Caminos J E, Nogueiras R, Gaytán F, Pineda R, González C R, Barreiro M L, Castaño J P, Malagón M M, Pinilla L, Toppari J, Diéguez C, Tena-Sempere M
Department of Physiology, University of Santiago de Compostela, Santiago de Compostela, Spain.
Endocrinology. 2008 Jul;149(7):3390-402. doi: 10.1210/en.2007-1582. Epub 2008 Apr 10.
Adiponectin is an adipocyte hormone, with relevant roles in lipid metabolism and glucose homeostasis, recently involved in the control of different endocrine organs, such as the placenta, pituitary and, likely, the ovary. However, whether as described previously for other adipokines, such as leptin and resistin, adiponectin is expressed and/or conducts biological actions in the male gonad remains unexplored. In this study, we provide compelling evidence for the expression, putative hormonal regulation, and direct effects of adiponectin in the rat testis. Testicular expression of adiponectin was demonstrated along postnatal development, with a distinctive pattern of RNA transcripts and discernible protein levels that appeared mostly located at interstitial Leydig cells. Testicular levels of adiponectin mRNA were marginally regulated by pituitary gonadotropins but overtly modulated by metabolic signals, such as glucocorticoids, thyroxine, and peroxisome proliferator-activated receptor-gamma, whose effects were partially different from those on circulating levels of adiponectin. In addition, expression of the genes encoding adiponectin receptor (AdipoR)-1 and AdipoR2 was detected in the rat testis, with developmental changes and gonadotropin regulation for AdipoR2 mRNA, and prominent levels of AdipoR1 in seminiferous tubules. Moreover, recombinant adiponectin significantly inhibited basal and human choriogonadotropin-stimulated testosterone secretion ex vivo, whereas it failed to change relative levels of several Sertoli cell-expressed mRNAs, such as stem cell factor and anti-Müllerian hormone. In summary, our data are the first to document the expression, regulation and functional role of adiponectin in the rat testis. Taken together with its recently reported expression in the ovary and its effects on LH secretion and ovarian steroidogenesis, these results further substantiate a multifaceted role of adiponectin in the control of the reproductive axis, which might operate as endocrine integrator linking metabolism and gonadal function.
脂联素是一种脂肪细胞激素,在脂质代谢和葡萄糖稳态中发挥相关作用,最近还参与了对不同内分泌器官的调控,如胎盘、垂体,可能还有卵巢。然而,与之前描述的其他脂肪因子(如瘦素和抵抗素)一样,脂联素在雄性性腺中是否表达和/或发挥生物学作用仍未得到探索。在本研究中,我们提供了令人信服的证据,证明脂联素在大鼠睾丸中的表达、假定的激素调节及其直接作用。脂联素在出生后的发育过程中在睾丸中表达,具有独特的RNA转录本模式和可辨别的蛋白质水平,主要出现在间质的睾丸间质细胞中。脂联素mRNA的睾丸水平受垂体促性腺激素的轻微调节,但明显受代谢信号如糖皮质激素、甲状腺素和过氧化物酶体增殖物激活受体γ的调节,其作用与对循环中脂联素水平的影响部分不同。此外,在大鼠睾丸中检测到了编码脂联素受体(AdipoR)-1和AdipoR2的基因表达,AdipoR2 mRNA有发育变化和促性腺激素调节,而AdipoR1在生精小管中的水平较高。此外,重组脂联素在体外显著抑制基础和人绒毛膜促性腺激素刺激的睾酮分泌,而它未能改变几种支持细胞表达的mRNA(如干细胞因子和抗苗勒管激素)的相对水平。总之,我们的数据首次记录了脂联素在大鼠睾丸中的表达、调节和功能作用。结合其最近在卵巢中的表达及其对促黄体生成素分泌和卵巢类固醇生成的影响,这些结果进一步证实了脂联素在生殖轴调控中的多方面作用,它可能作为连接代谢和性腺功能的内分泌整合因子发挥作用。