Fibroblast growth factor-2 and epidermal growth factor modulate prolactin responses to TRH and dopamine in primary cultures.
Fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) are expressed in most tissues of the organism including pituitary. FGF-2 increases PRL levels and PRL mRNA in GH3 cells and primary cultures, and it has been involved in the lactotroph proliferation and hyperplasia. EGF also increases PRL levels in vitro. However, the effects of these two factors in the responses of lactotroph cells to TRH and dopamine (DA) remain to be clarified. In the present work we have studied the modulator activity of FGF-2 and EGF on in vitro PRL in responses to TRH and DA in primary cultures from in vivo vehicle- or estrogen (E2)-treated rats. We have found that FGF-2 (2 x 10(-11) M) prevents the EGF-induced dose-dependent increase in PRL levels in control cells, and reversed the EGF-stimulating effects in cells from E2-treated rats. Both FGF-2 (2 x 10(-11) M) and EGF (6.6 x 10(-9) M) significantly increase (>30% and >120%, respectively) the PRL levels in response to TRH (10(-6), 10(-5) M). FGF-2 blocked the inhibitory effects of low doses of DA (10(-9) M). EGF was unable to do so, although markedly increased (>200%) the post-DA PRL rebound. In cells from in vivo E2-treated rats, FGF-2 increased (>50%) the PRL secretion in response to TRH, while EGF reduced responses to high doses of TRH (10(-6), 10(-5) M). In addition, FGF-2 reversed and EGF increased the inhibitory effects of DA. Both FGF-2 and EGF completely blocked the post-DA PRL rebound, in these cells. Taken together our data suggest that FGF-2 and EGF are important regulators of lactotroph responsiveness to TRH and DA in vitro, although their actions are highly dependent on estrogenic milieu.
Spuch
Carlos
C
Karolinska Institute, Division of Molecular Neurobiology, Department of Neurosciences, 17177, Stockholm, Sweden. Carlos.Spuch@ki.se
Diz-Chaves
Yolanda
Y
Pérez-Tilve
Diego
D
Mallo
Federico
F
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008954:Models, Biological; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*; D013997:Time Factors
D016222:Fibroblast Growth Factor 2; D004958:Estradiol; D013973:Thyrotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D011388:Prolactin; D004298:Dopamine