Insulin-like growth factor I stimulates the synthesis and release of prolactin from human decidual cells.
Recent studies suggest a role for insulin-like growth factor I (IGF-I) in the regulation of hormone release from placental, gonadal, and pituitary tissues. To examine whether IGF-I may also regulate the release of PRL from human decidual tissue, we have investigated the effect of recombinant human IGF-I on PRL release from monolayer cultures of human decidual cells exposed to IGF-I for up to 4 days. IGF-I (10-1000 ng/ml) stimulated a sustained dose-dependent increase in PRL release (half-maximal concentration, 25 ng/ml) beginning 48 h after initial exposure, but had no effect on the intracellular PRL content. The amounts of PRL released from maximally stimulated cultures on days 3 and 4 were 168 +/- 3% (mean +/- SEM) and 258 +/- 8% of control values, respectively. IGF-I-mediated effects were inhibited by cycloheximide (3.6 microM), suggesting that the increase in PRL was the result of newly synthesized hormone. The increase in PRL release was not due to a generalized effect on protein release, since IGF-I had no effect on the release of trichloroacetic acid-precipitable [35S]methionyl proteins. Radioligand competition studies indicate that the biological actions of IGF-I are mediated through interaction with the IGF-I receptor. Binding of radiolabeled IGF-I to decidual cells in suspension was specific, saturable, and displacable by unlabeled IGF-I, with a potency nearly 10 times greater than that of insulin. Furthermore, exposure of decidual cells to a monoclonal antibody to the IGF-I receptor (alpha-IR3) completely inhibited both IGF-I-mediated PRL release and specific binding of [125I]IGF-I to decidual cells. Since the actions of IGF-I occurred at physiological concentrations, these findings strongly support a role for IGF-I in the regulation of PRL secretion by human decidua.
Thrailkill
K M
KM
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Golander
A
A
Underwood
L E
LE
Handwerger
S
S
D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism*; D011972:Receptor, Insulin / Q000276:immunology / Q000502:physiology; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000494:pharmacology; D013002:Somatomedins / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D003513:Cycloheximide; D011972:Receptor, Insulin