Expression of Pit-1 and Growth Hormone-Releasing Hormone Receptor mRNA in Human Pituitary Adenomas: Difference Among Functioning, Silent, and Other Nonfunctioning Adenomas

Abstract

We analyzed the expression of Pit-1 and growth hormone-releasing hormone receptor (GHRH-R) mRNA in various types of functioning and nonfunctioning adenomas using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) method. Among clinically nonfunctioning adenomas, tumors considered as silent adenomas were reclassified on a pathologic basis. Competitive RT-PCR showed that the levels of Pit-1 and GHRH-R mRNA expression in silent somatotroph adenomas and silent prolactinomas were similar to those in the corresponding functioning adenomas. In silent thyrotroph adenomas, both mRNAs showed high levels of expression that were similar to those in functioning and silent somatotroph adenomas. The results suggest that the cause of the silence in these tumors seems to be in the downstream to transcription of Pit-1 gene in the signaling pathway leading to hormone secretion. Competitive RT-PCR assay could distinguish silent adenomas of the Pit-1 group from the other nonfunctioning adenomas in the expression levels of Pit-1 and GHRH-R mRNAs. In the future, precise diagnosis of various adenomas may become possible by assaying transcription factors such as steroidogenic factor-1 and thyrotroph embryonic factor, which are thought to be related to adenohypophyseal cytodifferentiation.

Histopathological Review of Silent Pituitary Somatotroph Adenoma

“…Another cause of amenorrhea and galactorrhea is concomitant secretion of PRL from silent somatotroph adenomas that was often observed in previous reports, and was also observed in our patients [10][11][12][13]. The third possible cause is the so-called stalk section effect, as suggested by Kobayashi et al [7], that can cause mild hyperprolactinemia.…”

“…The majority of silent somatotroph adenomas were sparsely granulated adenomas [6,8,14,15,[18][19][20], as shown in the Table 1. Densely granulated type of silent somatotroph adenoma was also reported by several investigators [7,[10][11][12][13][14]18]. These paradoxical responses of GH in TRH or GnRH provocation test, which were used as a hallmark of silent somatotroph adenoma in our previous reports [10][11][12][13], are observed primarily in densely granulated somatotroph adenomas.…”

Subclinical hyperfunctioning pituitary adenomas: The silent tumors

“…In silent somatotroph, thyrotroph, and lactotroph adenomas Pit-1 and GHRH-R mRNA expression by RT-PCR was similar to functioning tumor counterparts (21). Pit-1 and GATA-2 are expressed in the nuclei of all silent thyrotroph adenomas, similar to functioning adenomas (22), suggesting that the cause of the silence of these tumors occurs downstream to the Pit-1 gene in the signaling pathway leading to hormone secretion.…”

Abnormal dynamics of growth hormone after thyrotropin-releasing hormone loading test, gonadotropin-releasing hormone loading test, and oral glucose tolerance test in mixed gonadal dysgenesis with a pituitary lesion

“…Nevertheless, it may be evoked by a GHsecreting adenoma, although the pathology of pituitary lesion is not verified. Clinically silent somatotroph adenoma has been reported by several investigators, and this condition frequently has menstrual disorder [1][2][3][4][5][6][7][8][9][10].…”