The role of kisspeptin/neurokinin B/dynorphin neurons in pathomechanism of vasomotor symptoms in postmenopausal women: from physiology to potential therapeutic applications. (2nd November 2018)

• Record Type: Journal Article
• Authors: Szeliga, Anna; Czyzyk, Adam; Podfigurna, Agnieszka; Genazzani, Andrea R.; Genazzani, Alessandro D.; Meczekalski, Blazej
• Is Part Of: Gynecological endocrinology. Volume 34:Number 11(2018)
• Page Start: 913
• Page End: 919
• Publication Date: 2018-11-02
• Subjects: Neurokinin B -- vasomotor symptoms -- kisspeptin -- KNDy -- menopause; Endocrine gynecology -- Periodicals; Generative organs, Female -- Diseases -- Periodicals; 618.1
• DOI: 10.1080/09513590.2018.1480711
• Languages: English
• ISSNs: 0951-3590

Abstract

Abstract: Women during perimenopausal period experience a range of symptoms, which interfere with physical, sexual, and social life. About 65–75% of symptoms connected with postmenopausal period are vasomotor symptoms (VMS), such as hot flushes and night sweats. Hot flushes are subjective sensation of heat associated with cutaneous vasodilatation and drop in core temperature. It is suspected that VMS are strongly correlated with pulsatile oversecretion of gonadotropin-releasing hormone (GnRH) and subsequently luteinizing hormone (LH). Evidence has accumulated in parallel showing that lack of negative feedback of steroid hormones synthesized in ovary causes overactivation of hypertrophied kisspeptin/neurokinin B/dynorphin (KNDy) neurons, located in infundibular nucleus. Oversecretion of both kisspeptin (KISS1) and neurokinin B (NKB), as well as downregulation of dynorphin, plays dominant role in creation of GnRH pulses. This in turn causes VMS. Administration of senktide, highly potent and selective NK3R agonist, resulted in increase of serum LH concentration, induction of VMS, increase in heart rate, and skin temperature in postmenopausal women. These finding suggest that modulation of KNDy neurons may become new therapeutic approach in the treatment of VMS. 摘要: 围绝经期的妇女会出现一系列症状, 这些症状会干扰身体, 性生活和社交。绝经期间约65-75％的症状是血管舒缩症状（VMS）, 如潮热和盗汗。潮热是与皮肤血管舒张和核心温度下降相关的主观热感。VMS被怀疑与促性腺激素释放激素（GnRH）脉冲式释放过多和随后的黄体生成素（LH）分泌密切相关。同时研究显示, 卵巢中合成的类固醇激素缺乏负反馈导致位于漏斗核中的肥大Kisspeptin /神经激肽B /强啡肽（KNDy）神经元过度活化。 Kisspeptin（KISS1）和神经激肽B（NKB）的过度分泌以及强啡肽的下调在GnRH脉冲的产生中起主导作用, 反之导致VMS的发生。给予NK3受体特异性激动剂, 高效选择性NK3R激动剂导致绝经后妇女血清LH浓度增加, 诱导VMS发生, 心率增加和皮肤温度升高。这些发现表明, 对KNDy神经元的调节可能成为治疗VMS的新方法。