Correlation of alternative splicing of the D2 dopamine receptor mRNA and estrogen receptor mRNA in the prolactinomas and gonadotrope tumors

J Neurooncol. 2009 Aug;94(1):135-9. doi: 10.1007/s11060-009-9816-5. Epub 2009 Feb 28.

Abstract

Objective: Estradiol (E2) acts to modulate the ratio of two dopamine D2 receptor isoforms (D2L/D2S) by the nuclear estrogen receptor (ER) and to reduce dopamine's inhibitory action on PRL secretion. Here we demonstrate the correlation between the expression of ER mRNA and D2R mRNA isoforms in pituitary neoplasms cells.

Methods: Twenty-four human pituitary adenomas (14 prolactinomas and 10 gonadotrope tumors) were examined for the expression of both ER mRNA and D2R mRNA by means of semi-quantitative RT-PCR analysis.

Results: No significant difference was found in ERbeta mRNA expression levels between prolactinomas and gonadotrope tumors (P = 0.871), but there was a significant difference in the expression of ERalpha mRNA (P = 0.003). The significant difference was found between the two pituitary adenomas types in both levels of D2S and D2L mRNA expression (P = 0.036 and 0.007 respectively). Furthermore, both levels of expression in prolactinomas were significantly higher than that in gonadotrope tumors. Additionally, a negative correlation between D2S and ERalpha mRNA expression and a positive correlation between D2L and ERalpha mRNA expression were found in these tumors.

Conclusion: This study for the first time shows a good correlation between expression of ER and D2R isoforms in prolactinomas and gonadotrope tumors. Reducing the amount of the ERalpha in neoplasm cells can alter the ratio of D2L/D2S, which may increase the drug sensitivity of pituitary adenomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alternative Splicing / genetics*
  • Analysis of Variance
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pituitary Neoplasms / genetics*
  • Prolactinoma / genetics*
  • Protein Isoforms / genetics
  • RNA, Messenger / metabolism*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Estrogen / genetics*
  • Statistics as Topic
  • Young Adult

Substances

  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Receptors, Estrogen