Alternative splicing of placental lactogen (CSH2) in somatotroph pituitary adenomas.
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....
Citation
Lekva T, Berg J, Lyle R, Heck A, Bollerslev J, Ueland T. Alternative splicing of placental lactogen (CSH2) in somatotroph pituitary adenomas. Neuro Endocrinol Lett. 2015 Jan; 36(2): 136-142