雄激素调控麝鼠香囊腺分泌麝鼠香的分子机制研究

Muskrat is one of the major economic animals in China. The scented gland of male muskrat secretes musk, which has similar pharmacological effects as the natural musk. However, how the secretion of musk in the males is regulated is largely unclear. Our previous studies found that morphological and histological changes of the scented gland were positively correlated with serum testosterone concentration, and androgen receptor (AR), P450arom and estrogen receptors (ERα and ERβ) were also highly expressed in glandular cells of the scented gland. Based on these findings, we hypothesize that androgen is a key player during the process of musk secretion. Androgen either binds to its receptor, or being converted into estrogen, which subsequently binds to estrogen receptors to exert its function. Thus, these steroid hormones may regulate the function of the musk gland in an endocrine or autocrine/paracrine manner. The present project herein focuses on the following aspects: 1. clarify the roles of androgen and estrogen in regulating the secretion of musk during the breeding and non-breeding seasons under natural conditions; 2. further verify the functions of androgen and estrogen in the musk secretion in vitro and in vivo, either utilizing cultured scented glandular cells or applying orchiectomy, hormonal interference experiments; 3. identify the key target genes mediating the actions of androgen/estrogen, and the molecular mechanism how androgen and estrogen regulating scented gland of muskrat secrete muskrat musk via in vitro and in vivo model. The prospective outcome of this study will help us to gain basic knowledge in the biology of the musk secretion. The expected data will also lay a solid theoretical foundation for improving the musk production in this species, which may boost the industrialization of muskrat cultivation and musk production.

麝鼠是我国重要的特种经济动物之一，雄性麝鼠香囊腺分泌的麝鼠香，药理作用与天然麝香相似，是天然麝香的重要补充，但香囊腺分泌麝鼠香的调控机制尚不清楚。我们前期研究发现：麝鼠香囊腺形态学和组织学变化与其血清中睾酮浓度变化呈正相关，香囊腺腺细胞表达雄激素受体、雌激素合成酶和雌激素受体。据此推测：雄激素是调节麝鼠分泌麝鼠香的重要因素，雄激素可与其受体结合或转化为雌激素并与其受体结合，调控香囊腺泌香的功能。本项目研究的主要内容包括：1.自然条件下，研究繁殖期和非繁殖期雄激素和雌激素调节麝鼠香囊腺泌香功能作用；2. 通过睾丸摘除，激素干扰和香囊腺腺细胞培养实验，研究雄激素和雌激素调控麝鼠香囊腺泌香功能；3.通过体外和体内实验确定雄激素和雌激素信号通路下游关键基因，阐明雄激素和雌激素调控麝鼠香囊腺泌香的分子机制。项目结果为提高麝鼠香囊腺泌香产量和质量提供基础数据，并服务于麝鼠养殖业和麝鼠香产业化发展需求。

麝鼠是我国重要的特种经济动物之一，每年3-10月时为繁殖期。雄性麝鼠在繁殖期也即泌香期能够分泌麝鼠香。麝鼠香含有麝香酮、多种酯类、脂肪酸类、大环烷酮类及甾体类化合物，具有抗痴呆、抗炎、抗心肌缺血、抗肿瘤等多种作用；麝鼠香中还含有棕榈酸，亚油酸等脂肪酸类成分，具有抗氧化作用、调节血脂、软化血管、降压等活性，具有良好的药用价值。该项目主要研究内容包括：（1）自然条件下，阐明雄激素通过内分泌或自分泌与旁分泌调节麝鼠香囊腺分泌麝鼠香的功能；（2）实验室条件下，通过香囊腺腺细胞体外培养实验，阐明雄激素通过不同途径调控麝鼠香囊腺分泌麝鼠香功能作用；（3）多重组学联合分析筛选麝鼠香囊腺泌香期和非泌香期的差异基因，确定麝鼠麝香酮合成代谢途径。研究结果表明：雄激素、雌激素和催乳素受体以及性类固醇激素合成酶都在麝鼠繁殖期和非繁殖期腺细胞的细胞核中呈现免疫阳性表达，且繁殖期的麝鼠香囊腺细胞表达水平较高；麝鼠繁殖期香囊腺组织雄激素、雌激素和催乳素浓度具有较高水平；转录组学结果表明繁殖期和非繁殖期的香囊腺差异表达基因主要富集在雄激素和雌激素信号通路、脂质代谢过程和维生素D合成等通路上，qRT-PCR结果证实了转录组结果；质谱成像和代谢组学联合分析显示发现香囊腺内磷脂分子PC（32:0）和LysoPC（16:0）代谢途径的季节性变化，解析并证明了香囊腺内脂质成分的代谢途径变化。关键数据表明麝鼠香囊腺是雄激素和雌激素的靶器官，雄激素和雌激素能够通过内分泌、自分泌或旁分泌调控香囊腺的泌香功能，雄激素可以调控麝香酮合成代谢；多组学联合分析和验证揭示了繁殖期与非繁殖期麝鼠香囊腺内代谢途径差异主要集中在脂肪酸代谢。此项研究是麝鼠香囊腺分泌麝鼠香基础研究的重要一环，研究结果不仅可为人工科学饲养麝鼠、提高麝鼠香的产量和质量以及为麝鼠香可持续开发和利用提供科学的参考数据，同时还对我国濒危动物麝鹿的保护具有重要意义。