Demonstration of Activin in Normal Pituitary and in Various Human Pituitary Adenomas by Immunohistochemistry.

Abstract

Abstract. Inhibins and activins have been known to modify the secretion of various pituitary hormones. To study whether inhibins and activins are present in human pituitary tissues, immunohistochemical studies with antisera to activin A and inhibin a subunit were performed on 9 human pituitary adenoma tissue specimens and one sample of normal pituitary tissue adjacent to one adenoma. Activin immunoreactivities were demonstrated in the cytoplasms of one GH and one PRL and two nonfunctioning adenomas and one normal pituitary tissue, but they were negative in one PRL, one ACTH, one FSH and two non-functioning adenomas. Thus, the presence and absence of activin in the same type of adenoma in regard to hormone production, suggested that the difference in immunostaining simply reflected the difference in the activin concentration.In contrast to this, inhibin a subunit immunoreactivity was not found in any of the tissues studied. These data suggested a local synthesis of activin in the normal pituitary as well as various kinds of pituitary adenoma tissues and its local role in the human pituitary gland.

Immunohistochemical localization of α- and βA-subunits of inhibin/activin in human normal endocrine cells and related tumors of the digestive system

“…Moreover, inhibin and activin have been demonstrated immunohistochemically in various types of pituitary adenomas [4,30], but, as far as we know, there are no reports regarding the identification of these peptides in tumours of the gastro-entero-pancreatic endocrine system.…”

ALK7 expression in prolactinoma is associated with reduced prolactin and increased proliferation

“…Indeed, TGF-β superfamily members, notably Activin and BMP, have been reported to exert regulatory functions in embryonic and adult pituitary gland (Bilezikjian et al 2006) but have also been implicated in the pathogenesis of human pituitary adenomas , Uccella et al 2000, Takeda et al 2003). Yet Activin expression is found in all pituitary tumours (Alexander et al 1995, Demura et al 1996, little was known, until now, about the impact on their signalling in prolactinomas and the underlying mechanism of their action through ALK4 and ALK7 receptors.…”

“…Reported detection of ActivinA and ActivinB in prolactinomas (Alexander et al 1995, Demura et al 1996 led us to investigate the expression of their cognate receptor ALK7 in prolactinomas. To do so, we took advantage of the well-established SMtTW3 prolactinoma model based on the allograft of a spontaneous prolactin transplantable tumour from Wistar/Furth Rat (Trouillas et al 1990).…”

“…Contribution of other TGFβ/BMP ligands such as Activin and Inhibin, originally identified and characterized as FSH-releasing and -inhibiting factors (Bilezikjian et al 2006) is well established in gonadotroph tumours but less studied in prolactinomas (Takeda et al 2003). This observation is rather surprising as Activin-ligands expression was confirmed by histological approaches in all types of pituitary adenomas including prolactinomas (Alexander et al 1995, Demura et al 1996. Previous in vitro work reports that Activins inhibitory effect on GH4 cell proliferation is less effective than the one mediated by TGFβ, while its capacity to enhance adhesion and inhibiting prolactin production is similar (Ramsdell 1991, Lebrun 2009).…”

From prolactin cell to prolactinoma: implications of ontogenic mechanisms in diagnosis and management

“…EGF potently stimulates PRL expression (Murdoch et al 1982) and overexpression of EGF and EGF-R was found in seven lactotroph adenomas (LeRiche et al 1996). Activin, a TGF-β-related cytokine and the type I and type II activin TGF-β receptors have been shown to be abundant in human prolactinomas (Alexander et al 1995, 1996, Demura et al 1996. TGF-α colocalizes with PRL in lactotrophs in the normal pituitary and in PRL-secreting adenomas (Kobrin et al 1987).…”