Expression of Inhibin/Activin Subunits Alpha (-α), BetaA (-βA), and BetaB (-βB) in Placental Tissue of Normal, Preeclamptic, and HELLP Pregnancies

Abstract

During human pregnancy the placenta produces a variety of proteins for the establishment of the fetoplacental unit, including inhibins and activins. Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB). Aims of the present study were (a) the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) and (b) the assessment of a combined expression of inhibin-alpha- and both beta-subunits (betaA-and betaB-subunits) using double immunofluorescence technique. A significant lower expression of the inhibin-alpha subunit in preeclamptic and HELLP placental tissue compared to normal pregnancies was observed, while the inhibin-alpha immunostaining was significantly upregulated in syncytotrophoblast. Additionally, we demonstrated a significant down-regulation of inhibin-betaB subunit in extravillous trophoblast cells between normal and preeclamptic compared to HELLP placental tissue, while inhibin-betaA-subunit was significantly higher in preeclamptic syncytotrophoblast cells. A colocalization of inhibin-alpha and the beta-subunits could be demonstrated, suggesting a production and secretion of intact inhibin A and inhibin B. Therefore, inhibin A and activin A might be useful markers in preeclampsia. Valuable parameters in HELLP syndrome could be inhibin A, rather than inhibin B, and activin B. Furthermore, the lower betaB-subunit production in extravillous trophoblast cells demonstrates that this subunit might have an important role in the pathogenesis of HELLP syndrome. Additionally, the higher production of the betaA-subunit in syncytotrophoblast cells suggest a higher production of activin A rather than inhibin A in preeclampsia that might be utilized as a marker of placental function.

Expression of the inhibin/activin subunits (-α, -βA and -βB) in normal and carcinogenic endometrial tissue: Possible immunohistochemical differentiation markers

“…While inhibins/activins were initially characterized as endocrine and paracrine hormonal regulators of the hypothalamicpituitary-gonadal axis it is now evident that they are expressed in a wide range of tissues including breast cancer (18,19), the placenta (20)(21)(22), human endometria (5,7,13,16), cultured human endometrial cells (6,12,23), hyperplastic and malignant human endometrial tissue (7)(8)(9)(10)(11)13). We demonstrated a significantly higher inhibin-· expression in the secretory compared to the proliferative endometrial tissue, confirming previous immunohistochemical (6,16) and in vitro results (6,23).…”

Evidence of inhibin/activin subunit betaC and betaE synthesis in normal human endometrial tissue

“…The immunohistochemical procedures for inhibin α-, βA- and βB-subunits were evaluated in normal and malignant endometrial tissue [11-13,42,43], breast cancer tissue [44], and uterine cervical cancer [45] as well as normal and abnormal placenta [46,47]. The inhibin βC antibody was previously evaluated in normal and pathological placenta tissue [28,29], endometrial cell lines [30,31], endometrial cancer [32] and cervical tissue [33].…”

Inhibin/activin-betaE subunit in normal and malignant human cervical tissue and cervical cancer cell lines

“…), using a semi-quantitative score as previously described and used to asses the expression pattern of inhibin/activin subunits in endometrial and placental tissue (Mylonas et al 2004;Mylonas et al 2006b;Mylonas et al 2006c;Mylonas et al 2009b). The IRS score was calculated by multiplication of optical staining intensity (graded as 0 = no, 1 = weak, 2 = moderate and 3 = strong staining) and the percentage of positive stained cells (0 = no staining, 1 = \10% of the cells, 2 = 11-50% of the cells, 3 = 51-80% of the cells and 4 = [81% of the cells).…”

“…Inhibins and activins have been demonstrated in normal and neoplastic tissue (Risbridger et al 2001), including breast cancer (Mylonas et al 2005a;Reis et al 2004), ovarian cancer (Robertson et al 2007;Zheng et al 1998), normal and pathological placental tissue Mylonas et al 2006b;Mylonas et al 2006c;Mylonas et al 2007) as well as normal and pathological endometrial tissue (Mylonas et al 2004;Mylonas et al 2005b;Mylonas et al 2006a;Mylonas et al 2009b;Worbs et al 2007). These members of the TGFb-familiy have been implicated in several important functions including in stem cell biology (Beattie et al 2005), reproductive biology (de Kretser et al 2002), systemic inflammation (Phillips et al 2009), carcinogenesis (Risbridger et al 2004), tumour suppressor activity (Matzuk et al 1992) and apoptosis (Chen et al 2002).…”