Prostate innervation

McVary, Kevin T.; McKenna, Kevin E.; Lee, Chung

doi:10.1002/(sici)1097-0045(1998)8+<2::aid-pros2>3.0.co;2-u

Cited by 111 publications

(65 citation statements)

References 24 publications

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“…Previous work from our lab supports a significant role of the autonomic nervous system in promoting both prostatic hyperplasia and atrophy by selective neural manipulation. 9,10 Clinical findings, which complement our previous animal studies, demonstrate a quantitative relationship between the level of autonomic sympathetic activity and LUTS/BPH in symptomatic men. 11 Thus, the enhanced excitation of the sympathetic nervous system may be a common mechanism underlying BPH and LUTS.…”

Section: Introductionsupporting

confidence: 81%

“…The increase in both intact and denervated Ngf gene expression reflects the bilateral crossover of prostate innervation as previously demonstrated. 10 In addition at P60 the denervated group is further increased 20% over the intact group. At P120, the denervated VP was significantly increased relative to the sham and intact group, while the intact VP showed no significant change in Ngf in comparison to the sham.…”

Section: Discussionmentioning

confidence: 97%

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Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Podlasek

Ghosh²,

Çakır³

et al. 2013

Asian J Androl

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Benign prostatic hyperplasia (BPH) is a serious health concern and is an underlying cause of lower urinary tract symptoms (LUTS) in many men. In affected men, LUTS/BPH is believed to result from benign proliferation of the prostate resulting in bladder outlet obstruction. Postnatal growth of the prostate is controlled via growth factor and endocrine mechanisms. However, little attention had been given to the function of the autonomic nervous system in prostate growth and differentiation. Nerve growth factor (NGF) is a prostatic mitogen that has a trophic role in autonomic sensory end organ interaction. In this study, we examine how the autonomic nervous system influences prostate growth as a function of age by quantifying NGF in the rat ventral prostate (VP) after pelvic ganglionectomy. Unilateral pelvic ganglionectomy was performed on postnatal days 30 (P30), 60 and 120 Sprague-Dawley rats in comparison to sham controls (n539). Semiquantitative RT-PCR, Western blotting and immunohistochemical analysis for NGF were performed on denervated, intact (contralateral side) and sham control VP 7 days after surgery. Ngf RNA expression was significantly increased in the denervated and intact hyperplastic VP. Western blotting showed age-dependent increases in NGF protein at P60 in the contralateral intact VP. NGF was localized in the nerves, basal cells and columnar epithelium of the prostatic ducts. Denervation causes age-dependent increases in NGF in the VP, which is a potential mechanism by which the autonomic nervous system may regulate prostate growth and lead to BPH/LUTS. Asian Journal of Andrology (2013) Keywords: denervation; nerve growth factor; prostate growth; ventral prostate INTRODUCTION Benign prostatic hyperplasia (BPH) is a serious health concern worldwide and is an underlying cause of many lower urinary tract symptoms (LUTS). LUTS is common in aging men and a population based survey performed in five countries reports that ,64% of adults experience at least one LUTS symptom.1 LUTS has a profound impact on social functioning and quality of life in affected men 2,3 with similar effects reported as after a heart attack or stroke.4 BPH can induce acute urinary retention, incontinence, recurrent urinary tract infection or obstructive uropathy. LUTS secondary to BPH generally consists of three components: benign proliferation of the stroma and epithelium, bladder outlet obstruction and symptoms resulting from obstruction.

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Section: Introductionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 97%

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Podlasek

Ghosh²,

Çakır³

et al. 2013

Asian J Androl

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“…The prostate has been demonstrated to be a rich source of ␣ 1 -and ␤ 2 -adrenergic receptors with both adrenergic and cholinergic innervation into the glandular epithelia (34). Moreover, ␤-adrenergic receptor agonists have been implicated in the maintenance of prostate homeostasis and as mitogens for prostatic stromal cells (35).…”

Section: Pka Activation Is Sufficient To Induce Mitotic Arrest In Lncmentioning

confidence: 99%

Activated 3′,5′-Cyclic AMP-dependent Protein Kinase Is Sufficient to Induce Neuroendocrine-like Differentiation of the LNCaP Prostate Tumor Cell Line

Cox¹,

Deeble²,

Bissonette³

et al. 2000

Journal of Biological Chemistry

112

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Neuroendocrine (NE) differentiation within prostate tumors is proposed to be a contributing factor in disease progression. However, the cellular origin and molecular mechanism controlling differentiation of prostatic NE cells are unresolved. The prostate tumor cell line, LNCaP, can reversibly acquire many NE characteristics in response to treatment with ␤-adrenergic receptor agonists and activators of adenylate cyclase. In this study, we demonstrate that these treatments induce protein kinase A (PKA) activation in LNCaP cells and that ectopic expression of a constitutively activated form of the PKA catalytic subunit, CI␣, results in acquisition of NE characteristics, including the extension of neuritic processes, cessation of mitotic activity, and production of neuron-specific enolase. Forskolin-, epinephrine-, and isoproterenol-dependent NE differentiation of LNCaP cells was significantly inhibited by expressing a dominant negative mutant of the PKA regulatory subunit, RI␣. These results demonstrate that prostatic NE differentiation in response to these agents depends on PKA activation, and this signaling pathway may provide a therapeutic target for treating advanced forms of prostate cancer.Efforts to develop novel therapeutic strategies for treating advanced prostate cancer have resulted in a considerable interest in the potential role of prostatic neuroendocrine (NE) 1 cells in disease progression (reviewed in Refs. 1 and 2). It has become evident that NE cells are a normal component of both the developing and mature prostatic epithelium and are postulated to be derived from stem cells common to both the exocrine and basal cell populations (3, 4). NE cells produce a variety of neurosecretory products that exhibit growth-promoting activities, including parathyroid hormone-related peptides, neurotensin, serotonin, calcitonin, and bombesin-related peptides (5-9), suggesting that these cells function through endocrine/paracrine mechanisms to regulate the normal development and secretory activity of the prostate.Virtually all prostatic adenocarcinomas contain foci of cells with NE characteristics (10). The presence of extensive multifocal NE features in tumors is an indication of increased aggressiveness and androgen independence (11-13). While the prognostic value of tumor NE status remains controversial, a strong link between NE status and long term, disease-specific survival has been reported (14). Tumor cell populations become enriched for NE cells following long term anti-androgen therapy (15), and although the NE cells appear to be nonmitotic, the carcinoma cells adjacent to these NE foci have been noted to exhibit increased proliferative activity (16, 17). These studies suggest that NE cells that develop within prostate tumors may produce neurosecretory factors that contribute to increased malignancy and decreased responsiveness to androgen ablation therapy.The androgen-responsive prostate tumor cell line, LNCaP, has emerged as a useful model for testing the development of a NE phenotype in adenocarcinoma ...

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“…1 In vertebrates, the autonomic P2X receptors/ channels of the purinergic nervous system constitute a newly-described class of fast response, ligand-gated, calcium-permeable and cation-selective ion channels activated by extracellular ATP from nerve terminals or a local tissue source. 2 The P2X receptors are widelydistributed in mammalian tissues.…”

Section: Introductionmentioning

confidence: 99%

Detection of preneoplasia in histologically normal prostate biopsies

Slater

Delprado

Murphy

et al. 2001

Prostate Cancer Prostatic Dis

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P2X immunolabeling of prostate detected preneoplastic changes in apparently normal tissue. Labeling occurred in two well-de®ned stages before the diagnostic histological markers of cancer were visible. As cancer progressed, the location of P2X expression changed from con®nement within individual nuclei in the acini (stage 1) to a cytoplasmic punctate label in the acinal epithelium, with an associated removal of nuclear stain (stage 2). Finally, in advanced cases, where clear morphological evidence of cancer was apparent, the P2X label condensed exclusively on the apical epithelium (stage 3). BPH/normal tissue was entirely devoid of P2X label. Biopsy samples (77) were tested in three categories. One group (35) were diagnosed as normal benign prostatic hyperplasia (BPH) on the basis of haematoxylin and eosin (H&E) stain, although underlying disease was suspected. Of these, 14 (40%) were clearly normal and appeared entirely devoid of label, 13 (37%) exhibited the ®rst stage of P2X receptor labeling and the remaining eight (23%) exhibited second stage labeling. The accompanying H&E-stained sections of all these cases had a normal appearance. Low grade cancer biopsy samples with Gleason scores G4 ± 7 (25) all revealed widespread second stage receptor labeling in areas of both normal and cancerous morphology, while 17 high grade cancer biopsy samples (Gleason G8 ± 10) all showed third stage labeling along with some residual second stage labeling. The features of each P2X labeling stage occupied the entire histological area affected, offering more opportunity to diagnose the tissue than was supplied by the more-localised diagnostic features identi®ed by H&E-stain. Besides detecting cases of preneoplasia in biopsies with a normal H&E appearance, this technique was also able to rule out the presence of neoplasia in purely hyperplasic prostates by the absence of any P2X labeling. Prostate Cancer and Prostatic Diseases (2001) 4, 92±96.

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Prostate innervation

Cited by 111 publications

References 24 publications

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Nerve growth factor signaling following unilateral pelvic ganglionectomy in the rat ventral prostate is age dependent

Activated 3′,5′-Cyclic AMP-dependent Protein Kinase Is Sufficient to Induce Neuroendocrine-like Differentiation of the LNCaP Prostate Tumor Cell Line

Detection of preneoplasia in histologically normal prostate biopsies

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