15-Lipoxygenase products stimulate prolactin secretion from a cloned strain of rat pituitary cells

Arachidonic acid and its lipoxygenase products may contribute to the process of prolactin (PRL) release. In the present study we investigate the role of 15-hydroperoxyeicosatetraenoic acid (15-HPETE) and 15-hydroxyeicosatetraenoic acid (15-HETE) on PRL secretion from GH3 cells. The incubation of GH3 cells with the lipoxygenase product 15-HETE significantly increased PRL release in a concentration-dependent manner. Nordihydroguaiaretic acid (NDGA), which reduces the production of arachidonate metabolites via the lipoxygenase pathway, also reduced basal and TRH or arachidonic-acid-stimulated-PRL release. The inhibitory effect of NDGA on PRL release could be overcome by the addition of 15-HETE. The time course curve of PRL release from cells challenged by 15-HETE had the same profile as that of cells stimulated by TRH. The stimulating effect of 15-HPETE (ED50 = 0.7 x 10(-9) M), which is the direct precursor of 15-HETE, on PRL release was greater than TRH or 15-HETE (ED50 = 6.5 x 10(-9) M). Furthermore 15-HPETE and 15-HETE seemed to affect the release of newly synthesized PRL. These data indicate that 15-HETE and 15-HPETE could be important intracellular components in the control of PRL secretion and may account for at least a part of arachidonate-induced PRL release from GH3.