Regulation of insulin-like growth factor-binding protein-1 production in human granulosa-luteal cells.
Human follicular fluid contains the insulin-like growth factor-binding protein (IGFBP-1) synthesized by ovarian granulosa cells. We studied the regulation of IGFBP-1 production by the granulosa-luteal cells from the hyperstimulated follicles of patients attending an in vitro fertilization program. The cells were first allowed to attach and recover from the hyperstimulation for 2 days. Then, a protein kinase-C activator, 12-O-tetradecanoyl phorbol-13-acetate (TPA), and adenylate cyclase activators, gonadotropins, FSH, hCG, cholera toxin, or prostaglandin E2 (PGE2) were added to the cells. The gonadotropins failed to increase IGFBP-1 production, whereas it was enhanced by TPA and to a lesser extent by cholera toxin and PGE2. The maximal response to TPA occurred at the concentration of 1.0 ng/mL, and the enhancing effect of TPA was detected at 24 h. PGE2 stimulated IGFBP-1 production; the lowest effective concentration was 10(-8) mol/L. The mean highest response was 4.3-fold and occurred at the PGE2 concentration of 10(-5) mol/L. The effect of PGE2 on IGFBP-1 production became detectable at 24 h, and it continued to increase up to 72 h. PGE2 also increased granulosa-luteal cell progesterone production in a dose- and time-dependent manner. Incorporation of [35S]methionine into immunoreactive IGFBP-1, as detected by sodium dodecyl sulfate-polyacrylamide electrophoresis and fluorography, was also increased by TPA. This suggests that TPA accelerated the synthesis of IGFBP-1. Our results indicate that the production of IGFBP-1 by human granulosa-luteal cells can be regulated both via protein kinase-C- and adenylate cyclase-dependent pathways.
Jalkanen
J
J
Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland.
Suikkari
A M
AM
Koistinen
R
R
Bützow
R
R
Ritvos
O
O
Seppälä
M
M
Ranta
T
T
D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D011374:Progesterone / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin