Vasoactive intestinal peptide modulates steroid hormone secretion via the superior ovarian nerve in a rat model of polycystic ovary syndrome

Q3 Medicine
Gabriela Rosas Gavilán , Rosa Linares Culebro , Elizabeth Vieyra Valdez , Deyra A. Ramírez Hernández , Julieta A. Espinoza Moreno , Andrea Chaparro Ortega , Roberto Domínguez Casalá , Leticia Morales-Ledesma
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Abstract

Ovarian steroidogenesis is an essential process that modulates reproduction. In the cyclic rat, vasoactive intestinal peptide (VIP) stimulates the secretion of steroid hormones, and this is dependent on the superior ovarian nerve (SON). In a rat model of polycystic ovarian syndrome induced by an estradiol valerate injection (PCOS-EV), the increase in SON activity results in elevated levels of norepinephrine (NE) and VIP in the ovary, which in turn leads to a rise in androgen. To analyze whether a greater influx of NE to the ovary, due to the hyperactivity of the SON, modifies the response of the gonad to VIP, PCOS-EV or vehicle-treated rats (Vh) were subjected to: 1) stimulation of the left or right ovary with VIP (L-VIP or R-VIP), or 2) the left or right section of the SON (LSON or RSON) followed by injection of VIP into the denervated ovary. Animals were euthanized 1 h later, and the serum levels of steroid hormones were assessed. In Vh rats treated on estrus, VIP stimulation increased the serum levels of testosterone, irrespective of the ovary injected (Vh L-VIP: 17.3 ± 0.5 or Vh R-VIP: 11.3 ± 1.1 vs. Vh: 6.4 ± 1.3). Section of the SON prior to VIP stimulation did not modify testosterone secretion (Vh LSNO+L-VIP: 15.5 ± 2.7 vs. Vh L-VIP: 17.3 ± 0.5; Vh RSNO+R-VIP: 10.6 ± 0.9 vs. Vh R-VIP: 11.3 ± 1.1). In PCOS-EV rats, VIP stimulation of the left ovary lowered testosterone (EV L-VIP: 11.0 ± 4.0 vs. EV: 24.6 ± 2.5). On the other hand, the effects of VIP injection into the denervated ovary were asymmetric, i.e., treatment in the left ovary not modified testosterone levels (EV LSNO+L-VIP: 6.3 ± 1.3 vs. EV L-VIP: 11.0 ± 4.0), while it decreased testosterone when performed in the right ovary (EV RSNO+R-VIP: 6.9 ± 1.3 vs. EV R-VIP: 29.6 ± 7.6). These results show that, in estrus, VIP has a stimulating effect on testosterone secretion, which is amplified by SON signals. Contrary to this, in the PCOS-EV rat, VIP lowers the elevated levels of androgens that characterize this animal model. Based on present results, we suggest that VIP could be used as a treatment for PCOS.

在多囊卵巢综合征大鼠模型中,血管活性肠肽通过卵巢上神经调节类固醇激素的分泌
卵巢类固醇生成是调节生殖的重要过程。在周期性大鼠体内,血管活性肠肽(VIP)刺激类固醇激素的分泌,而这依赖于卵巢上神经(SON)。在通过注射戊酸雌二醇诱导的多囊卵巢综合症大鼠模型(PCOS-EV)中,SON 活性的增加导致卵巢中去甲肾上腺素(NE)和 VIP 水平升高,进而导致雄激素上升。为了分析由于 SON 活性亢进而导致更多 NE 流入卵巢是否会改变性腺对 VIP 的反应,我们对 PCOS-EV 或用药物治疗的大鼠(Vh)进行了以下实验:1) 用 VIP 刺激左侧或右侧卵巢(L-VIP 或 R-VIP),或 2) 切断 SON 左侧或右侧部分(LSON 或 RSON),然后向去神经支配的卵巢注射 VIP。动物在 1 小时后安乐死,并对血清中的类固醇激素水平进行评估。在发情期接受治疗的 Vh 大鼠中,无论注射哪种卵巢,VIP 刺激都会增加血清中的睾酮水平(Vh L-VIP: 17.3 ± 0.5 或 Vh R-VIP: 11.3 ± 1.1 vs. Vh: 6.4 ± 1.3)。在进行 VIP 刺激之前切除 SON 不会改变睾酮的分泌(Vh LSNO+L-VIP: 15.5 ± 2.7 vs. Vh L-VIP: 17.3 ± 0.5; Vh RSNO+R-VIP: 10.6 ± 0.9 vs. Vh R-VIP: 11.3 ± 1.1)。在 PCOS-EV 大鼠中,VIP 对左侧卵巢的刺激降低了睾酮(EV L-VIP:11.0 ± 4.0 vs. EV:24.6 ± 2.5)。另一方面,向去神经支配的卵巢注射 VIP 的影响是不对称的,即在左侧卵巢进行治疗不会改变睾酮水平(EV LSNO+L-VIP: 6.3 ± 1.3 vs. EV L-VIP: 11.0 ± 4.0),而在右侧卵巢进行治疗则会降低睾酮水平(EV RSNO+R-VIP: 6.9 ± 1.3 vs. EV R-VIP: 29.6 ± 7.6)。这些结果表明,在发情期,VIP 对睾酮分泌有刺激作用,而这种作用会被 SON 信号放大。与此相反,在 PCOS-EV 大鼠中,VIP 可降低该动物模型特有的雄激素水平升高。根据目前的研究结果,我们认为 VIP 可用于治疗多囊卵巢综合症。
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来源期刊
Endocrine and Metabolic Science
Endocrine and Metabolic Science Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.80
自引率
0.00%
发文量
4
审稿时长
84 days
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