Cimetidine‐induced androgenic failure causes cell death and changes in actin, EGF and V‐ATPase immunoexpression in rat submandibular glands. Issue 1 (13th March 2021)

• Record Type: Journal Article
• Authors: Manzato, Mariane Castro; de Santi, Fabiane; da Silva, André Acácio Souza; Beltrame, Flávia L.; Cerri, Paulo S.; Sasso‐Cerri, Estela
• Is Part Of: Journal of anatomy. Volume 239:Issue 1(2021)
• Page Start: 136
• Page End: 150
• Publication Date: 2021-03-13
• Subjects: antiandrogen -- apoptosis -- AR -- salivary glands -- testosterone; Anatomy -- Periodicals; 571.3
• DOI: 10.1111/joa.13408
• Languages: English
• ISSNs: 0021-8782

Abstract

Abstract: Submandibular gland (SMG) is responsive to androgens via androgen receptor (AR). We verified whether cimetidine induces androgenic dysfunction in SMG, and evaluated the structural integrity, cell death and immunoexpression of actin, EGF and V‐ATPase in androgen‐deficient SMG. Male rats received cimetidine (CMTG) and control animals (CG) received saline. Granular convoluted tubules (GCTs) diameter and number of acinar cell nuclei were evaluated. TUNEL and immunofluorescence reactions for detection of AR, testosterone, actin, EGF and V‐ATPase were quantitatively analysed. In CG, testosterone immunolabelling was detected in acinar and ductal cells cytoplasm. AR‐immunolabelled nuclei were observed in acinar cells whereas ductal cells showed AR‐immunostained cytoplasm, indicating a non‐genomic AR action. In CMTG, the weak testosterone and AR immunoexpression confirmed cimetidine‐induced androgenic failure. A high cell death index was correlated with decreased number of acinar cells, GCTs diameter and EGF immunoexpression under androgenic dysfunction. Actin immunofluorescence decreased in the SMG cells, but an increased and diffuse cytoplasmic V‐ATPase immunolabelling was observed in striated ducts, suggesting a disruption in the actin‐dependent V‐ATPase recycling due to androgenic failure. Our findings reinforce the androgenic role in the maintenance of SMG histophysiology, and point to a potential clinical use of cimetidine against androgen‐dependent glandular tumour cells. Abstract : Cimetidine causes androgenic failure in submandibular gland (SMG), culminating in reduced number of acinar cells, granular convoluted tubules (GCT) diameter and high index of cell death. The decreased EGF immunoexpression in GCT indicates that SMG cells viability depends on androgen‐mediated EGF. The reduced actin immunoexpression in SMG in contrast with an intense V‐ATPase immunolabelling in striated ducts suggests a disruption in the actin‐dependent V‐ATPase recycling due to androgenic failure.