Heparin increases prolactin and modifies the effects of fgf-2 upon prolactin accumulation in pituitary primary cultures.
We have studied the effects of heparin on prolactin accumulation in the medium from primary pituitary cultures, and whether heparin interferes with the effects of fibroblast growth factor-2 (FGF-2) on PRL regulation in vitro. In the absence of exogenous FGF-2, hepa-rin increased prolactin accumulation in the culture medium in a dose-dependent manner. FGF-2 also increased the prolactin levels of primary cells in a time- and dose-dependent manner. However, low doses of heparin reduced the effects of FGF-2, but higher doses of heparin increased the maximal FGF-2-induced prolactin secretion and ED50. In vivo estrogenization of rats resulted in the abolition of FGF-2 capability to promote prolactin release in vitro. However, heparin restored cell responsiveness to FGF-2. Our results suggest that heparin, when present in the medium, binds FGF-2, therefore reducing its ability to interact with FGF receptors in a dose-dependent manner up to a critical molar concentration, at which heparin itself starts to activate the FGF receptor, and strengthens the activation induced by its proper ligand, FGF-2. Prolactin responses to FGF-2 are blocked by estrogen pretreatment, and it is probable that this introduces lactotroph cells in the proliferative stage. In conclusion, heparin modulates PRL secretion and PRL responses to FGF-2 in vitro.
Spuch
Carlos
C
Cajal Institute, CSIC, Avd. Dr. Arce, 37, 28.002, Madrid, Spain. spuch@cajal.csic.es
Diz-Chaves
Yolanda
Y
Pérez-Tilve
Diego
D
Mallo
Federico
F
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D006493:Heparin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000502:physiology
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D011388:Prolactin; D006493:Heparin