Role of 5α-reductase inhibitors in benign prostatic diseases

Azzouni, Faris; Mohler, James L.

doi:10.1038/pcan.2012.1

Cited by 32 publications

(34 citation statements)

References 71 publications

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“…These data correlate well with the concept that inhibition of DHT production in the prostate triggers apoptosis without affecting DHT-stimulated cellular proliferation [100] (Figure 1), and in agreement with the evidence that patients with 5α-reductase deficiencies never develop prostate cancer [53,101]. Five milligrams daily of finasteride for four years produced a significant reduction in serum levels of DHT [102,103].…”

Section: Finasteridesupporting

confidence: 87%

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

Minutoli

Rinaldi

Marini

et al. 2016

IJMS

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Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

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Section: Finasteridesupporting

confidence: 87%

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

Minutoli

Rinaldi

Marini

et al. 2016

IJMS

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“…Pokazano je takođe da ALLO i THDOC ispoljavaju anksiolitičko i antidepresivno dejstvo (9). Finasterid (FIN), inhibitor 5α-reduktaze, primenjuje se u terapiji hiperplazije prostate (10) i androgene alopecije (11). Ovaj inhibitor smanjuje unos etanola kod miševa kod kojih se razvila zavisnost (12), izaziva hiperalgeziju (13), deluje proepileptogeno (14, 15) i poboljšava tok hepatične encefalopatije (HE) (16).…”

Section: Uvodunclassified

The effect of finasteride on anxiety in rats

Vasović¹

2016

Medicinski podmladak

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SažetakUvod: Tradicionalni neurobiološki koncept etiologije anksioznih poremećaja zasnovan je na monoaminergičkoj hipotezi, prema kojoj je poremećaj prouzrokovan deficitom serotoninergičke, odnosno noradrenergičke transmisije u funkcionalno važnim delovima mozga. Skorašnje studije su ukazale na značaj uloge gama aminobuterne kiseline (GABA) u nastanku ovog poremećaja. Blokadom 5α-reduktaze u mozgu, finasterid (FIN) inhibira sintezu alopregnanolona (ALLO) i tetrahidrodeoksi-kortikosterona (THDOC) na dozno zavisan način i preusmerava progesteron u alternativne metaboličke puteve čime menja GABA-ergičku transmisiju i utiče na emocionalno stanje. Cilj: Cilj ovog rada bio je da ispita uticaj finasterida, kao modulatora GABA-ergičke transmisije, na anksioznost kod pacova. Materijal i metode: Mužjaci pacova Vistar (Wistar) soja podeljeni su u dve grupe. Prva, kontrolna grupa tretirana je 2-hidroksipropil-ß-ciklodekstrinom, a druga grupa je tretirana finasteridom (150 mg/kg). Dnevne doze FIN-a (50 mg/kg) administrirane su intraperitonealno tokom tri uzastopna dana. Anksioznost je procenjivana 24 časa nakon primene poslednje doze FIN-a "uzdignutim plus lavirintom" i testom "svetlo-tama". Rezultati: U testu "uzdignuti plus lavirint" ukupno vreme provedeno u otvorenim kracima lavirinta nije se značajno razlikovalo kod životinja iz grupe tretirane FIN-om u odnosu na životinje iz kontrolne grupe (p > 0,05). Nije uočena ni značajna razlika između dve grupe u broju prelazaka iz jednog kraka u drugi preko centralne platforme (p > 0,05). U testu "svetlosttama" vreme koje su životinje iz FIN grupe provodile u svetlom delu kutije bilo je značajno kraće u odnosu na isti parametar registrovan kod životinja iz kontrolne grupe (p < 0,05). Zaključak: Finasterid ispoljava anksiogeno dejstvo kod pacova koje se prvenstveno ispoljava anksioznošću od svetlog prostora. Finasterid nema značajan uticaj na anksioznost od otvorenog prostora. Ključne reči: Anksioznost, finasterid, neurosteroidi, GABA, pacovi AbstractIntroduction: The traditional neurobiological concept of the etiology of anxiety disorders is based on the monoamine hypothesis, which suggests that mood disorders are caused by a deficiency in serotonin or noradrenaline transmission at functionally important receptors in the brain. Recent studies have provided strong evidence that gamma-aminobutyric acid (GABA) is involved in the pathophysiology of the anxiety as well. By blocking 5α-reductase in the brain, finasteride (FIN) inhibits the synthesis of allopregnanolone (ALLO) and tetrahydrodeoxy-corticosterone (THDOC) in a dose-dependent manner and redirects progesterone to alternative metabolic pathways, the effects that change GABAergic transmission and affect the emotional state. Aim: The aim of this study was to investigate the effect of finasteride as GABAergic transmission modulator, on anxiety in rats. Materials and methods: Male Wistar rats were divided into the groups: 1. control treated with 2-hydroxypropyl-β-cyclodextrin; 2. finasteride-treated, FIN (150 mg/kg). Daily doses ...

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“…1 The prostate is a hormone-responsive organ, and androgen receptor (AR) signalling plays a fundamental role in BPH progression. 3 However, clinical progression still occurs in more than 17% of BPH patients who receive long-term 5-ARI treatment, and the detailed molecular and cellular mechanisms remain to be determined. 2 Reducing androgen levels has been universally recognized as an effective method for treating BPH by inducing prostate epithelial cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

5‐ARI induces autophagy of prostate epithelial cells through suppressing IGF‐1 expression in prostate fibroblasts

et al. 2019

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Objectives: 5α-reductase inhibitor (5-ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment. Materials and Methods:Prostate specimens from patients were collected. Insulinlike growth factor 1 (IGF-1), Beclin-1, LC3 levels, was analysed by immunohistochemistry. The role IGF-1 on autophagic flux in prostate epithelial cells was studied.Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated. Results:We demonstrated that IGF-1 expression is down-regulated in prostate fibroblasts after long-term 5-ARI application. A decrease in IGF-1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF-1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long-term 5-ARI application reduces IGF-1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression. Conclusions:Focusing on the autophagy induced by low levels of IGF-1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information may be found online in the Supporting Information section at the end of the article.How to cite this article: Yang B-Y, Jiang C-Y, Dai C-Y, et al. 5-ARI induces autophagy of prostate epithelial cells throughsuppressing IGF-1 expression in prostate fibroblasts. Cell

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Role of 5α-reductase inhibitors in benign prostatic diseases

Cited by 32 publications

References 71 publications

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

The effect of finasteride on anxiety in rats

5‐ARI induces autophagy of prostate epithelial cells through suppressing IGF‐1 expression in prostate fibroblasts

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