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Molecular Endocrinology Vol. 4, No. 2 356-362
doi:10.1210/mend-4-2-356
Copyright © 1990 by the Endocrine Society.
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Inhibition of Somatotroph Growth and Growth Hormone Biosynthesis by Activin in Vitro

Nils Billestrup, Consuelo González-Manchón*, Ellen Potter and Wylie Vale{dagger}

Clayton Foundation Laboratories for Peptide Biology, The Salk Institute La Jolla, California 92037
Department of Pharmacology, M-036, University of California-San Diego La Jolla, California 92093

Address requests for reprints to: Dr. Nils Billestrup, Hagedorn Research Laboratory, Niels Steensensvej 6, DK-2820 Gentofte, Denmark.

Abstract

Activin-A, a homodimeric protein composed of two inhibin βA-subunits, was first isolated from gonadal fluids based upon its ability to stimulate FSH secretion and biosynthesis, but was also observed to suppress GH secretion. The present report describes the effects of activin on the biosynthesis of GH and the proliferation of pituitary somatotrophs. In pituitary cells cultured in the presence of 0.7 nM activin for 3 days, GH secretion was decreased by 50% compared to the control value. Inhibition of GH biosynthesis, measured by quantitative immunoprecipitation of [35S]methionine-labeled cells, could be observed after 24 h of activin treatment, and maximal (70%) inhibition of GH biosynthesis was observed after 3 days. Activin inhibited basal as well as GH-releasing factor (GRF)-, glucocorticoid-, and thyroid hormone-stimulated GH biosynthesis. Inhibin, which is known to reverse the effect of activin on FSH secretion, did not reverse the effect of activin on GH biosynthesis. Treatment of somatotrophs with activin for 3 days completely inhibited the growthpromoting effect of GRF on somatotrophs. However, no effect of activin on GRF-stimulated expression of the c-fos protooncogene was observed. These data demonstrate that activin, in addition to its stimulatory effect on FSH secretion, is able to inhibit both expression of GH and growth of somatotropic cells.

FOOTNOTES

This work was supported by NIH Grants DK-26741 and HD-13527 and was conducted in part by the Clayton Foundation for Research, California Division, and the Keck Foundation.

* Supported by the Consejo Superior de Investigaciones Cientificas (Madrid, Spain).

{dagger} Senior Clayton Foundation Investigator.

Received for publication September 13, 1989. Revision received November 6, 1989. Accepted for publication November 6, 1989.




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