Circulating IGF-binding protein 7 (IGFBP7) levels are elevated in patients with endometriosis or undergoing diabetic hemodialysis.
BACKGROUND
Insulin-like growth factor-binding protein-7 (IGFBP7) is a secretory protein with a molecular mass of approximately 30 kDa. It is abundantly expressed in the uterine endometrium during the secretory phase of the menstrual cycle. Decreased IGFBP7 expression has been observed in some cancers and leiomyomata.


METHODS
To determine whether serum IGFBP7 levels reflect changes in uterine IGFBP7 expression in humans during the menstrual cycle, and to examine whether serum IGFBP7 levels are altered in patients with various disorders, we developed a novel, dual-antibody sandwich enzyme-linked immunosorbent assay (ELISA). Firstly, concentrations of IGFBP7 released into the medium were determined in cultured endometrial stromal and glandular cells. Blood samples were collected from women who had normal menstrual cycles and who had been diagnosed with endometriosis. Serum from hemodialysis patients and gastrointestinal cancers was also used to determine the IGFBP7 levels.


RESULTS
Using this new ELISA, we demonstrated that cultured uterine cells secrete IGFBP7 into the medium. Patients with endometriosis and those with type II diabetes mellitus undergoing hemodialysis had significantly higher serum concentrations of IGFBP7 than the relevant control subjects. There were no differences in serum IGFBP7 levels in women at different stages of the menstrual cycle. Furthermore, serum IGFBP7 levels in patients with colorectal, esophageal, or endometrial cancer were not different than normal healthy subjects.


CONCLUSIONS
Our observations suggest that IGFBP7 is associated with the pathophysiology of endometriosis and diabetes mellitus, and that serum IGFBP7 levels do not reflect enhanced uterine expression of IGFBP7 mRNA during the menstrual cycle.
Kutsukake
Masahiko
M
Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 193-0392, Japan. kutsu@ps.toyaku.ac.jp
Ishihara
Ryosuke
R
Momose
Katsutoshi
K
Isaka
Keiichi
K
Itokazu
Osamu
O
Higuma
Chinatsu
C
Matsutani
Takeshi
T
Matsuda
Akihisa
A
Sasajima
Koji
K
Hara
Takahiko
T
Tamura
Kazuhiro
K
D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000628:therapy; D004715:Endometriosis / Q000097:blood* / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D008297:Male; D008597:Menstrual Cycle / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D006435:Renal Dialysis; D015854:Up-Regulation; D014591:Uterine Diseases / Q000097:blood* / Q000150:complications; D055815:Young Adult
D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1