Leptin and leptin receptor expression in normal and neoplastic human pituitary: Evidence of a regulatory role for leptin on pituitary cell proliferation
Leptin and leptin receptor expression in normal and neoplastic human pituitary: Evidence of a regulatory role for leptin on pituitary cell proliferation
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DOI：
10.1210/jc.84.8.2903
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发表时间：
1999-08-01
影响因子：
5.8
通讯作者：
Lloyd, RV
中科院分区：
文献类型：
--
作者：
Jin, L;Burguera, BG;Lloyd, RV
瘦素是一种由脂肪和其他一些组织分泌的循环激素。瘦素受体由单一跨膜多肽组成，其作为长的生理学重要形式以及以几种短的同种型存在。最近的研究表明，在动物模型中，垂体前叶可能在瘦素的调节作用中起作用。为了验证这种可能性，在人类垂体，我们检查了瘦素和OB-R在正常和肿瘤垂体的表达，瘦素在垂体中的可能功能也进行了分析。瘦素存在于20-25%的垂体前叶细胞中，并在大多数正常垂体前叶细胞中表达，包括ACTH（70%的ACTH细胞）、GH（21%）、FSH（33%）、LH（29%）、TSH（32%）和卵泡星状细胞（64%），但与极少数PRL细胞（3%）共定位，如用两种不同的抗瘦素抗体通过双标记免疫组织化学检测的。此外，瘦素的表达检测RT-PCR在一些垂体肿瘤，包括促肾上腺皮质激素（3/4），生长激素（1/4），空细胞（2/4），促性腺激素（1/4）肿瘤以及在正常垂体。免疫组织化学染色显示，瘦素在正常垂体腺瘤的免疫反应性。用瘦素处理永生化培养的垂体前叶细胞系HP 75，体外刺激胰抑素分泌。瘦素还抑制人HP 75和大鼠垂体GH（3）细胞系的细胞生长。长（OB-Rb）和普通（OB-Ra）形式的瘦素受体信使核糖核酸和瘦素受体蛋白在正常和肿瘤垂体前叶细胞中表达。这些研究结果首次表明，瘦素是由大多数人垂体前叶细胞类型的表达，并有减少瘦素蛋白免疫反应性垂体腺瘤相比，在正常垂体组织。我们还表明，OB-Rb是广泛表达的正常和肿瘤垂体前叶细胞，涉及自分泌/旁分泌环的生产和调节瘦素在垂体。
Leptin is a circulating hormone secreted by adipose and a few other tissues. The leptin receptor consists of a single transmembrane-spanning polypeptide that is present as a long physiologically important form as well as in several short isoforms. Recent studies have suggested that the anterior pituitary may have a role in the regulatory effects of leptin in animal models. To test this possibility in human pituitaries, we examined the expression of leptin and OB-R in normal and neoplastic pituitaries, and the possible functions of leptin in the pituitary were also analyzed. Leptin was present in 20-25% of anterior pituitary cells and was expressed in most normal anterior pituitary cells, including ACTH (70% of ACTH cells), GH (21%), FSH (33%), LH (29%), TSH (32%), and folliculo-stellate cells (64%), but was colocalized with very few PRL cells (3%), as detected by double labeling immunohistochemistry with two different antileptin antibodies. In addition, leptin expression was detected by RT-PCR in some pituitary tumors, including ACTH (three of four), GH (one of four), null cells (two of four), and gonadotroph (one of four) tumors as well as in normal pituitary. Immunohistochemical staining showed greater immunoreactivity for leptin in normal pituitaries compared to adenomas. Treatment of an immortalized cultured anterior pituitary cell line, HP75, with leptin stimulated pancreastatin secretion in vitro. Leptin also inhibited cell growth in the human HP75 and in the rat pituitary GH(3) cell lines. Both long (OB-Rb) and common (OB-Ra) forms of the leptin receptor messenger ribonucleic acid and leptin receptor protein were expressed in normal and neoplastic anterior pituitary cells. These findings show for the first time that leptin is expressed by most human anterior pituitary cell types and that there is decreased leptin protein immunoreactivity in pituitary adenomas compared to that in normal pituitary tissues. We also show that OB-Rb is widely expressed by normal and neoplastic anterior pituitary cells, implicating an autocrine/paracrine loop in the production and regulation of leptin in the pituitary.