Cell Growth Effects of Triiodothyronine and Expression of Thyroid Hormone Receptor in Prostate Carcinoma Cells

Hsieh, Ming‐Li; Juang, Horng‐Heng

doi:10.2164/jandrol.04162

Cited by 38 publications

(32 citation statements)

References 32 publications

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“…This suggestion is supported by unpublished data from our laboratory showing that regular sexual activity is accompanied by a significant increase in D1 activity. Although the presence of thyroid hormone receptors has not been described in normal prostate tissue, recent reports indicate their presence in the cancer human cell line (Hsieh & Juang 2005).…”

Section: Discussionmentioning

confidence: 99%

Deiodinase type 1 activity is expressed in the prostate of pubescent rats and is modulated by thyroid hormones, prolactin and sex hormones

Anguiano¹,

López²,

Delgado³

et al. 2006

Journal of Endocrinology

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The aim of this study was to characterize the type of 5 0 -deiodinase activity in the prostate of pubescent rats (7-8 weeks), to establish its distribution in the lobes (ventral, dorsolateral, and anterior), and to analyze its modulation by prolactin (PRL), testosterone, dihydrotestosterone (DHT), and 17b-estradiol (E 2 ). Our results showed that the enzymatic activity was highly susceptible to inhibition by 6-n-propyl-2-thiouracil and gold thioglucose, its preferential substrate was reverse tri-iodothyronine (rT 3 ), it exhibited a low dithiothreitol requirement (5 mM), and the apparent K m and V max values for substrate (rT 3 ) were approximately 0$25 mM and 9$0 pmol liberated/mg protein per hour, respectively. All these characteristics indicate the preferential expression of type 1 deiodinase (D1), which was corroborated by demonstrating the presence of D1 mRNA in prostate.D1 activity was detected in all lobes and was most abundant in the dorsolateral. Although we detected type 2 deiodinase (D2) mRNA expression, the D2 activity was almost undetectable. D1 activity was enhanced in animals with hyperthyroidism and hyperprolactinemia, in intact animals treated with finasteride (inhibitor of local DHT production), and in castrated animals with E 2 replacement. In contrast, activity diminished in castrated animals with testosterone replacement. Our results suggest that thyroid hormones, PRL, and E 2 exert a positive modulation on D1 activity, while testosterone and DHT exhibit an inhibitory effect. D1 activity may be associated with prostate maturation and/or function.

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Section: Discussionmentioning

confidence: 99%

Deiodinase type 1 activity is expressed in the prostate of pubescent rats and is modulated by thyroid hormones, prolactin and sex hormones

Anguiano¹,

López²,

Delgado³

et al. 2006

Journal of Endocrinology

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“…As mentioned before, this unresponsiveness could be related to the dedifferentiated state and/or the invasive capacity of these cells. TRβ1, the nuclear thyroid receptor, has been identified in both LNCaP and DU145 cells (29); however, T3 exerts proliferative effects only in LNCaP cells (27,62). Overall, our data in vitro and in vivo indicate that T3 restrains cancer progression mediated by β-adrenergic receptors in a model of differentiated cancer.…”

Section: Discussionmentioning

confidence: 56%

Triiodothyronine Attenuates Prostate Cancer Progression Mediated by β-Adrenergic Stimulation

Delgado‐González

Sánchez-Tusié

Morales

et al. 2016

Mol Med

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Prostate cancer cells are responsive to adrenergic and thyroid stimuli. It is well established that β-adrenergic activation (protein kinase A [PKA]/cAMP response element binding protein [CREB]) promotes cancer progression, but the role of thyroid hormones is poorly understood. We analyzed the effects of β-adrenergic stimulation (isoproterenol [ISO]) and/or thyroid hormone on neuroendocrine (NE) differentiation and cell invasion, using in vivo (LNCaP tumor) and in vitro models (LNCaP and DU145 human cells). Nude mice were inoculated with LNCaP cells and were treated for 6 wks with ISO (200 μg/d), triiodothyronine (T3, 2.5 μg/d) or both. ISO alone reduced tumor growth but increased tumor expression of cAMP response element (CRE)-dependent genes (real-time polymerase chain reaction, chromogranin A, neuron-specific enolase, survivin, vascular endothelial growth factor [VEGF], urokinase plasmin activator [uPA] and metalloproteinase-9 [MMP-9]) and some proteins related to NE differentiation and/or invasiveness (synaptophysin, VEGF, pCREB). T3 reduced tumor growth and prevented the overexpression of ISO-stimulated factors through a pCREB-independent mechanism. In low invasive LNCaP cells, 50 μmol/L ISO or 100 nmol/L thyroxine (T4) induced the acquisition of NE-like morphology (phase-contrast microscopy), increased VEGF secretion (ELISA) and invasive capacity (Transwell assay), but no synergistic effects were observed after the coadministration of ISO + T4. In contrast, 10 nmol/L T3 alone had no effect, but it prevented the NE-like morphology and invasiveness stimulated by ISO. None of these treatments had any effect on highly invasive DU145 cells. In summary, this study showed that ISO and T4 increase cancer progression, and T3 attenuates ISO-stimulated progression. Further studies are required to determine if changes in the ratio of T4/T3 could be relevant for prostate cancer progression.

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“…[18,19,47,48], and, second, as a modulating factor to maintain the integrity and differentiation of prostate epithelium. First, T 3 directly stimulates glycosidase activity in normal prostate [14,15]; second, T 3 and androgens have synergistic effects on proliferation and expression of prostate-specific antigen in the differentiated tumoral cell line LNCaP [49]; and, third, there is a decrease of D1 activity (unpublished data) and a loss of responsiveness to T3 in the dedifferentiated prostate cancer cell line DU145 [50]. Moreover, and in relation with pathologies, recent studies have shown that hypertensive patients exhibited a high risk of developing prostate cancer [51]; however, in many of these patients, the associated thyroid disease was hypothyroidism [52], suggesting a paradoxical dissociation of these components.…”

Section: Discussionmentioning

confidence: 96%

Postejaculatory Increase of Prostatic Triiodothyronine (T3) Depends on Sympathetic Innervation in the Rat1

Delgado‐González

Aceves

Anguiano

2011

Biology of Reproduction

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Thyronines are essential for the development of the male reproductive system, including the prostate gland. Metabolically active 3,5,3' triiodothyronine (T(3)) is generated mainly by the extrathyroidal, enzymatic 5'deiodination of the prohormone thyroxine (T(4)), which is catalyzed by deiodinases type 1 (D1) and type 2 (D2). Prostate D1 activity is highly expressed during puberty and declines with age, but continuous, long-term sexual activity prevents this reduction. The aims of this study were to characterize the changes in prostatic D1 activity in response to consecutive ejaculations and to determine whether sympathetic input participates in the local T(3) generation (D1 activity). D1 activity was analyzed in prostates of sexually experienced, 4-mo-old male rats after one to five ejaculations. D1 activity, T(3) concentrations, and the T(3)-dependent gene ornithine decarboxylase (Odc) were measured after the fourth ejaculation in prostates of intact, sham, and sympathectomized (Smpx, hypogastric nerve) rats. D1 activity was evaluated by the radio-iodine-release method; T(3) was measured by radioimmunoassay and Odc expression by real-time PCR. Data showed a gradual increase of prostate D1 activity in response to consecutive ejaculations. The highest activity was found after the fourth ejaculation, and it decreased after the fifth. The increase of prostate D1 activity after ejaculation was blocked in Smpx males as compared to intact or sham animals. The changes in D1 activity correlate with prostatic T(3) concentrations and Odc expression. Circulating levels of T(3) were not affected by consecutive ejaculations or by Smpx. These findings indicate that the postejaculatory increase in prostatic generation of T(3) depends on sympathetic input.

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Cell Growth Effects of Triiodothyronine and Expression of Thyroid Hormone Receptor in Prostate Carcinoma Cells

Cited by 38 publications

References 32 publications

Deiodinase type 1 activity is expressed in the prostate of pubescent rats and is modulated by thyroid hormones, prolactin and sex hormones

Deiodinase type 1 activity is expressed in the prostate of pubescent rats and is modulated by thyroid hormones, prolactin and sex hormones

Triiodothyronine Attenuates Prostate Cancer Progression Mediated by β-Adrenergic Stimulation

Postejaculatory Increase of Prostatic Triiodothyronine (T3) Depends on Sympathetic Innervation in the Rat1

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