Zafar M, Ezzat S, Ramyar L, Pan N, Smyth H S, Asa S L
Department of Pathology, Mount Sinai Hospital, Toronto, Ontario, Canada.
J Clin Endocrinol Metab. 1995 Dec;80(12):3621-7. doi: 10.1210/jcem.80.12.8530610.
Estrogen affects the synthesis and release of several pituitary hormones. The estrogen receptor (ER), a member of the steroid hormone receptor family, is thought to mediate transcriptional effects in a cell-specific fashion. We investigated whether ER is expressed in specific hormone-producing cell types in the human pituitary and its adenomas. Pituitary adenomas (n = 34) were collected at the time of surgery, and normal glands were obtained from autopsy. Expression of ER messenger ribonucleic acid (mRNA) was determined by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. ER was also localized with immunohistochemistry and protein extraction. By RT-PCR, ER mRNA was found in the nontumorous pituitary and in pituitary adenomas expressing only PRL, in those producing GH and PRL, and in adenomas expressing the gonadotropic hormones. No ER mRNA was detected in adenomas expressing only GH without PRL or gonadotropins, nor in tumors producing ACTH without PRL or gonadotropins. In situ hybridization was not as sensitive or specific as RT-PCR. Biochemical analysis performed on seven tumors that were positive for ER mRNA by RT-PCR detected ER protein in only one PRL adenoma and one oncocytoma and yielded negative or equivocal results in one PRL adenoma, three GH-PRL adenomas, and one null cell adenoma. ER protein was localized by immunohistochemistry in scattered cells of the nontumorous adenohypophysis and in a few PRL and gonadotroph adenomas. We conclude that ER expression, as determined by RT-PCR, correlates with the expression of PRL or gonadotropins; in contrast, ER mRNA was not detected in adenomas that express only GH or ACTH. These findings implicate ER as a cell-specific transcription factor that may regulate cytodifferentiation in the pituitary.
雌激素影响几种垂体激素的合成与释放。雌激素受体(ER)是类固醇激素受体家族的成员之一,被认为以细胞特异性方式介导转录效应。我们研究了ER是否在人垂体及其腺瘤的特定激素分泌细胞类型中表达。手术时收集垂体腺瘤(n = 34),并从尸检中获取正常腺体。通过逆转录 - 聚合酶链反应(RT-PCR)和原位杂交测定ER信使核糖核酸(mRNA)的表达。还通过免疫组织化学和蛋白质提取对ER进行定位。通过RT-PCR发现,在非肿瘤性垂体以及仅表达PRL的垂体腺瘤、分泌GH和PRL的腺瘤以及表达促性腺激素的腺瘤中存在ER mRNA。在仅表达GH而无PRL或促性腺激素的腺瘤中,以及在分泌ACTH而无PRL或促性腺激素的肿瘤中未检测到ER mRNA。原位杂交不如RT-PCR敏感或特异。对7个经RT-PCR检测ER mRNA呈阳性的肿瘤进行生化分析,仅在1个PRL腺瘤和1个嗜酸细胞瘤中检测到ER蛋白,而在1个PRL腺瘤、3个GH-PRL腺瘤和1个无功能细胞腺瘤中得到阴性或不确定结果。通过免疫组织化学将ER蛋白定位在非肿瘤性腺垂体的散在细胞以及少数PRL和促性腺激素细胞腺瘤中。我们得出结论,通过RT-PCR测定的ER表达与PRL或促性腺激素的表达相关;相反,在仅表达GH或ACTH的腺瘤中未检测到ER mRNA。这些发现表明ER是一种细胞特异性转录因子,可能调节垂体中的细胞分化。