Barreiro M L, Suominen J S, Gaytán F, Pinilla L, Chopin L K, Casanueva F F, Diéguez C, Aguilar E, Toppari J, Tena-Sempere M
Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Spain.
Biol Reprod. 2003 May;68(5):1631-40. doi: 10.1095/biolreprod.102.008862. Epub 2002 Nov 27.
Recent evidence from our research suggested the direct role of ghrelin in the control of testicular function. However, the pattern of expression and hormonal regulation of the gene encoding its cognate receptor (i.e., the growth hormone-secretagogue receptor [GHS-R]) in the male gonad remains to be fully elucidated. In this paper, overall expression of GHS-R mRNA in rat testis was compared with that of the functional receptor form, namely GHS-R type 1a, in different developmental and experimental settings. In addition, cellular distribution of GHS-R within adult testis tissue was assessed. Our analyses demonstrated persistent expression of the GHS-R gene in rat testis throughout postnatal development. In contrast, testicular expression of GHS-R type 1a mRNA remained undetectable before puberty and sharply increased thereafter. In adult testis, GHS-R1a mRNA expression presented a scattered pattern of cellular distribution, including Sertoli and Leydig cells that also showed specific GHS-R1a immunoreactivity. Expression of total GHS-R and specific GHS-R1a mRNAs was detected in isolated seminiferous tubule preparations, with varying levels throughout the defined stages of the spermatogenic cycle. In addition, testicular expression of total GHS-R and GHS-R1a mRNAs was up-regulated by exposure to ghrelin in vitro and after stimulation with FSH in vivo. In conclusion, our data demonstrate that expression of the GHS-R gene in rat testis takes place in a developmental, stage-specific, and hormonally regulated manner. Divergent expression of total GHS-R and type 1a specific mRNAs was detected at certain stages of postnatal development and spermatogenic cycle, thus raising the possibility that, in addition to net changes in GHS-R gene expression, the balance between receptor subtypes may represent a novel mechanism for the tuning of ghrelin sensitivity in rat testis.
我们研究的最新证据表明,胃饥饿素在睾丸功能控制中具有直接作用。然而,其同源受体(即生长激素促分泌素受体[GHS-R])编码基因在雄性性腺中的表达模式和激素调节仍有待充分阐明。在本文中,我们比较了在不同发育和实验条件下,大鼠睾丸中GHS-R mRNA的整体表达与功能性受体形式(即1a型GHS-R)的表达。此外,还评估了GHS-R在成年睾丸组织中的细胞分布。我们的分析表明,GHS-R基因在大鼠睾丸出生后的整个发育过程中持续表达。相比之下,1a型GHS-R mRNA在青春期前的睾丸中未检测到表达,此后急剧增加。在成年睾丸中,GHS-R1a mRNA表达呈现出分散的细胞分布模式,包括支持细胞和间质细胞,这些细胞也显示出特异性的GHS-R1a免疫反应性。在分离的生精小管制剂中检测到总GHS-R和特异性GHS-R1a mRNA的表达,在生精周期的不同阶段表达水平有所不同。此外,体外暴露于胃饥饿素和体内用促卵泡激素刺激后,睾丸中总GHS-R和GHS-R1a mRNA的表达上调。总之,我们的数据表明,大鼠睾丸中GHS-R基因的表达以发育、阶段特异性和激素调节的方式进行。在出生后发育和生精周期的某些阶段检测到总GHS-R和1a型特异性mRNA的差异表达,因此增加了一种可能性,即除了GHS-R基因表达的净变化外,受体亚型之间的平衡可能代表了一种调节大鼠睾丸中胃饥饿素敏感性的新机制。