Sex steroids modulate α<sub>1</sub>‐adrenoceptor‐stimulated Ca<sup>2+</sup> elevation in human cultured prostatic stromal cells

Nguyen, Son Thanh; Prakash, Roshan; Anderson, Caroline; Frydenberg, Mark; Haynes, John M.

doi:10.1002/pros.20504

Cited by 7 publications

(13 citation statements)

References 31 publications

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“…In cultured neurons, we have found that flutamide antagonizes classic genomic actions of T and DHT but mimics rather than blocks the nongenomic neuroprotective actions of these androgens [230]. Of particular interest are novel compounds that bind AR but have altered interactions with AR binding pocket side chains that underlie tissue specificity.…”

Section: Emerging Strategies Of Hormone-related Therapies In Alzhmentioning

confidence: 99%

Protective actions of sex steroid hormones in Alzheimer’s disease

Pike

Carroll

Rosario

et al. 2009

Frontiers in Neuroendocrinology

447

356

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Risk for Alzheimer’s disease (AD) is associated with age-related loss of sex steroid hormones in both women and men. In postmenopausal women, the precipitous depletion of estrogens and progestogens is hypothesized to increase susceptibility to AD pathogenesis, a concept largely supported by epidemiological evidence but refuted by some clinical findings. Experimental evidence suggests that estrogens have numerous neuroprotective actions relevant to prevention of AD, in particular promotion of neuron viability and reduction of β-amyloid accumulation, a critical factor in the initiation and progression of AD. Recent findings suggest neural responsiveness to estrogen can diminish with age, reducing neuroprotective actions of estrogen and, consequently, potentially limiting the utility of hormone therapies in aged women. In addition, estrogen neuroprotective actions are also modulated by progestogens. Specifically, continuous progestogen exposure is associated with inhibition of estrogen actions whereas cyclic delivery of progestogens may enhance neural benefits of estrogen. In recent years, emerging literature has begun to elucidate a parallel relationship of sex steroid hormones and AD risk in men. Normal age-related testosterone loss in men is associated with increased risk to several diseases including AD. Like estrogen, testosterone has been established as an endogenous neuroprotective factor that not only increases neuronal resilience against AD-related insults, but also reduces β- amyloid accumulation. Androgen neuroprotective effects are mediated both directly by activation of androgen pathways and indirectly by aromatization to estradiol and initiation of protective estrogen signaling mechanisms. The successful use of hormone therapies in aging men and women to delay, prevent, and or treat AD will require additional research to optimize key parameters of hormone therapy and may benefit from the continuing development of selective estrogen and androgen receptor modulators.

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Section: Emerging Strategies Of Hormone-related Therapies In Alzhmentioning

confidence: 99%

Protective actions of sex steroid hormones in Alzheimer’s disease

Pike

Carroll

Rosario

et al. 2009

Frontiers in Neuroendocrinology

447

356

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“…More recent cell culture experiments have also shown that sex hormones have varied effects on prostate smooth muscle cell contractility. Slight changes in the ratio of androgen to oestrogen have been shown to result in dramatic changes in calcium influx in prostatic stromal cells (Nguyen et al 2007). Rather than changing ratios, an earlier study used single concentrations of oestradiol and testosterone and found that cell lines from different patients responded differently to hormone treatment, with some lines showing increased myosin expression after testosterone and oestradiol treatment and others showing no change (Smith et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, it has been shown that the expression of smooth muscle cell markers is influenced by oestradiol treatment, however, the same treatment had little impact on the growth of smooth muscle cell cultures (Zhang et al 1997). A recent study, also using cell culture techniques, showed that at certain concentrations, testosterone, oestradiol and dihydrotestosterone, either alone or in combination, influenced the agonist-induced activity of human cultured prostatic stromal cells through regulation of a-and b-adrenoceptors and/or signal transduction pathways (Nguyen et al 2007).…”

Section: Introductionmentioning

confidence: 99%

The effects of targeted deletion of the aromatase enzyme on prostatic contractile responses to noradrenaline in mice

Gray

Short

Simpson³

et al. 2007

Journal of Endocrinology

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This investigation aimed to see whether a change in the oestrogen to androgen ratio alters prostate contractility. Isolated organ bath studies using prostates from aromatase knockout (ArKO) mice which were homozygous (ArKOK/K) and heterozygous (ArKOC/K) for the disrupted aromatase cyp19 gene and wild-type littermates (ArKOC/C) were conducted. The distribution of noradrenergic nerves was visualized using the sucrose-potassium phosphate-glyoxylic acid method. ArKOK/K mice had increased prostate weights compared with ArKOC/C mice. Frequency-response curves to electrical field stimulation (EFS; 0 . 5 ms pulse duration, 60 V, 0 . 1-20 Hz) yielded frequency-dependent contractions, while noradrenaline (10 nM-1 mM) and tyramine (1 mM-1 mM) produced concentration-dependent contractions. Prazosin (0 . 3 mM) attenuated the responses induced by noradrenaline and EFS in all mice (P%0 . 019, nZ5-7), while cocaine (10 mM) attenuated the responses evoked by tyramine (P!0 . 001, nZ6). There were no genotype differences in EFS-and noradrenaline-induced responses (PR0 . 506, nZ10-13). Prostates from ArKOK/K and ArKOC/K mice were more sensitive to tyramine than prostates from ArKOC/C mice (P!0 . 001, nZ11-13). Dense adrenergic innervation of the prostate was similar in all mice. These results suggest that although the absence of aromatase increases prostatic growth, this translates only to a subtle and selective increase in contractility in mature mice.

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“…Therefore, this finding indicates that activation of prostate α1‐adrenoceptors is coupled to the signaling of ERK1/2 in the human prostate . α 1 ‐Adrenoceptor antagonists are used to treat BPH, as pharmacological α 1 ‐adrenocepto blockade, thought to relax prostatic and bladder neck smooth muscle tone, has been shown to increase urinary flow rate and improve symptoms in BPH patients …”

Section: Introductionmentioning

confidence: 97%

Cyclic guanosine monophosphate‐enhancing reduces androgenic extracellular regulated protein kinases‐phosphorylation/Rho kinase II‐activation in benign prostate hyperplasia

Liu

Fan

et al. 2013

Int J of Urology

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Abbreviations & Acronyms BPH = benign prostatic hyperplasia cGMP = cyclic guanosine monophosphate, protein kinase c-Ras = rat sarcoma CTL = control group DHT = dihydroxy testosterone ERK = extracellular regulated protein kinases IGFR = insulin growth factor receptor Objectives: To investigate whether 7-[2-[4-(2-chlorophenyl) piperazinyl] ethyl]-1,3-dimethylxanthine (KMUP-1) inhibits the effects of testosterone on the development of benign prostatic hyperplasia and sensitizes prostate contraction. Methods: A benign prostatic hyperplasia animal model was established by subcutaneous injections of testosterone (3 mg/kg/day, s.c.) for 4 weeks in adult male Sprague-Dawley rats. Animals were divided into six groups: control, testosterone, testosterone with KMUP-1 (2.5, 5 mg/kg/day), sildenafil (5 mg/kg/day) or doxazosin (5 mg/kg/day). After 4 weeks, the animals were killed, and prostate tissues were prepared for isometric tension measurement and western blotting analysis. KMUP-1, Y27632, zaprinast, doxazosin or tamsulosin were used at various concentrations to determine the contractility sensitized by phenylephrine (10 μmol/L). Results: KMUP-1 inhibited testosterone-induced phosphorylation of extracellular signalregulated phosphorylated protein kinase and mitogen-activated protein kinase kinase and Rho kinase-II activation. Sildenafil and doxazosin significantly decreased benign prostatic hyperplasia-induced mitogen-activated protein kinase kinase and Rho kinase-II activation. The decreased expressions of soluble guanylate cyclase α1 was reversed by KMUP-1, doxazosin and sildenafil. Soluble guanylate cyclase β1 and protein kinase G were increased by KMUP-1, doxazosin, and sildenafil in the testosterone-treated benign prostatic hyperplasia group. Phosphodiesterase-5A was increased by testosterone and inhibited by KMUP-1 (5 mg/kg/day) or sildenafil (5 mg/kg/day). KMUP-1 inhibited phenylephrine-sensitized prostate contraction of rats treated with testosterone. Conclusions: Mitogen-activated protein kinase 1/extracellular regulated protein kinases kinase, soluble guanylate cyclase/cyclic guanosine monophosphate, protein kinase/protein kinase G and Rho kinase-II are related to prostate smooth muscle tone and proliferation induced by testosterone. KMUP-1 inhibits testosterone-induced prostate hyper-contractility and mitogen-activated protein kinase 1/extracellular regulated protein kinases kinasephosphorylation, and it inactivates Rho kinase-II by cyclic guanosine monophosphate, protein kinase and α1A-adenergic blockade. Thus, KMUP-1 might be a beneficial pharmacotherapy for benign prostatic hyperplasia.

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Sex steroids modulate α₁‐adrenoceptor‐stimulated Ca²⁺ elevation in human cultured prostatic stromal cells

Abstract: These results indicate that sex steroids modulate the activities of HCPSCs through the regulation of both receptors and signal transduction processes.

Cited by 7 publications

References 31 publications

Protective actions of sex steroid hormones in Alzheimer’s disease

Protective actions of sex steroid hormones in Alzheimer’s disease

The effects of targeted deletion of the aromatase enzyme on prostatic contractile responses to noradrenaline in mice

Cyclic guanosine monophosphate‐enhancing reduces androgenic extracellular regulated protein kinases‐phosphorylation/Rho kinase II‐activation in benign prostate hyperplasia

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Sex steroids modulate α1‐adrenoceptor‐stimulated Ca2+ elevation in human cultured prostatic stromal cells

Abstract: These results indicate that sex steroids modulate the activities of HCPSCs through the regulation of both receptors and signal transduction processes.

Cited by 7 publications

References 31 publications

Protective actions of sex steroid hormones in Alzheimer’s disease

Protective actions of sex steroid hormones in Alzheimer’s disease

The effects of targeted deletion of the aromatase enzyme on prostatic contractile responses to noradrenaline in mice

Cyclic guanosine monophosphate‐enhancing reduces androgenic extracellular regulated protein kinases‐phosphorylation/Rho kinase II‐activation in benign prostate hyperplasia

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Product

Resources

About

Sex steroids modulate α₁‐adrenoceptor‐stimulated Ca²⁺ elevation in human cultured prostatic stromal cells