Alternative splicing of placental lactogen (CSH2) in somatotroph pituitary adenomas

Neuro Endocrinol Lett. 2015;36(2):136-42.

Abstract

Objectives: Somatotroph adenomas secrete supraphysiological amounts of GH, causing acromegaly. We have previously shown epithelial splicing regulator 1 (ESRP1) to play a role in epithelial mesenchymal transition (EMT) progression in these adenomas and account for poor treatment response. We evaluated if the mRNA levels of the GH/CSH gene cluster in somatotroph adenomas are associated with an epithelial phenotype and response to SA treatment.

Methods: We investigated the associations between ESRP1 and the growth hormone/chorionic somatomammotropin (GH/CSH) gene cluster by RNA sequencing (RNAseq). CSH2 isoform 3 mRNA was further evaluated in 65 somatotroph adenomas and associations with disease severity and treatment response.

Results: mRNA for all genes in the GH/CSH cluster were expressed, however, only chorionic somatomammotropin 2/placental lactogen 2 (CSH2) displayed an alternative splicing pattern. CSH2 isoform 3 was associated with a dense granulation pattern and an epithelial phenotype with high levels of ESRP1 and E-cadherin expression. Further, CSH2 isoform 3 was associated with reduced serum GH and IGF-I levels after somatostatin analog treatment.

Conclusions: Attenuated CSH2 isoform 3 was associated with mesenchymal phenotype and a blunted clinical response to somatostatin analog treatment in patients with acromegaly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alternative Splicing / genetics*
  • Female
  • Growth Hormone-Secreting Pituitary Adenoma / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pituitary Neoplasms / genetics*
  • Placental Lactogen / genetics*

Substances

  • Placental Lactogen