Epidermal growth factor and thyrotropin-releasing hormone interact synergistically with calcium to regulate prolactin mRNA levels.
The regulation of prolactin RNA sequences by Ca2+, epidermal growth factor (EGF), and thyrotropin-releasing hormone (TRH), singly and in combination, was studied in GH3 cells incubated in a chemically defined medium. Ca2+ increased all large prolactin RNA sequences in the nucleus, thus suggesting a transcriptional site of action. A recently developed cytoplasmic dot hybridization procedure was employed to study regulation of cytoplasmic prolactin mRNA. Ca2+ alone stimulated prolactin mRNA with a lag of between 3 and 9 h and yielded a sizable final increase (14- to 18-fold) of prolactin mRNA. With EGTA present to chelate any residual Ca2+, prolactin mRNA was not detectably increased by TRH, showing that TRH requires Ca2+ to stimulate prolactin mRNA. Under these conditions, prolactin mRNA was only slightly (4-fold) increased by EGF. Either peptide plus an optimal concentration of Ca2+ yielded a 60- to 70-fold increase in prolactin mRNA, showing that both EGF and TRH regulate prolactin mRNA synergistically with Ca2+.
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007700:Kinetics; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D011388:Prolactin; D002118:Calcium