Insulin stimulates the synthesis and release of prolactin from human decidual cells.
Insulin-like growth factor I (IGF-I) and insulin have been implicated in the regulation of differentiated functions in many cells. We have reported that IGF-I stimulates the release of decidual PRL, acting through the type I IGF receptor (1). To determine whether insulin regulates the synthesis and secretion of decidual PRL, monolayer cultures of human decidual cells were exposed to insulin at concentrations ranging from 10 ng to 10 micrograms/ml for up to 5 days. Insulin stimulated a dose-dependent increase in PRL release (half-maximal concentration, 50 ng/ml), beginning 48 h after initial exposure. Insulin-exposed cells released 62 +/- 2% (mean +/- SEM), 97 +/- 3% and 82 +/- 6% more PRL than control cultures on days 3, 4, and 5, respectively. Insulin also stimulated de novo PRL synthesis. During the final 24-h culture period, insulin-exposed cells released 73 +/- 7% more immunoprecipitable [35S]-methionyl PRL than control cells, comparable to the 60 +/- 7% increase in PRL (by RIA) during the same period. Insulin effects were relatively specific to PRL, since insulin had a much smaller effect on the synthesis of total trichloroacetic acid-precipitable proteins. Additionally, insulin had no significant effect on cell number, total DNA, or total cellular protein. Specific and saturable insulin-binding sites were observed in decidual cells, and polyclonal antibodies to the insulin receptor acted as insulin agonists, stimulating an increase in PRL release comparable to that produced by insulin alone. These observations suggest that the responses to insulin are mediated through the insulin receptor. Furthermore, our studies suggest that insulin may have a role in the regulation of PRL synthesis and release from human decidua.
Thrailkill
K M
KM
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Golander
A
A
Underwood
L E
LE
Richards
R G
RG
Handwerger
S
S
D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D011247:Pregnancy; D011388:Prolactin / Q000096:biosynthesis* / Q000378:metabolism; D014176:Protein Biosynthesis; D011972:Receptor, Insulin / Q000378:metabolism
D007328:Insulin; D011388:Prolactin; D003513:Cycloheximide; D011972:Receptor, Insulin