title: Growth Hormone and Insulin Signaling in Acromegaly: Impact of Surgery Versus Somatostatin Analog Treatment.
abstract: Somatostatin analogs (SAs) used in acromegaly to suppress GH secretion and tumor growth also suppress insulin secretion and may impact GH signaling.
  
  
  
  To compare GH and insulin signaling after iv GH exposure in acromegalic patients controlled by surgery (n = 9) or SA (n = 9).
  
  
  
  Each patient was studied for 3 hours after an overnight fast (t = -60 to 120 minutes). GH was administered at t = 0 minutes; muscle and fat biopsies were obtained at t = 0 minutes and at t = 30 minutes (muscle) and t = 120 minutes (fat). Interstitial fluid was obtained from skin suction blisters (t = 0 minutes).
  
  
  
  GH and insulin signalling in muscle and fat. GH and IGF-1 in serum and interstitial fluid; insulin and free fatty acids in serum.
  
  
  
  The groups were comparable as regards GH and IGF-1. The SA group exhibited higher free fatty acid and glucose levels; basal suppressor of cytokine signaling protein 1 (SOCS1) mRNA in fat was increased in the SA group and correlated positively with SA dose (r2= 0.54; P = .04). GH-induced GH signalling (pSTAT5b) in muscle occurred in both groups together with increased expression of SOCS and CISH genes. GH-induced pAKTthr308was observed in SA patients. In both groups, mRNA expression of phosphatase and tensin homolog, a suppressor of insulin signaling, increased in fat after GH.
  
  
  
  1) Signatures of GH and insulin signaling differ as a function of acromegaly treatment modality. 2) Extra-pituitary effects of SA may account for this. 3) The clinical implications remain to be investigated.
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Dal
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Katrine Lundby
authors.initials: KL
authors.lastname: Høyer
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Steen Bønløkke
authors.initials: SB
authors.lastname: Pedersen
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Nils Erik
authors.initials: NE
authors.lastname: Magnusson
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Bjerring
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.affiliation: Medical Research Laboratory (J.D., K.L.H., S.B.P., N.E.M., J.F., N.M., J.O.L.J.), Department of Clinical Medicine, Health, Aarhus University, and Department of Endocrinology, Aarhus University Hospital, 8000 Aarhus, Denmark; Department of Clinical Pharmacology (N.J.), University of Aarhus, 8000 Aarhus, Denmark; and Mølholm Research (P.B.), Mølholm Hospital, 7100 Vejle, Denmark.
authors.forename: Jens Otto Lunde
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000172:Acromegaly / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D000273:Adipose Tissue / Q000378:metabolism; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010043:Outcome and Process Assessment, Health Care; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000032:analysis / Q000494:pharmacology*
chemical_list: D007328:Insulin; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I