title: Heparin increases prolactin and modifies the effects of fgf-2 upon prolactin accumulation in pituitary primary cultures.
abstract: 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.
authors.affiliation: Cajal Institute, CSIC, Avd. Dr. Arce, 37, 28.002, Madrid, Spain. spuch@cajal.csic.es
authors.forename: Carlos
authors.initials: C
authors.lastname: Spuch
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Diz-Chaves
authors.forename: Diego
authors.initials: D
authors.lastname: Pérez-Tilve
authors.forename: Federico
authors.initials: F
authors.lastname: Mallo
mesh_terms: 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
chemical_list: D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D011388:Prolactin; D006493:Heparin