Changes in sympathetic nerve activity of the mammalian ovary during a normal estrous cycle and in polycystic ovary syndrome: Studies on norepinephrine release

Lara, Hernán E.; Dorfman, Mauricio D.; Venegas, Mauricio; Luza, Sandra; Luna, Selva L.; Mayerhofer, Artur; Guimarães, Marta Brito; Silva, A.A.M. Rosa E; Ramírez, Victor D.

doi:10.1002/jemt.10229

Cited by 116 publications

(121 citation statements)

References 36 publications

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“…The downregulation of ovarian ␣ 2 -AR mRNA in PCO rats has been reported previously (21,22), as has ␤ 2 -AR hyperresponsiveness to challenges by ␤ 2 agonists (5). It is also worth mentioning that the activity of the sympathetic nervous system and the ovarian NE content regulate the expression of ␤ 2 -AR after the induction of PCO (22).…”

Section: Discussionsupporting

confidence: 57%

Effect of anti-NGF on ovarian expression of α₁- and β₂-adrenoceptors, TrkA, p75^NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries

Manni¹,

Holmäng²,

Cajander³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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(PCO) in rats are associated with higher ovarian release and content of norepinephrine, decreased ␤2-adrenoceptors (ARs), and dysregulated expression of ␣1-AR subtypes, all preceded by an increase in the production of ovarian NGF. The aim of this study was to further elucidate the role of NGF in the ovaries by blocking the action of NGF during development of EV-induced PCO in rats. Control and EV-injected rats were treated with intraperitoneal injections of IgG (control and PCO groups) or with anti-NGF antibodies (anti-NGF and PCO anti-NGF groups) every third day for 5 wk starting from the day of PCO induction. Rat weight, estrous cyclicity, ovarian morphology, ovarian mRNA, and protein expression of ␣1-AR subtypes, ␤2-AR, the NGF receptor tyrosine kinase A (TrkA), p75 neurotrophin receptor (p75 NTR ), and tyrosine hydroxylase (TH) were analyzed. Ovaries in both PCO and PCO anti-NGF groups decreased in size as well as in number and size of corpora lutea. mRNA expression of ␣ 1a-AR and TrkA in the ovaries was lower, whereas expression of ␣ 1b-and ␣1d-AR and TH was higher, in the PCO group than in controls. Protein quantities of ␣ 1-ARs, TrkA, p75 NTR , and TH were higher in the PCO group compared with controls, whereas the protein content of ␤ 2-AR was lower. Anti-NGF treatment in the PCO group restored all changes in mRNA and protein content, except that of ␣ 1b-AR and TrkA mRNAs, to control levels. The results indicate that the NGF/NGF receptor system plays a role in the pathogenesis of EV-induced PCO in rats.nerve growth factors; sympathetic nervous system; ovarian innervation; tyrosine kinase A; p75 neutrophin receptor POLYCYSTIC OVARY SYNDROME (PCOS) is a heterogeneous condition of uncertain etiology that affects between 5% and 10% of women of reproductive age (41). PCOS is characterized by a myriad of symptoms and signs, which include ovulatory dysfunction, the presence of polycystic ovaries (PCO), abdominal obesity, hyperandrogenism, and in many cases hypertension and insulin resistance (41). Several theories have been proposed to explain the pathogenesis of PCOS, such as an enhanced production of ovarian androgens, an alteration in the metabolism of cortisol resulting in enhanced production of adrenal androgens, a defect in the action and secretion of insulin, and a neuroendocrine defect that causes an exaggeration in the pulse and frequency amplitude of LH (41).The involvement of the sympathetic nervous system in the etiology and maintenance of PCOS is suggested by both clinical and experimental findings (5,20,22,24,25). Ovarian function is known to be regulated by both hormonal and intraovarian signaling. It is also known that the sympathetic innervation of the ovary is involved in follicular development (23) and in ovarian steroidogenesis (1). That the sympathetic nervous system is involved in the pathophysiology of human PCOS is supported by the fact that the innervation of the catecholaminergic nerve fibers in the PCO of women with PCOS is more dense than in normal ovaries (18,35).Chronic anovulati...

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Section: Discussionsupporting

confidence: 57%

Effect of anti-NGF on ovarian expression of α₁- and β₂-adrenoceptors, TrkA, p75^NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries

Manni¹,

Holmäng²,

Cajander³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…As discussed previously, there is also an increase in the adrenergic tone of the ovary in the model that uses oestradiol valerate administration (Lara et al 1993). In this model, it is possible to observe the same changes in follicular dynamics that are seen in the ovaries of ageing rats (Lara et al 2002, Acuna et al 2009, Cruz et al 2012. Within these changes, we observe a decrease in preantral and antral follicles, a decrease (or absence) of corpora lutea and the appearance of type III and cystic follicles.…”

Section: R64mentioning

confidence: 82%

“…Both α and β adrenergic receptors are expressed in the ovarian follicles (Aguado et al 1982, Barria et al 1993, Itoh & Ishizuka 2005, Fernandois et al 2012, and direct effects of NE on follicles could be produced by α1 and β2 adrenergic receptor stimulation (Laszlovszky & Erdo 1983, Itoh & Ishizuka 2005. Interestingly, both sympathetic activity and the density of β receptors in the ovary change with the oestrous cycle in the rat (Lara et al 2002). Regarding follicular development, the surgical section of the ovarian superior nerve (SON) in pigs increases the number of small follicles (<3 mm) and decreases the number of large follicles (>7 mm).…”

Section: Sympathetic Innervation and Ovarian Ageingmentioning

confidence: 99%

Ovarian function and reproductive senescence in the rat: role of ovarian sympathetic innervation

2017

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Successful reproduction is the result of a myriad interactions in which the ovary and the ovarian follicular reserve play a fundamental role. At present, women who delay maternity until after 30 years of age have a decreased fertility rate due to various causes, including damaged follicles and a reduction in the reserve pool of follicles. Therefore, the period just prior to menopause, also known as the subfertile period, is important. The possibility of modulating the follicular pool and the health of follicles during this period to improve fertility is worth exploring. We have developed an animal model to study the ovarian ageing process during this subfertile period to understand the mechanisms responsible for reproductive senescence. In the rat model, we have shown that the sympathetic nervous system participates in regulating the follicular development during ovarian ageing. This article reviews the existing evidence on the presence and functional role of sympathetic nerve activity in regulating the follicular development during ovarian ageing, with a focus on the subfertile period. Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/153/2/ R59/suppl/DC1. Reproduction (2017) 153 R59-R68

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“…Ovarian norepinephrine levels are substantially higher than those in circulating blood (36,37), and SNS activity can further enhance those levels to induce precystic follicles (38,39). The doses of norepinephrine used for our study were selected to reflect the physiologic conditions of this hormone at the level of the tissue microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis

Sood¹,

et al. 2010

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Chronic stress is associated with hormonal changes that are known to affect multiple systems, including the immune and endocrine systems, but the effects of stress on cancer growth and progression are not fully understood. Here, we demonstrate that human ovarian cancer cells exposed to either norepinephrine or epinephrine exhibit lower levels of anoikis, the process by which cells enter apoptosis when separated from ECM and neighboring cells. In an orthotopic mouse model of human ovarian cancer, restraint stress and the associated increases in norepinephrine and epinephrine protected the tumor cells from anoikis and promoted their growth by activating focal adhesion kinase (FAK). These effects involved phosphorylation of FAK Y397 , which was itself associated with actin-dependent Src interaction with membrane-associated FAK. Importantly, in human ovarian cancer patients, behavioral states related to greater adrenergic activity were associated with higher levels of pFAK Y397 , which was in turn linked to substantially accelerated mortality. These data suggest that FAK modulation by stress hormones, especially norepinephrine and epinephrine, can contribute to tumor progression in patients with ovarian cancer and may point to potential new therapeutic targets for cancer management.

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Changes in sympathetic nerve activity of the mammalian ovary during a normal estrous cycle and in polycystic ovary syndrome: Studies on norepinephrine release

Cited by 116 publications

References 36 publications

Effect of anti-NGF on ovarian expression of α₁- and β₂-adrenoceptors, TrkA, p75^NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries

Effect of anti-NGF on ovarian expression of α₁- and β₂-adrenoceptors, TrkA, p75^NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries

Ovarian function and reproductive senescence in the rat: role of ovarian sympathetic innervation

Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis

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Changes in sympathetic nerve activity of the mammalian ovary during a normal estrous cycle and in polycystic ovary syndrome: Studies on norepinephrine release

Cited by 116 publications

References 36 publications

Effect of anti-NGF on ovarian expression of α1- and β2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries

Effect of anti-NGF on ovarian expression of α1- and β2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries

Ovarian function and reproductive senescence in the rat: role of ovarian sympathetic innervation

Adrenergic modulation of focal adhesion kinase protects human ovarian cancer cells from anoikis

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Product

Resources

About

Effect of anti-NGF on ovarian expression of α₁- and β₂-adrenoceptors, TrkA, p75^NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries

Effect of anti-NGF on ovarian expression of α₁- and β₂-adrenoceptors, TrkA, p75^NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries