The effect of oxytocin on cell proliferation in the human prostate is modulated by gonadal steroids: implications for benign prostatic hyperplasia and carcinoma of the prostate

Whittington, Kate; Connors, Belinda; King, Keith; Assinder, Steve; Hogarth, K. J.; Nicholson, Helen

doi:10.1002/pros.20612

Cited by 41 publications

(28 citation statements)

References 37 publications

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“…Oxytocin and its signaling pathway have been shown to inhibit growth of neoplastic cells, such as ovarial, neuroblastoma, astrocytoma, and other cell types (4). Oxytocin concentrations were shown to be increased in benign and decreased in malignant prostate disease, and changes in prostatic concentrations of oxytocin may facilitate cell proliferation (31). Oxytocin receptor is downregulated in non-small cell lung, and its ectopical expression suppresses cell growth (32).…”

Section: Discussionmentioning

confidence: 99%

Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men

Clodi

Vila²,

Geyeregger³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

146

131

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2008; doi:10.1152/ajpendo.90263.2008.-Oxytocin is a hormone and neurotransmitter found to have anti-inflammatory functions in rodents. Here we used experimental bacterial endotoxinemia to examine the role of exogenous oxytocin administration on innate immune responses in humans. Ten healthy men received, in a randomized, placebo-controlled, crossover design, placebo, oxytocin, LPS, and LPS ϩ oxytocin. Oxytocin treatment resulted in a transient or prolonged reduction of endotoxin-induced increases in plasma ACTH, cortisol, procalcitonin, TNF-␣, IL-1 receptor antagonist, IL-4, IL-6, macrophage inflammatory protein-1␣, macrophage inflammatory protein-1␤, monocyte chemoattractant protein-1 (MCP-1), interferoninducible protein 10, and VEGF. In vitro, oxytocin had no impact on LPS effects in releasing TNF-␣, IL-6, and MCP-1 in monocytes and peripheral blood mononuclear cells from healthy human donors. In summary, oxytocin decreases the neuroendocrine and cytokine activation caused by bacterial endotoxin in men, possibly due to the pharmacological modulation of the cholinergic anti-inflammatory pathway. Oxytocin might be a candidate for the therapy of inflammatory diseases and conditions associated with high cytokine and VEGF levels.neuroendocrinology; hypothalamic-pituitary-adrenal; cytokines SYSTEMIC INFLAMMATION IS IMPLICATED in the pathophysiology of many diseases, including chronic inflammatory diseases, infections, sepsis, atherosclerosis, and obesity (11,13,22,25). The most widely used model for testing the systemic host response to infection and inflammation in humans is the intravenous administration of bacterial endotoxin, which contains LPS parts of the Escherichia coli bacterial wall (8). Human response mechanisms to this challenge are integrated via coordinated neuroendocrine-immune interactions (5, 9, 30).Physiological conditions associated with a reduced hypothalamic-pituitary-adrenal (HPA) response to different stressors include the peripartal period and lactation (12,26). Common denominators of these conditions are high intrahypothalamic and plasma oxytocin concentrations. Oxytocin is a highly conserved nonapeptide with hormone and neurotransmitter properties that is synthesized in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus (10). It exerts direct excitatory effects on vagal neurons and has classic reproduction-related functions (1,14,20).A large body of evidence suggests a regulatory role of oxytocin during immune and inflammatory responses in animal models. Oxytocin displays anti-inflammatory effects, abolishes the sepsis-induced increase in TNF-␣, and protects against multiple organ damage (6, 7, 16, 24). In contrast, oxytocindeficient mice exhibit increased stress responses associated with a significant hyperactivation of the HPA axis (2).Here we present a randomized, placebo-controlled, crossover trial, conducted to test the effect of continuous intravenous oxytocin infusion on LPS-induced systemic inflammation in 10 healthy men. In addition, we investigated whether ...

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Section: Discussionmentioning

confidence: 99%

Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men

Clodi

Vila²,

Geyeregger³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

146

131

View full text Add to dashboard Cite

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“…Oxytocin receptors are expressed in a large majority of human ovarian carcinoma tissue, and cancer cell proliferation, migration, and invasion are inhibited by oxytocin treatment in vitro and in vivo in mice (Morita et al, 2004). Whittington et al (2007) noted that oxytocin concentrations were increased in benign and decreased in malignant prostate disease, and changes in oxytocin concentrations in the prostate may facilitate cell proliferation. Along with the fact that oxytocin can inhibit proangiogenic molecules such as vascular endothelial growth factor in healthy men (Clodi et al, 2008), there may be a biological role for oxytocin in cancer progression (further discussed in Cassoni et al, 2004).…”

Section: Immune System and Physical Healthmentioning

confidence: 99%

Salubrious effects of oxytocin on social stress-induced deficits

Smith

Wang

2012

Hormones and Behavior

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Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health.

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“…2B). A significant increase in cell migration was observed when PC3 and PC3M were treated with OXT at the low dose of 1 nM (32). As shown in Fig 3, the effect of OXT (100 nM) was completely inhibited by pretreatment of PC3M cells with a specific OXTR antagonist (L-371,267; 1 μM).…”

Section: Resultsmentioning

confidence: 99%

Oxytocin Induces the Migration of Prostate Cancer Cells: Involvement of the Gi-Coupled Signaling Pathway

Zhong

Boseman

Millena

et al. 2010

Molecular Cancer Research

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Expression of genes that encode oxytocin (OXT) and vasopressin (AVP) and their cognate receptors in normal and diseased prostates are only partially characterized. Reverse transcription and PCR were used to examine the expression of these genes in normal prostate epithelial and stromal cell lines, k-ras-transformed prostate epithelial cell lines, and in four prostate cancer cell lines. Secreted and cell-associated OXT peptide was measured by an enzyme immunoassay. OXT and its receptor (OXTR) were expressed in all eight prostate cell lines. Cellassociated OXT peptide was also found in all prostate epithelial cell lines except in DU145 cells. Neither AVP nor its cognate receptors (V1a receptor and V2 receptor) were expressed in any prostate cell line examined. These data point to the OXTR as the primary target of OXT and AVP, and suggest that OXT might be an autocrine/paracrine regulator in human prostate. We found that OXT induces the migration of PC3 and PC3M, but not DU145 prostate cancer cells. The effect of OXT is distinct from the epidermal growth factor (EGF)-induced migration of prostate cancer cells, in which ERK1/2 and EGF receptor kinase activities were required. When cells were pretreated with pertussis toxin, the effect of OXT, but not EGF, on cell migration was abolished. Pretreatment with the cyclic AMP analogue, 8-Br-cAMP, did not affect OXT-induced cell migration, which eliminated the nonspecific effect of pertussis toxin. We conclude that a Gi-dependent mechanism is involved in OXTR-mediated migration of prostate cancer cells, and indicates a role for OXTR in prostate cancer metastasis. Mol Cancer Res; 8(8); 1164-72. ©2010 AACR.

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The effect of oxytocin on cell proliferation in the human prostate is modulated by gonadal steroids: implications for benign prostatic hyperplasia and carcinoma of the prostate

Abstract: Changes in prostatic concentrations of OT that occur with aging and malignant disease may act to facilitate cell proliferation. The localization of the OT receptor within the plasma membrane modulates OT's proliferative response in the prostate.

Cited by 41 publications

References 37 publications

Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men

Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men

Salubrious effects of oxytocin on social stress-induced deficits

Oxytocin Induces the Migration of Prostate Cancer Cells: Involvement of the Gi-Coupled Signaling Pathway

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