Pituitary lactotrope expresses transforming growth factor β (TGFβ) type II receptor mRNA and protein and contains 125I-TGFβ1 binding sites

Abstract

Transforming growth factor beta 1 (TGF beta 1) has recently been shown to be produced in the prolactin (PRL)-secreting lactotropes of the pituitary gland. TGF beta 1 inhibits lactotropic secretion and proliferation, and the production of TGF beta 1 in lactotropes is reduced during lactotropic growth following estrogen treatment in ovariectomized rats. In many estrogen-responsive tissues, TGF beta 1 has been shown to exert its effect by binding to TGF beta 1 type II receptors (T beta R II) at the cell surface. In this study, we sought to ascertain whether T beta R II is involved in TGF beta 1 action on lactotropes by determining the changes of T beta R II mRNA and protein levels and specific 125I-TGF beta 1 binding sites on the lactotropes during estrogen-induced proliferation of lactotropes in Fischer 344 rats. Double immunohistochemical procedures were employed to identify immunoreactive T beta R II in PRL-reactive cells. The majority of T beta R II-reactive cells in the anterior pituitary were observed to be lactotropes. Dual immunohistochemistry and in situ hybridization procedures also indicated that lactotropes were the major cell types containing T beta R II mRNA hybrids. Both the levels of immunoreactive T beta R II protein and in situ T beta R II mRNA hybrids in the pituitary were significantly decreased in ovariectomized rats after 15 days of estrogen treatment. Determination of 125I-TGF beta 1 binding sites in lactotropes by double immunohistochemistry and receptor autoradiography also revealed specific binding sites of 125I-TGF beta 1 in lactotropes in the anterior pituitary. 125I-TGF beta 1 binding in the anterior pituitary was also reduced following estrogen treatment in ovariectomized rats. These data suggest that down-regulation of T beta R II may be an important mechanism of estrogen action on lactotropic cell growth and PRL secretion, and further support the notion that TGF beta 1 controls lactotropic function by autocrine/paracrine mechanisms.

Expression of differentially expressed nucleolar transforming growth factor‐β1 target (DENTT) in adult mouse tissues

“…The pituitary gland is a site where TGF-␤ acts locally to control cell growth and function and exerts growth-inhibiting and differentiating influences as it does on many other tissues (Ramsdell, 1991;Sarkar et al, 1992). Within the pituitary gland, lactotropes of the anterior lobe of the pituitary and melanotropes of the intermediate pituitary gland have been shown to produce TGF-␤1 and TGF-␤3 (Sarkar et al, 1992(Sarkar et al, , 1998Burns and Sarkar, 1993;De et al, 1995;Pastorcic et al, 1995). However, TGF-␤1 and TGF-␤3 are thought to have contrasting and opposite actions on lactotropic proliferation in the pituitary, with TGF-␤1 inhibiting pituitary cell growth, whereas TGF-␤3 increases lactotropic cell growth (Hentges et al, 2000).…”

Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals

“…The inhibitory response to TGF-β1 is reduced in anterior pituitary cell lines, including the prolactin-secreting PR1 cell line and the GH and prolactin-secreting GH3 cell line. Both of these cell lines show low levels of TGF-β1 and its type II receptor (TβR-II) mRNA [67]. Lactotropes exposed to estrogen express reduced levels of TβR-II and TGF-β1 [68,69].…”

“…One explanation for TGF-β3's inability to be self-inhibitory is that the TGF-β receptors on lactotropes have a low affinity for TGF-β3 [76]. Another possibility is that estrogen suppresses TGF-β that prevents the effect of TGF-β on lactotropes [67]. It has been shown that TGF-β1 inhibits lactotropic cell proliferation and that this response is mediated largely via the TGF-β type II receptors [67].…”

“…Another possibility is that estrogen suppresses TGF-β that prevents the effect of TGF-β on lactotropes [67]. It has been shown that TGF-β1 inhibits lactotropic cell proliferation and that this response is mediated largely via the TGF-β type II receptors [67]. The TGF-β type I receptor in the pituitary has been implicated to be more involved in transcription responses evoked by TGF-β [76].…”

“…A rat pituitary derived PR1 cell line, which has reduced levels of type II receptors [68,76], displays very little or no growth-inhibitory response to TGF-β1 [67]. However, in the presence of TGF-β type I receptors and very low expression of TGF-β type II receptors, TGF-β1 inhibits PRL secretion in PR1 cells [76].…”