title: Gene expression of a truncated and the full-length growth hormone (GH) receptor in subcutaneous fat and skeletal muscle in GH-deficient adults: impact of GH treatment.
abstract: In humans at least two GH receptors are significantly expressed. One is the full-length receptor (GHR); the other is a truncated form (GHRtr), that lacks most of the intracellular domain. This receptor may inhibit the action of the full-length receptor. Circulating GH-binding protein (GHBP) is a proteolytically cleaved product from both of these receptors. The clinical relevance of the different receptor types is unknown. We examined the gene expression of GHR and GHRtr in human adipose tissue and skeletal muscle and the influence of GH treatment on this expression. Furthermore, we studied the relationship of circulating GHBP and body composition to GHR and GHRtr gene expression. Eleven adult GH-deficient patients were studied before and after 4 months of GH substitution therapy. Abdominal fat obtained by liposuction and femoral muscle biopsies were taken at baseline and after 4 months. Gene expression of GHR and GHRtr in adipose tissue and skeletal muscle was determined and expressed relative to the expression of beta-actin. Gene expression of GHR in abdominal sc adipose tissue was not altered, whereas the expression of GHRtr increased significantly. In skeletal muscle inverse changes were seen in the expression of messenger ribonucleic acid (mRNA) levels for the two GH receptor forms: expression of GHR increased significantly, whereas mRNA levels for GHRtr decreased. As expected, body composition changed with reduction of body fat mass after 4 months of GH treatment. Levels of circulating GHBP decreased significantly. We conclude that GH treatment in GH-deficient adults changes the expression of mRNA for GHR and GHRtr in adipose tissue and skeletal muscle. Whether these changes are responsible for the observed changes in body composition in response to GH treatment and the observed changes in levels of circulating GHBP, however, needs further elucidation.
authors.affiliation: Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, DK-8000 Aarhus. sanne.fisker@dadlnet.dk
authors.forename: S
authors.initials: S
authors.lastname: Fisker
authors.forename: K
authors.initials: K
authors.lastname: Kristensen
authors.forename: A M
authors.initials: AM
authors.lastname: Rosenfalck
authors.forename: S B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: L
authors.initials: L
authors.lastname: Ebdrup
authors.forename: B
authors.initials: B
authors.lastname: Richelsen
authors.forename: J
authors.initials: J
authors.lastname: Hilsted
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: J O
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001823:Body Composition; D002352:Carrier Proteins / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011986:Receptors, Somatotropin / Q000235:genetics*; D012867:Skin; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein