Cellular location and hormonal regulation of ghrelin expression in rat testis

Cellular location and hormonal regulation of ghrelin expression in rat testis
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DOI:
10.1095/biolreprod.102.006965
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发表时间:
2002-12-01
影响因子:
3.6
通讯作者:
Tena-Sempere, M
Tena-Sempere, M
中科院分区:
生物学2区
文献类型:
--
作者:
Barreiro, ML;Gaytán, F;Tena-Sempere, M

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Ghrelin是生长激素促分泌素受体的内源性配体,是最近克隆的一种由28个氨基酸组成的多肽,主要在胃和下丘脑表达,具有刺激生长激素(GH)释放和食物摄取的能力。然而,已经提出了Ghrelin额外的、尚不清楚的生物学作用的可能性。作为我们最近关于Ghrelin在大鼠睾丸中表达和功能作用的最新发现的继续,我们报道了在出生后发育和选择性间质细胞消除后Ghrelin多肽在大鼠睾丸中的细胞表达模式,并在不同的实验模型中从mRNA和/或蛋白水平评估了激素对睾丸Ghrelin表达的调节。出生后发育过程中的免疫组织化学分析表明,Ghrelin多肽在大鼠睾丸中有选择性地定位于成熟的胎儿和成人型间质细胞中。在选择性间质细胞撤除后,Ghrelin蛋白似乎在睾丸间质中检测不到,这一点与此一致。在激素调节方面,长期切除垂体后,睾丸ghrelin mRNA和蛋白的表达下降到可以忽略的水平,而用人绒毛膜促性腺激素(CG)(作为促黄体生成素的超级激动剂)替代部分恢复了ghrelin的mRNA和肽的表达。此外,急性给予人CG(25IU)可引起正常大鼠睾丸Ghrelin mRNA表达的一过性升高,在注射后4h达到峰值,这是FSH(12.5IU/只)所不能达到的。相反,在生长激素缺乏的大鼠、在甲亢和甲状腺功能减退的情况下,以及在肾上腺切除的动物中,Ghrelin mRNA的表达没有改变。总之,我们的结果表明,成熟的间质细胞是大鼠睾丸中Ghrelin表达的来源,该蛋白在胎儿和成人型间质细胞中都有表达。此外,我们的数据表明,睾丸Ghrelin的表达是受激素调节的,至少部分依赖于垂体促黄体生成素。
Ghrelin, the endogenous ligand for the growth hormone-secretagogue receptor, is a recently cloned 28-amino acid peptide, expressed primarily in the stomach and hypothalamus, with the ability to stimulate growth hormone (GH) release and food intake. However, the possibility of additional, as yet unknown biological actions of ghrelin has been suggested. As a continuation of our recent findings on the expression and functional role of ghrelin in rat testis, we report here the pattern of cellular expression of ghrelin peptide in rat testis during postnatal development and after selective Leydig cell elimination, and we assess hormonal regulation of testicular ghrelin expression, at the mRNA and/or protein levels, in different experimental models. Immunohistochemical analyses along postnatal development demonstrated selective location of ghrelin peptide within rat testis in mature fetal- and adult-type Leydig cells. In good agreement, ghrelin protein appeared undetectable in testicular interstitium after selective Leydig cell withdrawal. In terms of hormonal regulation, testicular ghrelin mRNA and protein expression decreased to negligible levels after long-term hypophysectomy, whereas replacement with human chorionic gonadotropin (CG) (as superagonist of LH) partially restored ghrelin mRNA and peptide expression. Furthermore, acute administration of human CG (25 IU) to intact rats resulted in a transient increase in testicular ghrelin mRNA levels, with peak values 4 h after injection, an effect that was not mimicked by FSH (12.5 IU/rat). In contrast, testicular expression of ghrelin mRNA remained unaltered in GH-deficient rats, under hyper- and hypothyroidism conditions, as well as in adrenalectomized animals. In conclusion, our results demonstrate that mature Leydig cells are the source of ghrelin expression in rat testis, the protein being expressed in both fetal- and adult-type Leydig cells. In addition, our data indicate that testicular expression of ghrelin is hormonally regulated and is at least partially dependent on pituitary LH.