Effects of recombinant human activin A on growth hormone secretion by human somatotrophinomas in vitro.
Activin A is a homodimer of inhibin beta A subunits, and was first isolated from gonadal fluids on the basis of its ability to stimulate FSH secretion by rat pituitary cells in vitro. The beta A subunits of activin and their mRNAs have been found in many cell types, in several species and at different stages of development, suggesting that activin A has a wide range of diverse biological roles. Apart from the modulation of gonadotroph function, in-vitro studies have demonstrated inhibitory effects of activin A on GH synthesis, GH secretion and possibly somatotroph proliferation. We have therefore investigated the potential role of activin A in the pathophysiological regulation of GH secretion by human somatotrophinoma cells using in-vitro techniques. Cell cultures were established by enzyme dispersion of adenoma tissue obtained from six patients with acromegaly, and treated for 72 h with 0.01-10 nmol recombinant human activin A/l followed by a 2-h stimulation test with 10 nmol GH-releasing factor (GRF)/l. Medium was collected at 24, 48 and 72 h, as well as after GRF treatment, and GH concentrations were measured by immunoradiometric assay. Basal GH secretion from the cells of two tumours was significantly stimulated 12-63% above control values during treatment with 0.01-10 nmol activin A/l, whereas the peptide had no effect on GH release from cells of the remainder of the tumours. GRF significantly stimulated GH release from the cells of two different adenomas, and pretreatment with 0.01-1 nmol activin A/1 partially but significantly blocked GRF-stimulated GH release from the cells of one of these.(ABSTRACT TRUNCATED AT 250 WORDS)
Daniels
M
M
Department of Medicine, Medical School, Newcastle upon Tyne, U.K.
Harris
P E
PE
James
R A
RA
Turner
S J
SJ
Dewar
J H
JH
Kendall-Taylor
P
P
D028341:Activins; D000368:Aged; D001971:Bromocriptine; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007265:Inhibins / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D015282:Octreotide; D010911:Pituitary Neoplasms / Q000097:blood / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013973:Thyrotropin-Releasing Hormone; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D006133:Growth Substances; D011994:Recombinant Proteins; D028341:Activins; D001971:Bromocriptine; D007265:Inhibins; D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D015282:Octreotide