Enhanced ERbeta immunoexpression and apoptosis in the germ cells of cimetidine-treated rats

Sasso-Cerri, Estela

doi:10.1186/1477-7827-7-127

Cited by 29 publications

(24 citation statements)

References 48 publications

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“…Our current finding of the ERb absence in germ cells differs from the reports of other authors who found ERb-immunopositivity in gonocytes, spermatogonia, pachytene spermatocytes, round and elongated spermatids [47,48]. These discrepancies could be explained by the data of Carreau and Hess [1] who described testicular ERb-expression to be dependent on species, subjects within one species as well as preservation techniques and antibodies used for immunohistochemistry.…”

Section: Discussioncontrasting

confidence: 57%

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

Pilutin

Misiakiewicz-Has²,

Kolasa³

et al. 2014

Folia Histochem Cytobiol.

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Abstract:The function of testis is under hormonal control and any disturbance of hormonal homeostasis can lead to morphological and physiological changes. Therefore the aim of the study was to investigate the expression of androgen and estrogen receptors (AR, ERs), vanilloid receptor (TRPV1), cytochrome P450 aromatase (P450arom), as well as apoptosis of cells in testis of adult rats chronically treated with letrozole (LT), a non-steroidal aromatase inhibitor, for 6 months. The testicular tissues were fixed in Bouin's fixative and embedded in paraffin. Immunohistochemistry with monoclonal antibodies (abs) against AR, ERa, P450arom, and polyclonal abs against ERb, TRPV1, caspase-3 was applied. Long-lasting estradiol deficiency, as an effect of LT treatment, produced changes in the morphology of testis and altered the expression of the studied receptors in cells of the seminiferous tubules and rate of cell apoptosis. The immunostaining for AR was found in the nuclei of Sertoli cells and the cytoplasm of spermatogonia and spermatocytes in III-IV stages of the seminiferous epithelium cycle. The intensity of staining for P450arom was lower in the testis of LT-treated rats as compared to control animals. The immunofluorescence of ERa and ERb was observed exclusively in the nuclei of Leydig cells of LT-treated rats. There were no changes in localization of TRPV1, however, the intensity of reaction was stronger in germ cells of the seminiferous epithelium after LT treatment. The apoptosis in both groups of animals was observed within the population of spermatocytes and spermatids in II and III stages of the seminiferous epithelium cycle. In testis of LT-treated rats the immunoexpression of caspase-3 was additionally found in the germ cells in I and IV stages, and Sertoli, myoid and Leydig cells. In conclusion, our results underline the important role of letrozole treatment in the proper function of male reproductive system, and additionally demonstrate that hormonal imbalance can produce the morphological abnormalities in testis.

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Section: Discussioncontrasting

confidence: 57%

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

Pilutin

Misiakiewicz-Has²,

Kolasa³

et al. 2014

Folia Histochem Cytobiol.

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“…In this study, ER ␤ immunolabelling was observed in different germ cell types, including PGCs, and also in Leydig cells in animals collected during summer. The presence of ER ␤ in the male reproductive system has been documented in Leydig cells [Carreau and Hess, 2010] as well as in different cells of germinal lineage, including the spermatogonia of different mammal species [van Pelt et al, 1999;Sasso-Cerri, 2009;Carreau and Hess, 2010] and amphibians [Arenas et al, 2001]. The presence of ERs in a determined cell indicates a direct action of estrogen in this cell [Berensztein et al, 2006].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated the important role of estrogen on the spermatogenic process including germ cell proliferation, differentiation, the final maturation of spermatids as well as germ cell survival and apoptosis [Sasso-Cerri, 2009;Carreau and Hess, 2010]. The irreversible conversion of androgens into estrogens is catalyzed by the cytochrome P450 aromatase enzyme, a product of a unique gene called Cyp19 [Simpson et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

“…In this seasonal period, PGCs showed weak or absent testosterone immunoexpression [Sasso-Cerri et al, 2005]. Considering that testosterone is converted into estrogen by aromatase and that the importance of estrogen during spermatogenesis has been confirmed in many vertebrates [Callard, 1992;Polzonetti-Magni et al, 1998;van Pelt et al, 1999;Arenas et al, 2001;Sasso-Cerri, 2009], it has been suggested that the testosterone present in the winter PGCs might be converted into estrogen between spring and summer [Sasso- Cerri et al, 2005]. It is known that estrogen action is via two high-affinity estrogen receptors (ERs): ER ␣ and ER ␤ [Carreau and Hess, 2010] and that the presence of ERs in a determined cell indicates a direct action of estrogen in this cell [Berensztein et al, 2006].…”

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confidence: 99%

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Primordial Germ Cells (Spermatogonial Stem Cells) of Bullfrogs Express Sex Hormone-Binding Globulin and Steroid Receptors during Seasonal Spermatogenesis

Caneguim

Beltrame

Luz

et al. 2012

Cells Tissues Organs

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In vertebrate species, testosterone seems to inhibit spermatogonial differentiation and proliferation. However, this androgen can also be converted, via aromatase, into estrogen which stimulates spermatogonial differentiation and mitotic activity. During seasonal spermatogenesis of adult bullfrogs Lithobates catesbeianus, primordial germ cells (PGCs) show enhanced testosterone cytoplasm immunoexpression in winter; however, in summer, weak or no testosterone immunolabelling was observed. The aim of this study was to confirm if PGCs express stem cell markers – alkaline phosphatase (AP) activity and GFRα1 (glial-cell-line-derived neurotrophic factor) – and verify whether testosterone is maintained in these cells by androgen receptors (ARs) and/or sex hormone-binding globulin (SHBG) in winter. Furthermore, regarding the possibility that testosterone is converted into estrogen by PGCs in summer, the immunoexpression of estrogen receptor (ER)β was investigated. Bullfrog testes were collected in winter and in summer and were embedded in glycol methacrylate for morphological analyses or in paraffin for the histochemical detection of AP activity. GFRα1, AR, SHBG and ERβ expression were detected by Western blot and immunohistochemical analyses. The expression of AP activity and GFRα1 in the PGCs suggest that these cells are spermatogonial stem cells. In winter, the cytoplasmic immunoexpression of ARs and SHBG in the PGCs indicates that testosterone is maintained by these proteins in these cells. The cytoplasmic immunoexpression of ERβ, in summer, also points to an ER-mediated action of estrogen in PGCs. The results indicate a participation of testosterone and estrogen in the control of the primordial spermatogonia during the seasonal spermatogenesis of L. catesbeianus.

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“…A later in vivo system study conducted by Sasso-Cerri and Miraglia [48] found that cimetidine may lead to detachment and apoptosis of Sertoli cells and thus affect negatively sperm quality. In 2009, Sasso-Cerri confirmed these findings and showed that cimetidine at the same concentration enhances oestrogen receptor beta, a nuclear receptor activated by the sex hormone oestrogen, immunoexpression and apoptosis in germ cells of adult male rats [49]. H2RA, histamine-2 receptor antagonist.…”

Section: Effect Of Cimetidinementioning

confidence: 86%

Histamine‐2 Receptor Antagonists and Semen Quality

Banihani

2015

Basic Clin Pharma Tox

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Histamine-2 receptor antagonists are a class of drugs used to treat the acid-related gastrointestinal diseases such as ulcer and gastro-oesophageal reflux disease. Although such drugs, especially ranitidine and famotidine, are still widely used, their effects on semen quality, and hence on male infertility, is still unclear. This MiniReview systematically addresses and summarizes the effect of histamine-2 receptor antagonists (cimetidine, ranitidine, nizatidine and famotidine) on semen quality, particularly, on sperm function. Cimetidine appears to have adverse effects on semen quality. While the effects of ranitidine and nizatidine on semen quality are still controversial, famotidine does not appear to change semen quality. Therefore, additional studies will be required to clarify whether histamine-2 receptor-independent effects of these drugs play a role in semen quality as well as further clinical studies including direct comparison of the histamine-2 receptor antagonists.The histamine-2 (H2) receptors are widely expressed and can be found in gastric mucosal cells, heart, central nervous system, immune cells, smooth muscles of the airway, vasculature and uterus [1]. They are positively coupled to adenylate cyclase via Gs alpha subunit [2,3]. The activation of histamine-2 receptors by histamine alters the activity of Gs and therefore enhances the intracellular cyclic AMP (cAMP) production [3]. cAMP activates protein kinase A, which phosphorylates the cytoskeletal proteins, leading to the transport of the H + /K + ATPase (proton pump) from the cytoplasm to the plasma membrane of parietal cells [3,4]. H2 receptor activation stimulates hydrochloric acid secretion from the acidsecreting parietal cells of the gastric mucosa, leads to smooth muscle relaxation in the vasculature and airways, increases cardiac rate and contractility, and mediates some of the immunomodulatory effects of histamine [1]. Histamine-2 receptor antagonists (H2RAs), also called H 2 -blockers (e.g. cimetidine, ranitidine, nizatidine and famotidine), are the medications used to reduce the amount of hydrochloric acid produced by the stomach [5][6][7]. Mechanistically, these drugs are competitive antagonists of histamine-2 receptors [6,7]. In view of that, H2RAs are used to treat the acid-related gastrointestinal diseases such as gastrooesophageal reflux disease [8,9], dyspepsia [10-12], Zollinger-Ellison syndrome [13,14] and ulcer [15][16][17].Various studies have shown that proton pump inhibitors (e.g. omeprazole, lansoprazole, esomeprazole), another class of acid reducers with long-lasting reduction of gastric acid production [18,19], are more effective than H2RAs in treating acid-related gastrointestinal diseases such as gastrooesophageal reflux disease [20][21][22][23], ulcer [21,24], dyspepsia [25] and Zollinger-Ellison syndrome [26]; however, H2RAs are still widely used in the treatment of acid-related gastrointestinal diseases. One reason for this is that proton pump inhibitors therapy is more expensive and less cost-effective, ...

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Enhanced ERbeta immunoexpression and apoptosis in the germ cells of cimetidine-treated rats

Cited by 29 publications

References 48 publications

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

The immunoexpression of androgen receptor, estrogen receptors alpha and beta, vanilloid type 1 receptor and cytochrome p450 aromatase in rats testis chronically treated with letrozole, an aromatase inhibitor

Primordial Germ Cells (Spermatogonial Stem Cells) of Bullfrogs Express Sex Hormone-Binding Globulin and Steroid Receptors during Seasonal Spermatogenesis

Histamine‐2 Receptor Antagonists and Semen Quality

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