title: Insulin-like growth factor-1 is associated with regulation of the luteinizing hormone production in men receiving androgen deprivation therapy with gonadotropin-releasing hormone analogues for localized prostate cancer.
abstract: BACKGROUND
  Luteinizing hormone (LH) during androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone analogues (GnRHa) has been thought to be biologically inactive, and the regulation of LH during ADT with GnRHa is thus unknown. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and differentiation, and IGF-1 production in the liver is dependent on growth hormone (GH) secretion from the anterior pituitary. Despite the presence of IGF-1 receptors in the gonadotroph, associations between the GH/IGF-1 and pituitary-gonadal axes, e.g., whether IGF-1 elicits the LH secretion, remain unclear.
  
  
  METHODS
  Seventy-one patients with localized prostate cancer, who received ADT with GnRHa, were prospectively studied based on their blood samples before treatment and after ADT for 6 months. We employed highly sensitive assays for measurement of serum testosterone (electrochemiluminescence immunoassay), GH/IGF-1 (radioimmunoassay), adrenocorticotropic hormone (ACTH: immunoradiometric assay), LH (chemiluminescent immunoassay), and dehydroepiandrosterone sulfate (DHEA-S: chemiluminescent enzyme immunoassay).
  
  
  RESULTS
  No correlation was noted between the pretreatment LH and IGF-1 levels; after ADT, the serum LH level was closely correlated with the IGF-1 concentration [Spearman's correlation coefficient (rs) = 0.370, P = 0.001]. The serum levels of androgens and gonadotropins reduced following ADT (P < 0.001 in all). The serum IGF-1 level increased (22 ± 6 nmol/L) compared with that at the baseline (19 ± 5 nmol/L) (P < 0.001), but no change was observed in the serum GH concentration between before and after ADT (1.4 ± 2.3 vs. 0.9 ± 0.9 μg/L, respectively, P = 0.691). The serum testosterone level was not correlated with the LH level either before or after ADT. The testosterone and DHEA-S levels after ADT were correlated with ACTH concentration (rs = 0.367, P = 0.002 and rs = 0.354, P = 0.002, respectively). We did not identify any correlations between the serum IGF-1 concentration and Gleason score, PSA value, or androgen levels.
  
  
  CONCLUSIONS
  During ADT with GnRHa, IGF-1 possibly promotes LH production, although its role is unclear. Associations among pituitary-gonadal, pituitary-adrenal, and GH/IGF-1 axes represented by IGF-1-mediated LH secretion and ACTH-mediated androgen synthesis are of interest, since both prostate epithelium proliferation and male anabolic activity are involved in these 3 axes. Assessment of oncologic outcomes is warranted for their significance in patients with prostate cancer.
authors: Division of Urology, Department of Regenerative and Transplant Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan. harasho@med.niigata-u.ac.jp
authors: Noboru
authors: N
authors: Hara
authors: Itsuhiro
authors: I
authors: Takizawa
authors: Etsuko
authors: E
authors: Isahaya
authors: Tsutomu
authors: T
authors: Nishiyama
authors: Tatsuhiko
authors: T
authors: Hoshii
authors: Fumio
authors: F
authors: Ishizaki
authors: Kota
authors: K
authors: Takahashi
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects; D017273:Goserelin / Q000008:administration & dosage; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016015:Logistic Models; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D013739:Testosterone / Q000097:blood
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D019382:Human Growth Hormone; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D005485:Flutamide; D000324:Adrenocorticotropic Hormone; D007986:Luteinizing Hormone; D017430:Prostate-Specific Antigen