title: The growth hormone (GH)-insulin-like growth factor axis during testosterone replacement therapy in GH-treated hypopituitary males.
abstract: Several studies suggest a direct effect of sex steroids on insulin-like growth factor-I (IGF-I) production. Oestrogen has been hypothesized directly to inhibit hepatic IGF-I production, but the role of androgens is not clarified. We aimed to investigate whether testosterone exerts a pituitary-independent effect on IGF-I and related parameters. Eight adult hypopituitary men (39.9 +/- 5.7 years) receiving growth hormone (GH) and testosterone replacement therapy (250 mg testosterone enantate every fourth week) participated in this prospective study. Frequent blood samples were drawn over a 5 week period in relation to two testosterone injections. Mean baseline IGF-I levels were 352 +/- 135 microg/L, and they remained unaltered during the study period (analysis of variance (ANOVA), P = 0.88). Free IGF-I levels did not change either (ANOVA, P = 0.35). Serum IGF binding protein-3 (IGFBP-3) and acid-labile subunit decreased (ANOVA, P = 0.04 and P = 0.02 respectively) but post hoc analysis did not reveal a particular difference between days. IGFBP-1 increased following testosterone administration (ANOVA, P = 0.05), whereas GH binding protein levels tended to decrease following testosterone administration (ANOVA, P = 0.08). Prostate-specific antigen tended slightly to increase after each testosterone injection (ANOVA, P = 0.08, post hoc, NS). We conclude that major changes in total IGF-I are not induced during conventional intramuscular testosterone replacement in GH-treated hypopituitary males, suggesting that testosterone effects on IGF-I are likely to be secondary to a stimulation of endogenous GH release.
authors.affiliation: Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Fisker
authors.forename: H
authors.initials: H
authors.lastname: Nørrelund
authors.forename: A
authors.initials: A
authors.lastname: Juul
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkebaek
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: J O
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000097:blood; D004958:Estradiol / Q000097:blood; D013006:Growth Hormone / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy*; D007273:Injections, Intramuscular; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017430:Prostate-Specific Antigen; C051815:somatotropin-binding protein