AJP - Endocrinology and Metabolism, Vol 244, Issue 4 346-E353, Copyright © 1983 by American Physiological Society
Biological activity of a growth hormone-releasing factor secreted by a human tumor
M. J. Cronin, A. D. Rogol, R. M. MacLeod, D. A. Keefer, I. S. Login, J. L. Borges and M. O. Thorner
A substance released by a pancreatic islet cell tumor induced signs and
symptoms of acromegaly in a young woman. The culture medium in which the
tumor was placed after resection was added to rat anterior pituitary cells
and incubated in vitro. Both newly synthesized and total rat growth hormone
(GH) release as well as cellular cyclic AMP accumulation were stimulated in
a dose-dependent manner by the tumor medium. Coincubation with somatostatin
blocked these effects. The increase of cyclic AMP preceded the enhanced GH
release, indicating that cyclic AMP may be a second messenger for the tumor
factor(s). Neither prolactin nor luteinizing hormone secretion was affected
by the tumor medium. When measured by a perfused cell column apparatus,
there was a rapid and dramatic release of GH by the dispersed rat pituitary
cells during a 2.5-, 10-, and 40-min pulse of tumor medium; both the onset
and termination of the GH response reached maximal or control values,
respectively, within 5 min. Pretreatment of the tumor medium with pepsin
markedly attenuated the tumor medium activity, indicating the peptide
nature of the factor(s). Finally, ultrastructural analysis indicated that
the somatotrophs were degranulated by the tumor medium, whereas there was
no similar effect apparent on the mammotrophs. Whether this tumor
polypeptide is identical to native hypothalamic GH-releasing hormone
remains to be proved.
