Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in normal human endometrium throughout the menstrual cycle

Abstract

Inhibins are dimeric glycoproteins composed of an alpha (alpha) subunit and one of two possible beta (beta-) subunits (betaA or betaB). The aims of this study were to assess the frequency and tissue distribution patterns of the inhibin subunits in normal human endometrium. Samples from human endometrium from proliferative phase (PP; n=32), early secretory phase (ES; n=10) and late secretory phase (LS; n=12) were obtained. Immunohistochemistry, immunofluorescence and a statistical analysis were performed. All three inhibin subunits were expressed by normal endometrium by immunohistochemistry and immunofluorescence. Inhibin-alpha was primarily detected in glandular epithelial cells, while inhibin-beta subunits were additionally localised in stromal tissue. Inhibin-alpha staining reaction increased significantly between PP and ES (P<0.05), PP and LS (P<0.01), and ES and LS (P<0.02). Inhibin-betaA and -betaB were significant higher in LS than PP (P<0.05) and LS than ES (P<0.05). All three inhibin subunits were expressed by human endometrium varying across the menstrual cycle. This suggests substantial functions in human implantation of inhibin-alpha subunit, while stromal expression of the beta subunits could be important in the paracrine signalling for adequate endometrial maturation. The distinct expression in human endometrial tissue suggests a synthesis of inhibins into the lumen and a predominant secretion of activins into the stroma.

Inhibin-α subunit expression in uterine endometrioid adenocarcinomas and endometrial cancer cell lines: a potential prognostic factor

“…Although initially characterized as endocrine and paracrine hormonal regulators of the hypothalamic-pituitary-gonadal axis (18), it is now evident that inhibins and activins are expressed in a wide range of tissues including normal human endometrium (24), cultured human endometrial cells (22,56,57), hyperplastic and malignant human endometrial tissue (26,58,59). Recently, the differential immunohistochemical expression of the inhibin-·, -ßA and -ßB subunits was demonstrated in a cohort group of 302 endometrial cancer patients (23).…”

“…Immunohistochemistry was performed using a combination of pressure cooker heating and the standard streptavidin-biotin-peroxidase complex by using the mouse-IgG-Vectastain Elite ABC kit (Vector Laboratories, Burlingame, CA, USA) as previously described (23,24). The mouse monoclonal antibody used for the experiments was the inhibin-·, clone R1, monoclonal mouse IgG2a, diluted in PBS 1:50 as previously described (23)(24)(25).…”

“…Additionally, they have also been detected in endocrine tumors (19), including ovarian (19)(20)(21), endometrial (22)(23)(24)(25)(26) and breast cancer tissue (27,28). Moreover, their differential expression has suggested an important role in malignant cell transformation (19,22,23,25).…”

Inhibin-α subunit in normal and malignant human cervical tissue and cervical cancer cell lines

“…Immunohistochemistry was performed using a combination of pressure cooker heating and the standard streptavidin-biotin-peroxidase complex by using the mouse-IgG Vectastain Elite ABC kit (Vector Laboratories, Burlingame, CA, USA) as previously described (16,(25)(26)(27) with slightly modi fications.…”

“…Negative controls were performed by replacing the primary antibody with normal rabbit IgG as isotype control in the same dilution compared to the primary antibody, respectively. Immunohistochemical staining was performed using an appropriate positive control comprising ovaries containing follicular cysts (16,26,27). Positive cells showed a brownish color and negative controls as well as unstained cells were blue.…”