Effect of electroacupuncture on the kisspeptin system in a pubertal rat model of polycystic ovary syndrome

Abstract

Objective: To explore the effects and mechanism of action of electroacupuncture (EA) in a rat model of pubertal polycystic ovary syndrome (PCOS). Methods: Female offspring of Sprague-Dawley rats receiving dihydrotestosterone (DHT) during pregnancy (days 16–19), as a model of prenatal androgenization, were divided randomly into three groups: model group (M), EA group, and sham acupuncture (SA) group (n = 8 each). A normal (N) group comprising female offspring of healthy pregnant rats not receiving DHT (n = 8) was added. EA was administered at CV6 and bilateral SP6/ST36 with 2 Hz frequency and 2 mA intensity. SA consisted of superficial needling at different locations without electrical stimulation. Results: EA improved the disturbed estrous cycles, while it could not be concluded that SA was effective in this respect. EA improved ovarian morphology including the number of corpora lutea and area of the ovary, whereas SA did not. However, both EA and SA attenuated the increased luteinizing hormone and decreased estradiol and gonadotropin-releasing hormone levels in the serum of PCOS model rats. Levels of testosterone, follicle-stimulating hormone, and progesterone did not significantly differ between groups. EA and SA alleviated the upregulation of kisspeptin protein and mRNA levels in the hypothalamus and kisspeptin protein level in the arcuate nucleus (ARC). No differences were found between groups in protein or mRNA expression of dynorphin (DYN) or neurokinin B (NKB) in the hypothalamus. Co-expression of kisspeptin, NKB, and DYN were observed in ARC. The GnRH level in the median eminence decreased and could be rescued by EA and SA. Intriguingly, kisspeptin levels in the granulosa cells of the ovary decreased in the model group and could be rescued by EA but not SA. Levels of kisspeptin, NKB, and DYN protein and mRNA in the ovary did not differ between any groups. Conclusion: Both EA and SA appeared to improve symptoms of PCOS at puberty by modulating the kisspeptin system in the hypothalamus. EA also had an effect on ovarian kisspeptin expression and a more comprehensive effect with respect to improving PCOS at puberty than SA.

Effects of electroacupuncture on the expression of hypothalamic neuropeptide Y and ghrelin in pubertal rats with polycystic ovary syndrome

“…However, protein and mRNA expression of GHRL in the hypothalamus and ARC was decreased, and NPY mRNA levels was increased in the pubertal PCOS rats, indicating that NPY and GHRL in hypothalamus are involved in the occurrence of pubertal rats with PCOS. Although the specific mechanism is unclear, we speculate that NPY and GHRL in hypothalamus may participate in development of pubertal PCOS through kisspeptin / GnRH system in view of our previous study showed that the increased expression and release of kisspeptin and GnRH in hypothalamus are the key pathogenesis of pubertal PCOS [7]. The following provides evidence for our conjecture: a, Immunofluorescence doublelabeling experiment showed that GnRH neurons and kisspeptin neurons in ARC were the direct targets of NPY and GHRL in hypothalamus respectively, consistent with research of Conde et al [24] and Dhillon et al [25]; b, Kisspeptin, as the nodal regulatory centre of reproductive function, binds into kisspeptin receptor (G-protein coupled receptor-54, GPR-54) on GnRH neurons or NPY neurons and promotes GnRH and NPY secretion from hypothalamus [26][27][28][29]; c, Previous studies have shown that NPY is necessary for the pulsatility of GnRH release [30], promoting the secretion of GnRH [10].…”

“…Girls treated with GnRH analog drugs (GNRHa) have a significantly increased risk of PCOS during adolescence [6]. Pubertal rats with PCOS showed neuroendocrine dysfunction, characterized by hypersecretion of LH and kisspeptin and elevated release of GnRH from hypothalamus [7]. This elevated hypothalamic GnRH output is likely to stem in part from changed of the metabolic state of the body.…”

Effects of electroacupuncture on the expression of hypothalamic neuropeptide Y and ghrelin in pubertal rats with polycystic ovary syndrome

“…In our previous work, we have revealed that EA at sanyinjiao (SP6), zusanli (ST36), and qihai (CV6) all can improve the disturbed estrous cycles and ovarian polycystic morphological changes of PCOS rats [ 8 ] ( Table 1 , Fig 2 ). Therefore, the bilateral acupoints SP6, ST36 and CV6 were chosen in the EA group.…”

“…Acupoint location refers to “A new attempt of re-mapping acupoint atlas in the rat” by Xu et al [ 26 ]. The methods for EA and SA treatment refer to the previous research [ 8 ]. The details are as follows: Disposable, sterilized, stainless steel needles (Size: 0.16 x 25 mm; lot no.…”

“…Girls treated with GnRH analog drugs (GNRHa) have a significantly increased risk of PCOS during adolescence [ 7 ]. Pubertal rats with PCOS showed neuroendocrine dysfunction, characterized by hypersecretion of LH and kisspeptin and elevated release of GnRH from hypothalamus [ 8 ]. Therefore, abnormalities of the kisspeptin/GnRH system may be fundamental contributors to the mechanism of pubertal PCOS.…”