Activin-A Modulates Growth Hormone Secretion from Cultures of Rat Anterior Pituitary Cells*
- 1 May 1990
- journal article
- research article
- Published by The Endocrine Society in Endocrinology
- Vol. 126 (5), 2369-2376
- https://doi.org/10.1210/endo-126-5-2369
Abstract
Activins, initially identified as FSH-releasing proteins, have now been shown to exert effects on other cell types of the anterior pituitary, including the somatotrophs. In the present study the inhibitory action of activin-A (.beta.A.beta.A) on GH secretion was characterized using primary cultures of rat anterior pituitary cells. Activin-A suppressed basal GH secretion for up to 72 h (the longest time tested). Immediately after the treatment period with activin-A, when the cells were thoroughly washed and further incubated with or without rat GH-releasing factor (rGRF), basal and stimulated GH secretion were partially inhibited as well. In parallel, activin-A pretreatment diminished rGRF-stimulated cAMP accumulation. The effects of activin-A were time- and concentration-dependent, with half-maximal inhibition occurring in the range of 20-30 pM activin-A. A minimum pretreatment time of 3 h was required for maximal effect, and when rGRF and activin-A were added simultaneously, no inhibition was evident. Secretory responses of activin-A-pretreated cells to rGRF were influenced by glucocorticoids. When cells were cultured in the presence of the synthetic glucocorticoid dexamethasone, pretreatment (72 h) with activin-A attenuated rGRF-stimulated GH secretion only during short (1-h), but not longer (3-h), exposure periods to the neuropeptide. In the absence of dexamethasone, rGRF-stimulated GH secretion was inhibited at all incubation times tested (up to 3 h). A 3-h exposure to the protein factor did not alter total (cellular plus secreted) immunoreactive GH levels, suggesting that the inhibition of secretion with the shorter treatment was not secondary to attenuated GH biosynthesis. However, longer (72-h) treatment with activin-A decreased total GH levels, indicating lower GH biosynthetic rates, as previously shown. Somatostatin is recognized as the primary negative modulator of GH secretion. Activin-A and SRIF inhibited GH secretion additively, suggesting distinct mechanisms of action for each. GH secretion in response to other secretagogues, such as 12-O-tetradecanoyl-phorbol-13-acetate, forskolin, cholera toxin, and 8-bromo-cAMP, was also suppressed after activin-A pretreatment. The presence of the RNA synthesis inhibitor actinomycin-D completely blocked the inhibitory effect of a 3-h activin-A pretreatment on subsequent rGRF-stimulated GH secretion. Pertussis toxin was only partially effective in preventing the inhibition by activin-A. The results of this study indicate that activin-A plays a crucial role as a modulator of somatotropic function, inhibiting GH secretion at the level of the secretory process and secondary to the inhibition of GH biosynthesis.This publication has 34 references indexed in Scilit:
- Purification and partial characterization of inhibin from porcine follicular fluidBiochemical and Biophysical Research Communications, 1985
- Isolation and partial characterization of a Mr 32,000 protein with inhibin activity from porcine follicular fluid.Proceedings of the National Academy of Sciences, 1985
- Isolation of porcine follicular fluid inhibin of 32K daltonsBiochemical and Biophysical Research Communications, 1985
- Phorbol esters affect pituitary growth hormone (GH) and prolactin release: The interaction with GH releasing factor, somatostatin and bromocriptineEuropean Journal of Pharmacology, 1985
- Isolation of inhibin from bovine follicular fluidBiochemical and Biophysical Research Communications, 1985
- Stimulation of Adenosine 3′,5′-Monophosphate Production by Growth Hormone-Releasing Factor and Its Inhibition by Somatostatin in Anterior Pituitary Cellsin Vitro*Endocrinology, 1983
- Glucocorticoids Inhibit Corticotropin-Releasing Factor-Induced Production of Adenosine 3′,5′-Monophosphate in Cultured Anterior Pituitary Cells*Endocrinology, 1983
- Glucocorticoid and thyroid hormones transcriptionally regulate growth hormone gene expression.Proceedings of the National Academy of Sciences, 1982
- Growth Hormone-Releasing Factor from a Human Pancreatic Tumor That Caused AcromegalyScience, 1982
- Secretion of an FSH-Inhibiting Factor by Cultured Sertoli CellsEndocrinology, 1976