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

Abstract

This study demonstrates that leukotriene C4, at concentrations in the picomolar range, released luteinizing hormone (LH) but not growth hormone (GH) from dispersed rat anterior pituitary cells. Leukotriene B4, another lipoxygenase pathway product of arachidonic acid, had no effect on LH or GH release. The stimulatory effect of leukotriene C4 could be seen after 0.5 but not after 3 hr of incubation. This was in contrast to the dose-dependent LH-releasing hormone (LHRH)-induced LH release that was not measurable after 0.5 hr but was fully established after incubation for 3 hr. Furthermore, the LH-releasing ability of leukotriene C4 was blocked in the presence of high doses of LHRH. The immunohistochemical analysis revealed leukotriene C4-immunoreactive fibers at all levels of the median eminence, mainly in the lateral parts. These fibers exhibited a marked overlap distribution with LHRH-immunoreactive fibers and elution-restaining experiments revealed identity of at least a large proportion of the leukotriene C4-and LHRH-immunoreactive fibers. Furthermore, cell bodies in the preoptic area contained both leukotriene C4-and LHRH-like immunoreactivities, suggesng localization of these two compounds in the same neurons.The leukotrienes (LTs) are compounds with biological effects related to anaphylaxis and inflammation. LT formation is initiated by 5-lipoxygenation of arachidonic acid to 5 (S)-hydroperoxyicosatetraenoic acid, which is further transformed into an unstable epoxide, LTA4. Enzymatic addition of glutathione to this intermediate leads to formation of LTC4, which can be further metabolized to LTD4 and LTE4. Alternatively, LTA4 is enzymatically hydrolyzed to the dihydroxy acid LTB4 (see ref. 1 for review). Formation of LTC4, LTD4, and LTE4 in the rat brain has been described recently (2,27,28). 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.

Characterization of the Human Cysteinyl Leukotriene 2 Receptor

“…2 Tissues other than myeloid cell containing organs, such as the spleen and lymph nodes, that showed expression of the mRNA for the CysLT 2 receptor included regions of the central nervous system, the adrenal gland, and the heart. The synthesis and activities of cysteinyl leukotrienes in the brain of various animal species has been well documented (21)(22)(23). Studies on expression of both the CysLT 1 and CysLT 2 receptors in the central nervous system are under way in our laboratories.…”

Stimulation of progesterone and prostaglandin E2 production by lipoxygenase metabolites of arachidonic acid

“…The 5-lipoxygenase pathway is of special interest because 5-HPETE and 5-HETE can be rapidly converted to leukotrienes, which are presumably the most active of the lipoxygenase metabolites of AA [ 13,141. It has been reported that leukotrienes are effective stimulators of LH release from dispersed rat anterior pituitary cells [9,10,15]. In view of the present demonstration of stimulatory effects of 5-HETE and 5-HPETE on P and PGE2 production, the role of leukotrienes on ovarian cell function warrants further investigation.…”

Interpretation of dose-response curves for luteinizing hormone release by gonadotropin-releasing hormone, related peptides, and leukotriene C4 according to a hormone/receptor/effector model.

“…Two effectors might, however, result in generation of two different second messengers. Garcfa-Sainz and colleagues (14,15) [5] [HER] [HER-E2] Conservation of mass requires that Ho = H + H'R + H R E1 + H-R-E2 + 2H*R El R H + 2H-R-E2-R-H, [6] Ro= R + HER + HlR-El + HR'E2 + 2H R E1 R H + 2H*R-E2-R-H, [7] Elo = E1 + H-R-E1 + H-R*ElgR-H, [8] E2o = E2 + H-R-E2 + H-R*E2*R-H, [9] where H., R, E1o, and E20 are the total amounts (per unit volume) of ligand added, of receptor, of effector 1, and of effector 2, respectively. In Eqs.…”

“…Leukotriene C4 (LTC4) has recently also been shown to stimulate LH release by anterior pituitary cells in primary culture (5). LH secretion is significantly increased with 1 fM LTC4, reaches a maximum at about 1 pM, and then decreases to near-basal levels as LTC4 concentration increases to 0.01…”