Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Rat Efferent Duct Epithelium1

Leung, George Pak-Heng; Gong, Xiaowen; Cheung, King‐Ho; Cheng-Chew, S. B.; Wong, Patrick

doi:10.1093/biolreprod/64.5.1509

Cited by 20 publications

(12 citation statements)

References 33 publications

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“…We did not detect any changes on other aquaporins, although Shayu et al [50] described that ICI 182,780 downregulated Aqp4 in the mouse epididymis. The upregulation of Cftr (3 times) is also in accordance with previous findings that estrogen regulates secretion of Cl À through CFTR, and that Cftr gene transcription is estrogen dependent [24,52].…”

Section: Discussionsupporting

confidence: 91%

Effects of the Antiestrogen Fulvestrant (ICI 182,780) on Gene Expression of the Rat Efferent Ductules1

Yasuhara

Gomes

Siu

et al. 2008

Biology of Reproduction

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The efferent ductules express the highest amount of estrogen receptors ESR1 (ERalpha) and ESR2 (ERbeta) within the male reproductive tract. Treatment of rats with the antiestrogen fulvestrant (ICI 182,780) causes inhibition of fluid reabsorption in the efferent ductules, leading to seminiferous tubule atrophy and infertility. To provide a more comprehensive knowledge about the molecular targets for estrogen in the rat efferent ductules, we investigated the effects of ICI 182,780 treatment on gene expression using a microarray approach. Treatment with ICI 182,780 increased or reduced at least 2-fold the expression of 263 and 98 genes, respectively. Not surprisingly, several genes that encode ion channels and macromolecule transporters were affected. Interestingly, treatment with ICI 182,780 markedly altered the expression of genes related to extracellular matrix organization. Matrix metalloproteinase 7 (Mmp7), osteopontin (Spp1), and neuronal pentraxin 1 (Nptx1) were among the most altered genes in this category. Upregulation of Mmp7 and Spp1 and downregulation of Nptx1 were validated by Northern blot. Increase in Mmp7 expression was further confirmed by immunohistochemistry and probably accounted for the decrease in collagen content observed in the efferent ductules of ICI 182,780-treated animals. Downregulation of Nptx1 probably contributed to the extracellular matrix changes and decreased amyloid deposition in the efferent ductules of ICI 182,780-treated animals. Identification of new molecular targets for estrogen action may help elucidate the regulatory role of this hormone in the male reproductive tract.

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Section: Discussionsupporting

confidence: 91%

Effects of the Antiestrogen Fulvestrant (ICI 182,780) on Gene Expression of the Rat Efferent Ductules1

Yasuhara

Gomes

Siu

et al. 2008

Biology of Reproduction

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“…1). Further, cAMP has also been implicated in stimulating Cl Ϫ secretion in the efferent ducts [8], and this would drive fluid secretion into the duct. Support for this mechanism is indicated in Table 1, which shows that db-cAMP in the perfusate increased the concentration of Cl Ϫ in collectate.…”

Section: Discussionmentioning

confidence: 99%

“…It is interpreted that fluid reabsorption is mainly determined by sodium/hydrogen exchanger 3 (NHE3), an amiloride-sensitive Na ϩ -H ϩ antiport that accounts for 70% of the fluid reabsorbed by the proximal efferent ducts [5,6]. Secretion of fluid into the duct is probably determined by secretion of Cl Ϫ via the cystic fibrosis transmembrane conductance regulator, CFTR [7,8]. Na ϩ -K ϩ -ATPase is probably the main source of energy driving the solute transport, as its activity has been localized in the basolateral membranes of the ducts [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…Local, acute regulation of fluid reabsorption is determined by load, including the concentration of Na ϩ , and the rate of flow of fluid into the ducts [20]. However, although there is evidence, from studies of epithelium cultured in vitro, that cAMP can affect fluid reabsorption by acting on Cl Ϫ channels to stimulate fluid secretion into the ducts [8], the role of cyclic nucleotides in net fluid reabsorption has not been resolved. Consequently, we have examined the role of cyclic-nucleotides in net fluid reabsorption in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Signal Transduction in the Ductuli Efferentes Testis of the Rat: Inhibition of Fluid Reabsorption by Cyclic Adenosine 3′, 5′-Monophosphate1

Man

Clulow

Jones

2003

Biology of Reproduction

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It is important to identify the signal transduction pathway involved in the regulation of fluid reabsorption by the ductuli efferentes of the testis because they reabsorb most of the fluid leaving the testis and are essential for male fertility. Microperfusion studies of the ducts in vivo showed that 0.1 or 1.0 mM dibutyryl (db)-cGMP in the perfusate had no effect on fluid reabsorption, but 0.1 mM db-cAMP significantly reduced fluid reabsorption, 0.25 mM abolished reabsorption, and 0.5-1.0 mM caused secretion. The inhibitory effect of db-cAMP was reversible. Although the presence of db-cAMP in the perfusate did not affect the concentration of Na+ in the collectate, the concentrations of K(+) and Cl(-) increased, indicating that their transport is at least partly regulated by cAMP. Including the phosphodiesterase inhibitor pentoxifylline in the perfusate decreased fluid reabsorption by the ducts in a dose-dependent manner, and it also increased the concentration of cAMP (5.5-fold) in collectate. Pentoxifylline also increased the production of cAMP (4-fold) by ducts incubated in vitro. It is concluded that cAMP, but probably not cGMP, is an intracellular messenger regulating fluid reabsorption in the efferent ducts.

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“…Potential targets for regulation by relaxin include metalloproteinase 7 (MMP7, see Filonzi et al 2007) and the cystic fibrosis transmembrane regulator (CFTR), a multifunctional protein that is known to be a cAMPactivated Cl K channel, and which is important for fluid transport in the excurrent ducts of the male tract (Leung et al 2001, Ruz et al 2004, Pietrement et al 2008. MMP7 immunoreactivity was restricted to the supranuclear region of epithelial cells of the vas deferens (Fig.…”

Section: Localization Of Relaxin In the Testis And Effect Of Relaxin mentioning

confidence: 99%

Locally produced relaxin may affect testis and vas deferens function in rats

Cardoso¹,

Nascimento²,

Royer³

et al. 2010

Reproduction

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We have previously shown that the rat testis and vas deferens contain high levels of the relaxin receptor, RXFP1. The present study was undertaken to determine the expression of relaxin in these tissues, and the effect of exogenous relaxin on Sertoli cell proliferation and on the mRNA levels of some proteins that may contribute to epithelial secretion and tissue reorganization in the vas deferens. Relaxin mRNA levels in testis and vas deferens were much lower than in the prostate. Sertoli cells seem to be an important source of relaxin mRNA in testis. Relaxin immunoreactivity was detected in the seminiferous epithelium but not in the interstitial compartment. The relaxin precursor was expressed in the vas deferens, and relaxin immunoreactivity was detected in apical cells of the vas deferens. Castration, but not treatment with the anti-estrogen ICI 182,780, dramatically reduced relaxin mRNA levels in the prostate and vas deferens, and this effect was prevented by testosterone. Rxfp1 mRNA levels in the vas deferens and prostate were not affected by castration or treatment with ICI 182,780. Exogenous relaxin increased the incorporation of 3 H-thymidine in cultured Sertoli cells, and treatment of the vas deferens with 100 ng/ml relaxin increased the mRNA levels for the cystic fibrosis chloride channel (cystic fibrosis transmembrane regulator) about three times, and doubled mRNA levels for the inducible form of nitric oxide synthase and metalloproteinase 7. These results suggest that locally produced relaxin acts as an autocrine or paracrine agent in the testis and vas deferens to affect spermatogenesis and seminal fluid composition.

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Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Rat Efferent Duct Epithelium1

Cited by 20 publications

References 33 publications

Effects of the Antiestrogen Fulvestrant (ICI 182,780) on Gene Expression of the Rat Efferent Ductules1

Effects of the Antiestrogen Fulvestrant (ICI 182,780) on Gene Expression of the Rat Efferent Ductules1

Signal Transduction in the Ductuli Efferentes Testis of the Rat: Inhibition of Fluid Reabsorption by Cyclic Adenosine 3′, 5′-Monophosphate1

Locally produced relaxin may affect testis and vas deferens function in rats

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