Carlos A. Valdenegro

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

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.

Effect of Antiestrogens on Pituitary Prolactin Production in Normal and Pituitary Tumor-Bearing Rats

Administration of the antiestrogen tamoxifen to normal Buffalo female rats caused a 45% reduction (p less than 0.01) in 3H-prolactin synthesis and release in vitro. Radioimmunoassayable prolactin in incubated glands and medium also decreased significantly. Similar results were observed in Wistar-Furth animals except for in vitro radioimmunoassayable prolactin, which decreased less markedly (by 33%, p less than 0.01). Serum prolactin concentration in treated rats was unchanged. Tamoxifen did not affect the extremely high serum prolactin concentration in rats bearing mammotropic tumors. It further reduced in vitro synthesis of radioactive prolactin but not of the radioimmunoassayable hormone. No interaction between antiestrogens and the dopamine agonist bromocriptine was observed. These observations suggest that the nonsteroidal antiestrogens decrease the synthesis of prolactin but have little effect on release of the hormone. Tamoxifen inhibits growth of transplantable mammotropic tumors MtTW15 and 7315a potently without altering tumor prolactin production. In vivo treatment of adult female rats with tamoxifen did not affect in vitro synthesis and release of radioactive growth hormone, but reversed the elevated growth hormone production of rats bearing 7315a tumors.

Arachidonic acid metabolism and thyrotropin secretion in vitro

We investigated the role of arachidonic acid and certain of its metabolic products in the control of thyrotropin (TSH) secretion in vitro. Phospholipase A2 and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), which increase the intracellular availability of arachidonic acid, potently stimulated TSH release from anterior pituitary cells continuously perifused in columns and from hemipituitary glands in vitro. The effect was dose-dependent and reversible. Conversely, quinacrine (50 microM), an inhibitor of phospholipase A2 activity, inhibited basal and stimulated TSH release from pituitary cells perifused in columns. Exogenous arachidonic acid (1-100 microM) did not produce any significant effect on TSH release from hemipituitary glands in vitro. Nordihydroguaiaretic acid (NDGA), a specific inhibitor of the lipoxygenase pathway, dose-dependently inhibited basal TSH release from anterior pituitary glands incubated in vitro. Moreover, 50 microM NDGA antagonized the stimulatory effect of thyrotropin releasing hormone (TRH), phospholipase A2 and PMA on TSH release. BW755c, another lipoxygenase inhibitor, also inhibited TRH-stimulated TSH secretion. In contrast, 10-100 microM indomethacin, a potent blocker of the cyclooxygenase pathway, did not significantly modify either basal or TRH-stimulated TSH secretion from hemipituitary glands in vitro. These data suggest that arachidonic acid metabolism is involved in TSH secretion in vitro, although incubation of pituitary glands with the fatty acid did not apparently modify in our conditions basal TSH secretion. The eventual effect of arachidonate appears to be at least partially due to the action of its lipoxygenase pathway products.

Anterior pituitary enzyme activities and prolactin secretion in male rats treated with psychotropic drugs.

Summary Psychotropic dopamine antagonists primarily stimulate prolactin release, and their subchronic administration does not influence the water-soluble protein concentration, the hexosemonophosphate shunt, and anaerobic glycolytic, oxidative, or lysosomal activity of the lactotrophs.