Abstract
BackgroundEstradiol 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.MethodsIn 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).ResultsIt 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.ConclusionThe 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.
Highlights
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder recognized as the primary cause of infertility in women of the reproductive age [1]
We have recently demonstrated that repeated low-frequency EA treatments induced regular ovulations in more than onethird of the women affected by PCOS and normalized endocrine and neuroendocrine parameters without any negative side-effects [17]
Using the steroid-induced polycystic ovaries (PCO) model, we found that repeated treatments of low-frequency EA in somatic segment related to the innervation of the ovary, reduced high concentrations of ovarian nerve growth factor (NGF), corticotrophin-releasing factor (CRF), and endothelin-1 as well as increased low concentrations of hypothalamic β-endorphin [18,19,20,21]
Summary
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder recognized as the primary cause of infertility in women of the reproductive age [1]. The EV-induced rat PCO model reflects some endocrinological and morphological characteristics of human PCOS, and it is assumed that activity in the ovarian sympathetic nerves is higher than in normal rats [8,9,10]. This is evidenced by an early increase in ovarian levels of norepinephrine (NE), an enhanced release of NE from ovarian nerve terminals, an increased activity of the catecholamine synthesis-limiting enzyme tyrosine hydroxylase (TH), and down-regulation of β2-adrenoceptors (ARs) in theca-interstitial cells [8,9,10]. 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
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