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, heparin 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.