ACTH and α-subunit are co-expressed in rare human pituitary corticotroph cell adenomas proposed to originate from ACTH-committed early pituitary progenitor cells
ACTH and α-subunit are co-expressed in rare human pituitary corticotroph cell adenomas proposed to originate from ACTH-committed early pituitary progenitor cells
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DOI：
10.1007/s12022-008-9014-6
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发表时间：
2008-03-01
影响因子：
4.4
通讯作者：
Osamura, Robert Yoshiyuki
中科院分区：
文献类型：
--
作者：
Suzuki, Masanori;Egashira, Noboru;Osamura, Robert Yoshiyuki
垂体细胞和腺瘤的功能分化遵循三种细胞谱系[生长激素-催乳素-促甲状腺激素谱系、促肾上腺皮质激素（ACTH）/阿黑皮素原（POMC）谱系和促卵泡激素（FSH）/促黄体激素（LH）谱系]中转录因子和辅因子的组合，所述细胞谱系包括Pit-1、加塔-2、SF-1、NeuroD 1/β 2、Tpit、ER α、等人只有很少的是来自不同谱系的激素在同一腺瘤细胞中共表达。大多数属于ACTH/POMC谱系的促肾上腺皮质激素细胞腺瘤是单激素的。在我们对89例促肾上腺皮质激素细胞腺瘤的研究中，5例同时表达ACTH和α亚单位，这些腺瘤不表达任何其他垂体前叶激素或亚单位。为了阐明相关机制，我们研究了调节垂体细胞分化的转录因子。ACTH/POMC谱系的标记物NeuroD 1和T-pit以及与LH/FSH细胞谱系相关的SF-1和DAX-1在所有病例中均表达。GATA 2，促性腺激素细胞系与SF-1的协同因子，也在5例中的3例表达。由于ACTH和α-亚单位是发育过程中最早出现的激素，我们推测这些特殊的腺瘤来源于定向ACTH祖细胞。这些腺瘤的功能分化的分子过程需要进一步研究。
The functional differentiation of pituitary cells and adenomas follows the combination of transcription factors and co-factors in three cell lineages [growth hormone-prolactin-thyroid-stimulating hormone lineage, adrenocorticotrophic hormone (ACTH)/pro-opiomelanocortin (POMC) lineage, and follicular stimulating hormone (FSH)/luteinizing hormone (LH) lineage], which include Pit-1, GATA-2, SF-1, NeuroD1/beta2, Tpit, ER alpha, and others. Only rarely are hormones from different lineages co-expressed in the same adenoma cells. Most corticotroph cell adenomas belonging to the ACTH/POMC lineage are mono-hormonal. In our study of 89 corticotroph cell adenomas, 5 cases expressed both ACTH and alpha-subunit; these adenomas did not express any other anterior pituitary hormones or subunits. To clarify the mechanism involved, we studied the transcription factors that regulate pituitary cell differentiation. NeuroD1 and T-pit, markers of the ACTH/POMC lineage, and SF-1 and DAX-1, related to the LH/FSH cell lineage were expressed in all cases. GATA2, a synergistic factor in the gonadotroph cell lineage with SF-1, was also expressed in three of five cases. As ACTH and alpha-subunit are the earliest hormones to appear during development, we speculate that these particular adenomas are derived from committed ACTH progenitor cells. The molecular process governing functional differentiation of these adenomas requires further investigation.