Arachidonic Acid Metabolism and Prolactin Secretion in vitro: A Possible Role for the Lipoxygenase Products

Abstract

This study was designed to investigate basal and thyrotropin-releasing hormone (TRH)-stimulated prolactin release in the presence of agents that influence arachidonic acid metabolism. Agents that decrease its production by blocking phospholipase A2 activity, i.e., quinacrine and 4-bromophenacylbromide, significantly decreased prolactin secretion from anterior pituitary glands in vitro and from dispersed pituitary cells in a perifusion column. Phospholipase A2 and phorbol myristate acetate, substances that increase intracellular concentrations of arachidonic acid, markedly stimulated prolactin release by dispersed pituitary cells and by anterior pituitary glands incubated in vitro. The involvement in prolactin secretion of arachidonic acid metabolic products produced via the lipoxygenase pathway was investigated indirectly using nordihydroguaiaretic acid (NDGA), a specific inhibitor of this enzyme. NDGA progressively (dose-related) inhibited the release of prolactin in vitro and blocked the stimulating effect of 50 nM TRH on prolactin release from hemipituitary glands. Indomethacin, a specific inhibitor of the cycloxygenase pathway, had no significant effect on basal and TRH-stimulated prolactin release. The results suggest that arachidonic acid metabolism is involved in basal and TRH-stimulated prolactin secretion and that lipoxygenase pathway products are at least partially responsible for these effects.

Effects of Intra-ovarian Bursal Injection of Eicosanoid Synthesis Inhibitors on Luteal Function in Immature Pseudopregnant Rats

“…The effect of systemically injected inhibitors on luteal activity may be mediated by substances other than eicosanoids. There are some reports that the secretion of LH or prolactin, which is relevant to rat luteal function, is modulated by arachidonate or eicosanoids in the rat pituitary [28][29][30][31].…”

Polyphosphoinositide hydrolysis by phospholipase C is accelerated by thyrotropin releasing hormone (TRH) in clonal rat pituitary cells (GH3 cells)

“…PA, increased in steady state in the presence of TRH [8], is a Ca2+ ionophore [29] and a main source for the precursor arachidonic acid utilized in prostaglandin and leukotriene synthesis [30,31]. Both protein kinase C and arachidonic acid metabolism are also regulated by Ca2+ [25,26,29] such that [Ca2'], could modulate these processes in the stimulated cells.…”

Leukotriene C4 as a mediator of luteinizing hormone release from rat anterior pituitary cells.

“…The largest amounts of LTC4 were produced in the hypothalamus and the median eminence. This is of interest since a role for lipoxygenase products in anterior pituitary function has been suggested (3,4). The present report demonstrates that LTC4 released luteinizing hormone (LH) but not growth hormone (GH) from dispersed rat anterior pituitary cells after 0.5 hr in culture.…”