Androgen ablation results in differential regulation of transforming growth factor-beta isoforms in rat male accessory sex organs and epididymis

Desai, Kartiki V.; Kondaiah, Paturu

doi:10.1677/jme.0.0240253

Cited by 42 publications

(34 citation statements)

References 29 publications

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“…Differential expression profiles for TGF-b isoforms (TGF-b1, TGF-b2, and TGF-b3) have previously been characterized in the rat epididymis by northern blot (Desai et al 1998, Desai & Kondaiah 2000. In these studies, substantial TGF-b1 expression was observed compared with other isoforms; TGF-b1 expression was upregulated in the caput, corpus, and cauda epididymides following total androgen ablation by orchidectomy.…”

Section: Growth Factor Systems In the Epididymismentioning

confidence: 99%

Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5α-reductase inhibition

Henderson¹,

Cooke²,

Robaire³

2006

Journal of Endocrinology

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Dihydrotestosterone (DHT) is the primary androgen acting in the epididymis, the site of sperm maturation. Previously, we showed that the treatment of male rats with PNU157706, an inhibitor that acts on both isoforms of 5a-reductase to prevent DHT formation, has effects on the expression of genes implicated in processes that create the optimal luminal microenvironment required for sperm maturation, and on sperm maturation itself. However, signaling pathways involved in regulating or mediating DHT actions in the epididymis remain largely unknown. The goals of this study were to determine the expression profiles of potential signaling systems in the epididymis and assess their DHTdependence using two different dual 5a-reductase inhibitors. Rats were untreated or gavaged with vehicle, 10 mg/kg per day PNU157706 or 32 mg/kg per day FK143 for 28 days and epididymal gene expression was analyzed. Gene array analysis revealed analogous effects of FK143 on overall epididymal gene expression when compared with previous PNU157706 studies. Quantitative RT-PCR analysis of the expression of the 5a-reductase isozymes, androgen receptor, and members of the IGF, FGF, TGF, and VEGF families revealed novel region-specific expression profiles in the epididymis that were differentially affected by 5a-reductase inhibition; the two inhibitors had parallel effects. Specifically, in proximal regions, 5a-reductase 1, androgen receptor, and TGF-b1 expression increased after treatment, while in distal regions expression of IGF-I, IGFBP-5, IGFBP-6, and FGF-10 decreased. These results provide insight into epididymal signaling mechanisms and indicate potential candidates acting either upstream or downstream of DHT to regulate and/or mediate its actions in the epididymis.

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Section: Growth Factor Systems In the Epididymismentioning

confidence: 99%

Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5α-reductase inhibition

Henderson¹,

Cooke²,

Robaire³

2006

Journal of Endocrinology

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“…(36) Furthermore, androgen ablation is found to induce expression of each of the three TGFb isoforms in an isoform-and tissue-specific manner in the seminal vesicle and epididymis. (37) Whole organ culture of neonatal seminal vesicles with TGFb1 inhibits androgen-induced epithelial branching and suppresses protein and mRNA synthesis; however, TGFb1 does not affect seminal vesicle growth in the absence of androgens. (38) Interest in the role of TGFb in the prostate stems from its likely involvement in prostate cancer.…”

Section: Testis Function and Spermatogenesismentioning

confidence: 99%

Defining the actions of transforming growth factor beta in reproduction

2002

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Members of the transforming growth factor beta (TGFbeta) family are pleiotropic cytokines with key roles in tissue morphogenesis and growth. TGFbeta1, TGFbeta2 and TGFbeta3 are abundant in mammalian reproductive tissues, where development and cyclic remodelling continue in post-natal and adult life. Potential roles for TGFbeta have been identified in gonad and secondary sex organ development, spermatogenesis and ovarian function, immunoregulation of pregnancy, embryo implantation and placental development. However, better tools must now be employed to map more precisely essential functions and the regulatory networks governing their activity. Gene ablation and transgenic models are expected to provide novel insights into distinct physiological activities for each TGFbeta isoform in normal reproductive function and reproductive pathologies. It is also necessary to consider the mechanisms controlling TGFbeta activation from latent precursor forms, and receptor and binding protein expression. Smad intracellular signalling circuitry and modulation by environmental stimuli through cross-talk with other signal transduction pathways will further constrain TGFbeta action. This review examines existing evidence for TGFbeta1, TGFbeta2 and TGFbeta3 regulation of male and female reproductive biology, and highlights prospects for future research.

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“…On the other hand, testosterone administration to intact or castrated rats results in benign and/or atypical prostatic hyperplasia (Colombel and Buttyan 1995). Testosterone regulates the expression of various growth factors and their receptors, including epidermal growth factor (EGF) and EGF receptor, transforming growth factors (TGFs), TGF-α, TGF-β1, TGF-β2, and TGF-β3 and TGF-β type II receptor, basic fibroblast growth factor (bFGF) and FGF receptor I, hepatocyte growth factor (HGF), and HGF receptor, keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF) in the rat prostate Hägg-ström et al 1999;Desai and Kondaiah 2000).…”

Section: Introductionmentioning

confidence: 99%

The effect of castration on endothelins, their receptors and endothelin converting enzyme in rat prostate

Takahashi

Afiatpour

Foster

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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We previously have shown that experimental diabetes in rats causes prostatic involution, reduces serum testosterone levels, and causes an upregulation in prostatic endothelin (ET) receptors. Furthermore, insulin treatment normalizes these changes (Saito et al., Mol Cell Biochem 210:1-12, 2000). Since experimental diabetes-induced reduction in serum testosterone may be a factor in the alteration of the ET receptors and of prostatic growth, we investigated the effect of castration, another means of involuting the prostate and decreasing serum testosterone levels, on the expression of ET receptors in ventral and dorsolateral regions of the rat prostate.Three-month-old Sprague-Dawley rats were surgically castrated or sham operated, and then killed on the 7th post-operative day. Biochemical and pharmacological properties, and localization of ET receptors in the rat prostate, were determined by performing a series of binding experiments with [(125)I]ET-1 and by light microscopy autoradiography, respectively. The expression levels of ET-1, ET-3, ET receptor subtypes and endothelin converting enzyme-1 (ECE-1) mRNAs were assessed by relative multiplex reverse transcription polymerase chain reaction (RT-PCR). The total density of ET receptors increases 3.7-fold in the ventral and 2.1-fold in the dorsolateral regions of the castrated rat prostate compared to sham operated animals. Castration causes a 2.4-fold increase in the density of alpha(1)-adrenoceptors (alpha(1)-ARs) in the ventral region of the prostate, but no change in the density of alpha(1)-ARs in the dorsolateral region of the rat prostate. The predominant ET receptor subtype in the rat prostate is the ETA subtype, which is mainly located in the prostatic stroma. In addition, RT-PCR data show an upregulation in the expression of ETB receptor subtype, ET-1 and ECE-1 mRNA in both regions, and a downregulation in the expression of ETA receptor subtype mRNA in the dorsolateral region of the castrated rat prostate. There is no change in the expression of ET-3 mRNA in either region. Castration does not cause significant changes in the pharmacological properties of prostatic ET receptors, i.e., the predominance of ETA receptors in either region of the prostate, or the expression of ETA receptor subtype mRNA in the ventral region of the castrated rat prostate. These results suggest the existence of a region/lobe-specific regulatory role for testosterone in the expression of the ET receptor system in the rat prostate.

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Androgen ablation results in differential regulation of transforming growth factor-beta isoforms in rat male accessory sex organs and epididymis

Cited by 42 publications

References 29 publications

Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5α-reductase inhibition

Region-specific expression of androgen and growth factor pathway genes in the rat epididymis and the effects of dual 5α-reductase inhibition

Defining the actions of transforming growth factor beta in reproduction

The effect of castration on endothelins, their receptors and endothelin converting enzyme in rat prostate

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