suggest that a material(s) closely related immunologically to CRF is present widely in normal and tumor tissues outside of the central nervous system.

Gamma-melanotrophin-like immunoreactivities in human pituitaries, ACTH-producing pituitary adenomas, and ectopic ACTH-producing tumours: evidence for an abnormality in glycosylation in ectopic ACTH-producing tumours.

Using gel exclusion chromatography on Bio-Gel P-60, gamma-melanotropin-like immunoreactivity (gamma-MSH-LI) in three human pituitary glands, two ACTH-producing pituitary adenomas, and three ectopic ACTH-producing tumours (two medullary thyroid carcinomas and one thymoma) was divided into one or two molecular weight classes. The largest component eluted near the position of mouse 16K fragment and was designated big gamma-MSH-LI. This big gamma-MSH-LI was present in all samples. The second one, designated intermediate gamma-MSH-LI, eluted between the position of mouse 16K fragment and human ACTH, and was demonstrated only in two ectopic ACTH-producing tumours. No gamma-MSH-LI emerged at the elution position of synthetic gamma 3-MSH. Affinity chromatography on concanavalin A-agarose revealed that a significant fraction (52-68%) of gamma-MSH-LI from human pituitary glands, ACTH-producing pituitary adenomas, and one ectopic ACTH-producing tumour bound to the column and was eluted with alpha-methyl-D-mannopyranoside. In two ectopic ACTH-producing tumours which contained big and intermediate gamma-MSH-LI, a relatively small fraction (27-35%) of gamma-MSH-LI bound to the column and was similarly eluted. These observations suggest that human gamma-MSH-LI is glycosylated and that there is an abnormality in the glycosylation of gamma-MSH-LI in some ectopic ACTH-producing tumours.

ACTH LPH and related peptides in the ectopic ACTH syndrome.

Adrenocorticotrophin, lipotrophin and the related peptides alpha-MSH, CLIP, beta-endorphin and met-enkephalin have been measured, and characterized chromatographically in tumour extracts from seven patients with the ectopic ACTH syndrome. Four of the seven tumours contained the complete family of peptides, although the proportion of one to another varied between tumours. In addition, large molecule weight forms of ACTH and met-enkephalin were seen. The potential clinical importance of these observations is discussed.

High molecular weight forms of immunoreactive ACTH in a human pituitary and ectopic ACTH-producing tumors.

High molecular weight forms of immunoreactive ACTH (IR-ACTH) were studied in a human pituitary gland and 4 ectopic ACTH-producing tumors in man. Both the pituitary and tumor extracts contained "big" IR-ACTH, which eluted near the void volume, and a small amount of "intermediate" IR-ACTH components, which eluted between the void volume and 125I-alpha h1-39 ACTH, in addition to "little" ACTH which coeluted with 125I-alpha h1-39ACTH by Sephadex G-100 gel filtration. A significant amount of the "big" IR-ACTH applied bound to the concanavalin A-agarose column and was eluted with 0.2 M alpha-methyl-D-mannopyranoside, indicating the glycoprotein content of "big" IR-ACTH fractions. When the "big" and "intermediate" fractions were further analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, they were resolved into 4 molecular forms of IR-ACTH with apparent molecular weight of 37,000, 24,000 , 18,000 and 4,500, respectively. These results indicate that 3 high molecular forms of IR-ACTH are present in the human pituitary and the ectopic ACTH-producing tumors.