title: Alternative splicing of placental lactogen (CSH2) in somatotroph pituitary adenomas.
abstract: OBJECTIVE
  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.
authors.affiliation: Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway.
authors.forename: Tove
authors.initials: T
authors.lastname: Lekva
authors.affiliation: Institute of Clinical Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Jens Petter
authors.initials: JP
authors.lastname: Berg
authors.affiliation: Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors.forename: Robert
authors.initials: R
authors.lastname: Lyle
authors.affiliation: Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway.
authors.forename: Ansgar
authors.initials: A
authors.lastname: Heck
authors.affiliation: Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Oslo, Norway.
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
mesh_terms: D000328:Adult; D017398:Alternative Splicing / Q000235:genetics*; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000235:genetics*; D010928:Placental Lactogen / Q000235:genetics*
chemical_list: D010928:Placental Lactogen