Sex steroid influence on cannabinoid CB1 receptor mRNA and endocannabinoid levels in the anterior pituitary gland
Sex steroid influence on cannabinoid CB1 receptor mRNA and endocannabinoid levels in the anterior pituitary gland
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DOI：
10.1006/bbrc.2000.2406
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发表时间：
2000-04-02
影响因子：
3.1
通讯作者：
Fernández-Ruiz, JJ
中科院分区：
文献类型：
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作者：
González, S;Bisogno, T;Fernández-Ruiz, JJ
最近的研究表明，发生内源性大麻素的合成和基因表达和免疫反应性的大麻素CB 1受体在垂体前叶。由于这个腺体的活动是在循环性类固醇的影响下，本研究旨在阐明是否在垂体前叶的CB 1受体基因的表达也受到这些类固醇的影响。为了这个目的，我们首先研究了可能的变化水平的CB 1受体mRNA转录在垂体前叶的完整的雄性大鼠和正常的周期性雌性大鼠在卵巢周期的不同阶段。我们观察到，男性有较高水平的CB 1受体mRNA转录比女性。此外，这些成绩单波动的女性在卵巢周期的不同阶段，观察到的最高值在发情间期的第二天和发情期的最低值。在这些动物中，我们还测量了垂体前叶和下丘脑中内源性大麻素的含量。我们观察到，在这两种情况下，女性的大麻素含量高于男性。雌鼠垂体前叶和下丘脑中大麻素的含量在卵巢周期中也有波动。垂体前叶在动情期最高，动情间期和动情前期第1天最低，下丘脑则相反。在其他主要内源性大麻素，2-花生四烯酸甘油，男性和女性之间，在卵巢周期中没有观察到变化。为了进一步探讨循环性类固醇对脑垂体前叶中CB 1受体基因表达的潜在影响，作为第二个目标，我们研究了性腺切除和性类固醇替代性腺切除大鼠中该受体转录本数量的可能变化。我们观察到，睾丸切除术（ORCHX）在男性降低CB 1受体mRNA水平，而与双氢睾酮替代也保持低水平的信使。在女性中，雌二醇替代卵巢切除（OVX）大鼠表现出显着较低的CB 1受体mRNA水平比OVX动物，没有被这种雌激素替代。在本实验中，我们还检查了先前报道的脑垂体前叶中CB 1受体基因对长期给予Delta（9）-四氢大麻酚（Delta（9）-THC）的反应是否受到性类固醇的影响。我们观察到，慢性Delta（9）-THC治疗降低了完整和ORCHX男性的CB 1受体mRNA水平，但在二氢睾酮替代的ORCHX男性中没有。在雌性中，Delta（9）-THC治疗对OVX和雌二醇替代OVX大鼠均无影响。总之，这些数据共同支持的CB 1受体基因的表达在垂体前叶调节性类固醇在男性和女性。此外，性腺类固醇似乎会影响该基因对慢性大麻素给药的反应。我们还观察到，在垂体前叶和下丘脑的大麻素含量可能是由循环性类固醇控制。这些数据的功能的影响进行了讨论。(C)北京大学出版社.
Recent studies have demonstrated the occurrence of endocannabinoid synthesis and of gene expression and immunoreactivity for the cannabinoid CB1 receptor in the anterior pituitary gland. Since the activity of this gland is under the influence of circulating sex steroids, the present study was designed to elucidate whether expression of the CB1 receptor gene in the anterior pituitary gland is also under the influence of these steroids. To this aim, we first examined the possible changes in the levels of CB1 receptor-mRNA transcripts in the anterior pituitary gland of intact male rats and normal cycling female rats at the different stages of the ovarian cycle. We observed that males had higher levels of CB1 receptor-mRNA transcripts than females. In addition, these transcripts fluctuated in females during the different phases of the ovarian cycle, with the highest values observed on the second day of diestrus and the lowest on estrus. In these animals, we also measured the content of endocannabinoids in the anterior pituitary gland and the hypothalamus. We observed that females had higher contents of anandamide than males in both cases. The content of anandamide in females also fluctuated during the ovarian cycle in both the anterior pituitary gland and the hypothalamus. The highest values in the anterior pituitary gland mere found in the estrus and the lowest on the first day of diestrus and proestrus, whereas the inverse tendency was found in the hypothalamus. No changes were observed in the other major endocannabinoid, 2-arachidonoyl-glycerol, between males and females and during the ovarian cycle. To further explore the potential influence of circulating sex steroids on CB1 receptor gene expression in the anterior pituitary gland, as a second objective, we examined the possible changes in the amount of transcripts for this receptor in gonadectomized and sex steroid-replaced gonadectomized rats of both sexes. We observed that orchidectomy (ORCHX) in males reduced CB1 receptor-mRNA levels, whereas replacement with dihydrotestosterone also maintained low levels of this messenger. In females, estradiol-replaced ovariectomized (OVX) rats exhibited significantly lower CB1 receptor-mRNA levels than OVX animals that had not been replaced with this estrogen. In this experiment, we also examined if the previously reported response of the CB1 receptor gene in the anterior pituitary lobe to chronic administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is under sex steroid influence. We observed that chronic Delta(9)-THC treatment decreased CB1 receptor-mRNA levels in intact and ORCHX males, but not in dihydrotestosterone-replaced ORCHX males. In females, Delta(9)-THC treatment produced no effect in both OVX- and estradiol-replaced OVX rats. In summary, these data collectively support that expression of the CB1 receptor gene in the anterior pituitary gland is regulated by sex steroids in both males and females. Furthermore, gonadal steroids appear to affect the response of this gene to chronic cannabinoid administration. We have also observed that anandamide contents in the anterior pituitary gland and the hypothalamus might be controlled by circulating sex steroids. The functional implications of these data are discussed. (C) 2000 Academic Press.