Inhibition of somatotroph growth and growth hormone biosynthesis by activin in vitro

Nils Billestrup, C González-Manchón, E Potter, W Vale

    99 Citations (Scopus)

    Abstract

    Activin-A, a homodimeric protein composed of two inhibin beta A-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 growth-promoting 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.

    Original languageEnglish
    JournalMolecular endocrinology (Baltimore, Md.)
    Volume4
    Issue number2
    Pages (from-to)356-62
    Number of pages7
    ISSN0888-8809
    DOIs
    Publication statusPublished - Feb 1990

    Keywords

    • Activins
    • Animals
    • Cell Division
    • Cells, Cultured
    • Gene Expression
    • Growth Hormone
    • Inhibins
    • Male
    • Pituitary Gland
    • Precipitin Tests
    • Proto-Oncogene Proteins
    • Proto-Oncogene Proteins c-fos
    • Rats
    • Rats, Inbred Strains

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