Pit-1 gene expression in human lactotroph and somatotroph pituitary adenomas is correlated to D2 receptor gene expression.

ABSTRACT

The expression of the pituitary-specific transcription factor Pit-1 gene was analyzed in a series of 30 human lactotroph and somatotroph pituitary tumors. Northern blot analysis failed to reveal any quantitative differences in Pit-1 gene expression between somatotroph and lactotroph tumors, and reverse transcription-PCR analysis showed similar patterns of Pit-1 isoforms expression in both populations of tumors. The expression of the D2 receptor gene was subsequently analyzed in the same adenomas. In the prolactinomas, which presented with a variable sensitivity to dopamine agonist treatment, the intensity of the D2 receptor transcripts (2.8 kilobases) was variable and was related to the sensitivity to the dopamine agonist treatment. Notably, the individual D2 receptor messenger ribonucleic acid (mRNA) levels were highly correlated to the Pit-1 mRNA levels measured in the same tumors (r = 0.90; P < 0.0001). In the GH-secreting tumors, a significant expression of the D2 receptor gene was evidenced by Northern blot in all mixed somato-lactotroph adenomas and in some of the pure somatotroph adenomas; again, a positive correlation was found between D2 mRNA and Pit-1 mRNA levels (r = 0.68; P < 0.01). These results suggest the existence of mechanisms responsible for a coordinate control of Pit-1 and D2 receptor genes that remain to be determined.