Estrogen selectively increases sensory nociceptor innervation of arterioles in the female rat

Blacklock, Audrey D.; Cauveren, Jamie A; Smith, Peter G.

doi:10.1016/j.brainres.2004.05.075

Cited by 30 publications

(29 citation statements)

References 64 publications

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“…None of the steroids had any effect on neurite initiation. This is similar to the previously reported action of estradiol on neurite growth in adult nociceptor neurons (Blacklock et al, 2004) and androgen actions on PC12 cells transfected with AR (Lustig et al, 1994) or immortalised motoneurons (Marron et al, 2005). However, it is quite different from the actions of neurotrophic factors on pelvic autonomic neurons, where nerve growth factor (Meusburger and Keast, 2001) and neurturin (Wanigasekara and Keast, 2005) stimulated both neurite initiation and increased neurite complexity (length, branching and primary neurites) in sympathetic and parasympathetic pelvic neurons, respectively.…”

Section: Discussionsupporting

confidence: 70%

Androgen and estrogen receptor–mediated mechanisms of testosterone action in male rat pelvic autonomic ganglia

et al. 2007

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Although male reproductive function is primarily androgen dependent, many studies suggest that estrogens have direct actions on the male reproductive organs. Pelvic autonomic neurons provide the motor control of the internal reproductive organs and the penis and various properties of these neurons are affected by endogenous androgens. However, the possible role of estrogens at this site has not been examined. Here we have investigated the significance of estrogens produced by aromatisation of testosterone in the physiological actions of androgens on adult male rat pelvic ganglion neurons. RT-PCR studies showed that aromatase and both estrogen receptors (ERα and ERβ) are expressed in these ganglia. Western blotting also showed that aromatase is expressed in male pelvic ganglia. Using immunohistochemical visualisation, ERα was predominantly expressed by nitric oxide synthase (NOS)-positive parasympathetic pelvic ganglion neurons. In vivo studies showed that the decrease in pelvic ganglion soma size caused by gonadectomy could be prevented by administration of testosterone (T) or dihydrotestosterone (DHT), but not 17β-estradiol (E2), showing that this maintenance action of testosterone is mediated entirely by androgenic mechanisms. However, in vitro studies of cultured pelvic ganglion neurons revealed that T, DHT and E each stimulated the growth of longer and more complex neurites in both noradrenergic and cholinergic NOS-expressing neurons. The effects of T were attenuated by either androgen or estrogen receptor antagonists, or by inhibition of aromatase. Together these studies demonstrate that estrogens are likely to be synthesised in the male pelvic ganglia, produced from testosterone by local aromatase. The effects of androgens on axonal growth are likely to be at least partly mediated by estrogenic mechanisms, which may be important for understanding disease-, aging-and injury-induced plasticity in this part of the nervous system. KeywordsSteroid; autonomic ganglion; urogenital; regeneration Recent studies suggest that within the framework of androgen dependence of male reproductive function, endogenous estrogens produced by aromatisation of testosterone within local tissues Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 August 10. Published in final edited form as:Neuroscience. 2007 August 10; 148(1): 92-104. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript are important for development and function of male reproductive organs. Many of the male re...

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Section: Discussionsupporting

confidence: 70%

Androgen and estrogen receptor–mediated mechanisms of testosterone action in male rat pelvic autonomic ganglia

et al. 2007

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“…However, recent data suggest that the explanation may be more complex. Autonomic and sensory neurons express ERs 11–13 and are responsive to E 2 in culture 14, 15, 16 , supporting the idea that E 2 can act directly on peripheral neurons. In addition, E 2 induces uterine myometrium to produce neuromodulatory factors 17–19 , and may do so in other parts of the reproductive tract.…”

Section: Introductionmentioning

confidence: 71%

Systemic and topical hormone therapies reduce vaginal innervation density in postmenopausal women

Griebling¹,

Liao

Smith

2012

Menopause

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Objective Menopause is often accompanied by vaginal discomfort including burning, itching, dryness and spontaneous or provoked pain. While direct effects of estrogen withdrawal on vaginal cells are implicated, surgical menopause in rodents causes autonomic and sensory nerves to proliferate, suggesting that indirect effects mediated by changes in vaginal innervation may contribute. We assessed whether post-menopausal women display hormone-dependent changes in vaginal innervation. Methods Vaginal biopsies from 20 postmenopausal women undergoing surgery for stress urinary incontinence and pelvic organ prolapse were fixed and immunostained for the pan-neuronal marker, PGP9.5, the sympathetic marker tyrosine hydroxylase, the parasympathetic marker vasoactive intestinal polypeptide, and the sensory nociceptor marker calcitonin gene-related peptide. Innervation density was measured as apparent percentage of section area occupied by immunofluorescent axons. Specimens were grouped according to whether participants received systemic hormone therapy (HT), topical (vaginal) HT, or no HT. Results Women not receiving HT showed relatively high levels of total innervation, with most axons expressing tyrosine hydroxylase or vasoactive intestinal polypeptide immunoreactivity. In patients receiving systemic HT, overall innervation was reduced, as were presumptive parasympathetic, sympathetic and sensory axon populations. Topical HT elicited more dramatic reductions in innervation than systemic HT. Conclusions Hormone therapy reduces autonomic and sensory vaginal innervation density, which may in part contribute to relief from vaginal discomfort. Moreover, topical therapy is more effective than systemic therapy, which may help explain the greater improvement reported with topical as compared to systemic HT.

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“…However, there are sex differences in the mechanisms involved: in hypertensive males both the vasodilator response to CGRP and RAMP1 expression remain unmodified [36], suggesting an increased CGRP release, whereas in females, the effect observed is the result of an increase in vasodilator response mediated by increased RAMP1 expression associated with decreased CGRP release. The role of CGRP in hypertension is modulated by a number of factors including the reninangiotensin system, steroids, hormones, and so on [40,41], depending on the hypertension model. The notorious sex differences described for these factors in hypertension [42,43] could explain the sex differences observed here.…”

Section: Discussionmentioning

confidence: 99%

Hypertension alters the function of nitrergic and sensory innervation in mesenteric arteries from female rats

Campo

Ferrer

Balfagón

2009

Journal of Hypertension

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Estrogen selectively increases sensory nociceptor innervation of arterioles in the female rat

Cited by 30 publications

References 64 publications

Androgen and estrogen receptor–mediated mechanisms of testosterone action in male rat pelvic autonomic ganglia

Androgen and estrogen receptor–mediated mechanisms of testosterone action in male rat pelvic autonomic ganglia

Systemic and topical hormone therapies reduce vaginal innervation density in postmenopausal women

Hypertension alters the function of nitrergic and sensory innervation in mesenteric arteries from female rats

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