Regulation of insulin-like growth factor binding protein secretion by human granulosa luteal cells in a polycystic ovary-like environment.
OBJECTIVE
To determine the effect of androstenedione (A), insulin, and LH on secretion of insulin-like growth factor binding proteins (IGFBPs) from human granulosa luteal cells.


METHODS
Human granulosa cells were cultured for a total of 4 days in serum-free medium containing A (10(-6) mol/L), with or without insulin (100 microU/mL-800 microU/mL), LH (1 microU/mL-10 microg/L), and A (10(-5) mol/L).


METHODS
Granulosa cells were obtained from IVF procedures.


METHODS
Women undergoing IVF for tubal disease.


METHODS
None.


METHODS
Immunoassay and autoradiographs of Western ligand blotting detected IGFBP accumulations in the medium.


RESULTS
Cultured granulosa cells secreted IGFBP-1 through IGFBP-4. Insulin (100 microU/mL-800 microU/mL), LH (1 microg/L-10 microg/L), and A (10(-5) mol/L) caused a significant decrease in IGFBP-1 accumulation in the medium both alone and when added in combination. The release of IGFBP-2 and IGFBP-4 was significantly stimulated by insulin, whereas LH had no effect. Elevated levels of androgen (10(-5) mol/L) significantly stimulated the secretion of IGFBP-2, whereas the release of IGFBP-4 was reduced.


CONCLUSIONS
These results demonstrate that androgen and insulin are important regulators of IGFBP release and that elevated levels of the two hormones may contribute to the altered IGFBP profile found in PCOS follicles, compared with the case of estrogen-dominant follicles.
Greisen
Susanne
S
Department of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark. greisens@mail1.stofanet.dk
Flyvbjerg
Allan
A
Ledet
Thomas
T
Ovesen
Per
P
D000735:Androstenedione / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism
D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D020033:Protein Isoforms; D000735:Androstenedione; D007986:Luteinizing Hormone