Inhibition of Somatotroph Growth and Growth Hormone Biosynthesis by Activinin Vitro

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.

Expression of Inhibin .ALPHA., and .BETA.A Subunit and Activin Type II Receptor mRNAs in Various Human Pituitary Adenomas.

“…THE ROLE of inhibin and activin in the endocrineautocrine-paracrine regulation of pituitary hormone secretion has been a matter of recent interest [1][2][3][4][5][6][7][8][9]. The diverse effects of inhibin and activin on FSH secretion [1] as well as the inhibitory effect of activin on somatotrophs [2,3] and corticotrophs [4,5] indicate that different populations of pituitary cells are the targets of these peptides.…”

“…The diverse effects of inhibin and activin on FSH secretion [1] as well as the inhibitory effect of activin on somatotrophs [2,3] and corticotrophs [4,5] indicate that different populations of pituitary cells are the targets of these peptides. Expression of inhibin a and /3 subunit mRNAs in the rat pituitary cells showed the ability of pituitary cells to synthesize inhibin a and /3 subunits [6,7].…”

Involvement of Distinct Signaling Pathways in Activin-Induced Increases in FSH Secretion and Enlargement of FSH Cell Population in the Rat Pituitary.

“…With respect to pituitary cells, activin suppresses, but does not stimulate, proliferation of the GH4C1 rat pituitary cell line [23] and GRF-stimulated proliferation of purified somatotropes [24] . We were unable to detect an effect of activin-A on proliferation of the pituitary folliculo-stellate-like cell line, TtT/GF [25] (unpublished observation by Tetsuro Katayama).…”

Effect of Activin A and Follistatin on the Release of Pituitary Hormones in the Bullfrog Rana catesbeiana

“…In mammals, there are some reports on the effects of activin on the release of GH and PRL. Incubation of rat anterior pituitary cells with activin A results in a reduction in basal GH secretion (Billestrup et al, 1990). Also, activin A suppresses GHreleasing hormone-induced GH release (Billestrup et al, 1990;Kitaoka et al, 1988).…”

“…Incubation of rat anterior pituitary cells with activin A results in a reduction in basal GH secretion (Billestrup et al, 1990). Also, activin A suppresses GHreleasing hormone-induced GH release (Billestrup et al, 1990;Kitaoka et al, 1988). On the other hand, activin A has no effect on basal PRL secretion but restrains TRH-induced PRL release (Kitaoka et al, 1988).…”