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Effects of TGF‐β1 on Prolactin Synthesis and Secretion: an In‐Vitro Study
Author(s) -
Raquel Coya,
Clara V. Álvarez,
Pérez Franco,
Cristina Gianzo,
Carlos Diéguez
Publication year - 1999
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.1999.00336.x
Subject(s) - prolactin , medicine , endocrinology , prolactin cell , secretion , dopamine , anterior pituitary , hypothalamus , pituitary gland , forskolin , biology , chemistry , hormone , stimulation
The hypothalamus exerts a predominantly inhibitory influence on prolactin secretion through dopamine. In addition, the expression of anterior pituitary hormone‐gene products are regulated by intrapituitary growth factors. In particular, TGF‐ β 1 produced in the pituitary regulates lactotroph cell proliferation and prolactin gene‐expression. This study characterized the regulation of in‐vitro prolactin synthesis and secretion by TGF‐ β 1 using rat anterior pituitary cells in monolayer culture. Furthermore, we studied the interaction of TGF‐ β 1 with other signals involved in the neuroregulation of prolactin secretion, such as dopamine and TRH, as well as the importance of different signal transduction pathways in this response. TGF‐ β 1 inhibited prolactin secretion in a time‐ and concentration‐dependent manner, with half‐maximal inhibition occurring at the range of 15–30 pM. The inhibitory effect was observed after 4 h, being maximal after 4 days of exposure of the cells to the peptide. This inhibitory effect was mimicked by TGF‐ β 2 but not by inhibin, and was not influenced by oestrogens, being similar in male, normal female or oestradiol‐treated rats. Prolonged pretreatment of the cells with TGF‐ β 1(4 days) did not modify GH or TSH secretion nor dopamine‐induced inhibition of prolactin secretion, and blunted prolactin responses to TRH, Forskolin, But2‐cAMP and to the calcium ionophore A23187. The effect observed after long‐term treatment (24 h to 4 days) is essentially caused by a decrease in prolactin synthesis, since TGF‐ β 1 inhibited prolactin mRNA levels and de novo prolactin protein synthesis. However, in the short term (up to 12 h) TGF‐ β 1 inhibition of prolactin secretion was associated with an increase in intracellular prolactin content, dissecting a dual mechanism of action of TGF‐ β 1. The short‐term TGF‐ β 1 effect did not modify Erk‐2 phosphorylation, basal or TRH‐induced increase in intracellular calcium concentration, but blunted basal and forskolin stimulated cAMP levels. But2‐cAMP replacement did not revert the inhibition of prolactin secretion. However, pertussis toxin was able to recover a large percentage of TGF‐ β 1‐induced inhibition of prolactin secretion. This study indicates that TGF‐ β 1 plays a crucial role as a modulator of lactotroph function, inhibiting prolactin biosynthesis after long‐term treatment, as well as, after short‐term exposure prolactin secretion at the level of the secretory process, through a mechanism pertussis toxin sensitive but independent of Erk‐2 phosphorylation, calcium concentrations or intracellular cAMP.