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      Effect of electro-acupuncture on ovarian expression of α (1)- and β (2)-adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries

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          Abstract

          Background

          Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz) electro-acupuncture (EA) has been shown to modulate sympathetic markers as well as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in rats with EV-induced PCO.

          Methods

          In the present study, we further tested the hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow in rats with PCO, induced by a single i.m. injection of EV, by investigating the mRNA expression, the amount and distribution of proteins of α1a-, α1b-, α1d-, and β2-adrenoceptors (ARs), as well as the low-affinity neurotrophin receptor (p75NTR).

          Results

          It was found that EV injection results in significantly higher mRNA expression of ovarian α1b- and α1d-AR in PCO rats compared to control rats. The p75NTR and β2-ARs mRNA expression were unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower expression of β2-ARs mRNA expression in PCO rats. The p75NTR mRNA was unaffected in both PCO and control rats. PCO ovaries displayed significantly higher amount of protein of α1a-, α1b- and α1d-ARs, and of p75NTR, compared to control rats, that were all counteracted by repeated low-frequency EA treatments, except for α1b-AR.

          Conclusion

          The present study shows that EA normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was able to prevent the EV-induced up regulation of p75NTR, probably by normalizing the sympathetic ovarian response to NGF action. Our data indicate a possible role of EA in the regulation of ovarian responsiveness to sympathetic inputs and depict a possible complementary therapeutic approach to overcoming sympathetic-related anovulation in women with PCOS.

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          Most cited references31

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          Alpha-adrenoceptor subtypes.

          Different studies have led to our present knowledge of the membrane receptors responsible for mediating the responses to the endogenous catecholamines. These receptors were initially differentiated into alpha - and beta-adrenoceptors. Alpha-adrenoceptors mediate most excitatory functions, and were in turn differentiated in the 1970s into alpha(1)- and alpha(2)-adrenoceptors. The alpha(1)-adrenoceptor type usually mediates responses in the effector organ. The alpha(2)-adrenoceptor type is located presynaptically and regulates the release of the neurotransmitter but it is also present in postsynaptical locations. Both alpha-adrenoceptors are important for the control of vascular tone, but we now know that neither alpha(1)- nor alpha(2)-adrenoceptors constitute homogeneous groups. Each alpha-adrenoceptor type can be subdivided into different subtypes and in this review we have turned our attention to these. The alpha(1)- and the alpha(2)-adrenoceptor subtypes were previously defined pharmacologically by functional and binding studies, and later they were also isolated and identified using cloning methods. In fact, the study of alpha-adrenoceptors was revolutionized by the techniques of molecular biology which permitted us to establish the present classification. The present classification of alpha(1)-adrenoceptors stands as follows: alpha(1A)-adrenoceptor subtype (cloned alpha(1c) and redesignated alpha(1a/c)), alpha(1B)-adrenoceptor subtype (cloned alpha(1b)) and alpha(1D)-adrenoceptor subtype (cloned alpha(1d) and redesignated alpha(1a/d)). It has not been easy to establish the distribution of these alpha(1)-adrenoceptor subtypes in the various organs and tissues, or to define the functional response mediated by each one in the different species studied. Nevertheless it seems that the alpha(1A)-adrenoceptor subtype is more implicated in the maintenance of vascular basal tone and of arterial blood pressure in conscious animals, and the alpha(1B)-adrenoceptor subtype participates more in responses to exogenous agonists. It has also been observed that the expression of the alpha(1B)-adrenoceptor subtype can be modified in pathological situations and particular attention has been paid to the regulation of expression of this receptor. The present classification of alpha(2)-adrenoceptors stands as follows: alpha(2A/D)-adrenoceptor subtype (today it is accepted that the alpha(2A)-adrenoceptor subtype and the alpha(2D)-adrenoceptor subtype are the same receptor but they were identified in different species: the alpha(2A) in human and the alpha(2D) in rat); alpha(2B)-adrenoceptor subtype (cloned alpha(2b)) and alpha(2C)-adrenoceptor subtype (cloned alpha(2c)). Today we know that the alpha(2A/D)- and alpha(2B)-adrenoceptor subtypes in particular control arterial contraction, and that the alpha(2C)-adrenoceptor subtype is responsible above all for venous vasoconstriction. We also know that the alpha(2 A/D)-adrenoceptor subtype fundamentally mediates the central effects of the alpha(2)-adrenoceptor agonists. Despite the validity of the above-mentioned classification of the alpha(1)- and alpha(2)-adrenoceptors, it seems clear that the contractions of a large number of tissues including smooth muscle are mediated by more than one alpha-adrenoceptor subtype. Moreover, few ligands recognise only one alpha-adrenoceptor subtype and the lack of specifity in the different drugs for each one limits their administration in vivo and their therapeutic use. Copyright 2001 Academic Press.
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            Development of the polycystic ovarian condition (PCO) in the estradiol valerate-treated rat.

            A wide range of experimental manipulations results in an anovulatory polycystic ovarian (PCO) condition in the rat. Although PCO has been studied in a number of these models, research has centered on the condition after it is well established rather than as it develops. Consequently, it is still not clear exactly what follicular cysts are or how and why they form. Therefore, we studied the development of PCO in rats treated with estradiol-valerate (EV). In this model, definitive cysts were present 8-9 wk after a single injection of EV. Animals were killed at 5, 11, 16, 21, 28 and 56 days after EV treatment. Serum was assayed for luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Ovaries were weighed and prepared for histologic examination. The ovaries were serially sectioned such that the number and size distribution of normal and atretic follicles could be assessed quantitatively. Oviducts were examined for the presence of ova. Immediately after EV treatment, ovulatory cycles ceased; by 16-20 days posttreatment, all animals exhibited persistent vaginal cornification. Basal concentrations of serum LH and FSH fell to a nadir at 11 days posttreatment, after which both gonadotropins exhibited a trend toward recovery. Within the first 28 days after treatment, ovarian weights declined significantly as did the total number of healthy follicles. Atretic follicles of all sizes were particularly numerous at 16 days. By 28 days, the decline in the number of healthy follicles reached a plateau. Numerous atretic, large secondary follicles were particularly prominent on the background of the decreasing number of normal follicles.(ABSTRACT TRUNCATED AT 250 WORDS)
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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.

              Although it has been known for many years that the ovary is innervated by catecholaminergic nerve fibers and much experimental evidence has strengthened the notion that catecholamines are physiologically involved in the control of ovarian function, scarce evidence has been presented as to the role of sympathetic activity in ovarian pathologies that affect reproductive function. The purpose of this article is to provide a succinct overview of the findings in this area and discuss them relative to the pathology of polycystic ovary syndrome, the most common ovarian pathology in women during their reproductive years. Copyright 2002 Wiley-Liss, Inc.
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                Author and article information

                Journal
                Reprod Biol Endocrinol
                Reproductive biology and endocrinology : RB&E
                BioMed Central (London )
                1477-7827
                2005
                7 June 2005
                : 3
                : 21
                Affiliations
                [1 ]Cardiovascular Institute and Wallenberg Laboratory, Sahlgrenska Academy, Göteborg University, SE-413 45 Göteborg, Sweden
                [2 ]Institute of Neurobiology and Molecular Medicine (CNR), Rome, Italy
                [3 ]Rehabilitation Medicine, Karolinska Hospital, SE-171 77 Stockholm, Sweden
                [4 ]Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital, Sahlgrenska, SE-413 45 Göteborg, Sweden
                [5 ]Institute of Occupational Therapy and Physical Therapy, Sahlgrenska Academy, Göteborg University, SE-405 30 Göteborg, Sweden
                Article
                1477-7827-3-21
                10.1186/1477-7827-3-21
                1175857
                15941472
                105e6ca7-a97e-4465-92a7-3c41ecda50ce
                Copyright © 2005 Manni et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 May 2005
                : 7 June 2005
                Categories
                Research

                Human biology
                Human biology

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