JURKAT CELL PROLIFERATIVE ACTIVITY IS INCREASED BY LUTEINIZING-HORMONE-RELEASING HORMONE

Jurkat cells were used to study the immunomodulatory role of luteinizi ng hormone-releasing hormone (LHRH) in immune cells. The Jurkat cell, a human mature leukemic cell line, phenotypically resembles resting hu man T lymphocytes and has been widely used to study T cell physiology. The data from this study demonstrate that the Jurkat cell concentrati on of immunoreactive LHRH was 210 +/- 36 pg/10(6) cells and that of pr oLHRH was 188 +/- 27 pg/10(6) cells (means +/- S.E.M.). The authentici ty of this LHRH immunoreactivity is documented in two ways. First, bot h Jurkat LHRH and proLHRH immunoreactivity demonstrate dilutional para llelism with hypothalamic LHRH and proLHRH. Second, Jurkat lysates sho w LHRH bioactivity by releasing luteinizing hormone from rat anterior pituitary cells in culture. The presence of substantial amounts of LHR H in medium in which Jurkat cells were cultured for 72 h indicated tha t LHRH can be released from the cells. Using specific primers to exons 2 and 4 of the LHRH gene, we have found that Jurkat cells (like human T cells) express LHRH mRNA. The LHRH agonist, des-Gly(10),D-Trp(6)-LH RH ethylamide, significantly increases the proliferative activity of J urkat cells, as assessed by tritiated thymidine incorporation, from 15 980 +/- 1491 c.p.m. in controls to 28 934 +/- 3395, 30 457 +/- 3861 (P = 0.05 vs control) or 35 299 +/- 5586 c.p.m. (P<001 vs control) with 10(-11), 10(-9) or 10(-7) M agonist respectively. LHRH antagonist, [D- pGlu(1),D-Phe(2),D-Trp(3,6)]-LHRH, at a concentration of 10(-8) M decr eases Jurkat cell proliferative activity from 17145 +/- 526 c.p.m. in control medium to 10653 +/- 1323 c.p.m. (P=0.05). Go-incubation with t he LHRH antagonist completely inhibits the proliferative stimulation i nduced by the LHRH agonist. Furthermore, applying monoclonal LHRH anti body to Jurkat cells inhibits the cell proliferative activity assessed by tritiated thymidine incorporation from 19 900 +/- 2675 c.p.m. in c ontrols to 15 680 +/- 2254, 15 792 +/- 1854 and 9700 +/- 908 c.p.m. in media with 1:40, 1:20 and 1:10 dilution of purified antibody respecti vely (P<0.01, 1:10 dilution compared wit h control). In addition, the cAMP level in LHRH-stimulated Jurkat cells is decreased to 74, 27 and 57% of control levels after 15, 30 and 45 min respectively of exposure to 10(-7) M LHRH agonist. In summary, Jurkat cells produce, process a nd release immunoreactive and bioactive LHRH, as do normal human T cel ls. Endogenous and exogenous LHRH increase Jurkat cell proliferative a ctivity, and cAMP may be involved in LHRH-induced Jurkat cell prolifer ation. The Jurkat cell may be a useful model with which to study the r ole of LHRH in human T cell function.