title: The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas.
abstract: BACKGROUND
  There is no tumor-directed medical therapy available for Cushing's disease.
  
  
  OBJECTIVE
  The objective was to determine the in vitro effect of the somatostatin analog pasireotide (SOM230) on cell proliferation in human corticotroph tumors.
  
  
  METHODS
  Expression of somatostatin receptors (SSTR 1-5) was determined by quantitative RT-PCR in 13 human corticotroph tumors and by immunohistochemistry (IHC) in 12 of the 13 tumors. SOM230 effects on cell proliferation and ACTH release were evaluated in vitro using primary cultures of six of the 13 human corticotroph adenomas.
  
  
  RESULTS
  In our series, we found expression of SSTR subtypes 1, 2, 4, and 5 in human corticotroph tumors by quantitative RT-PCR. All receptor subtypes were detected by IHC, with SSTR subtype 5 having the highest IHC score in 83% (10 of 12) of the cases. Significant suppression of cell proliferation was observed in all tumors cultured (percent suppression range: 10-70%; P = 0.045-0.001). SOM230 inhibited ACTH secretion in five of the six tumors cultured (percent suppression range: 23-56%; P = 0.042-0.001).
  
  
  CONCLUSIONS
  Corticotroph tumors express multiple SSTR subtypes. SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. These in vitro results support the hypothesis that SOM230 may have a role in the medical therapy of corticotroph tumors.
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Dalia L
authors.initials: DL
authors.lastname: Batista
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.forename: Roger
authors.initials: R
authors.lastname: Gejman
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ansell
authors.forename: Yunli
authors.initials: Y
authors.lastname: Zhou
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Johnson
authors.forename: Brooke
authors.initials: B
authors.lastname: Swearingen
authors.forename: E Tessa
authors.initials: ET
authors.lastname: Hedley-Whyte
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
authors.forename: Anne
authors.initials: A
authors.lastname: Klibanski
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy*; D000236:Adenoma / Q000188:drug therapy*; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; D000324:Adrenocorticotropic Hormone; C517782:pasireotide