title: Rapid stimulation of human chorionic gonadotropin secretion by interleukin-1 beta from perifused first trimester trophoblast.
abstract: Placental trophoblast has been implicated as a major source of interleukin-1 beta (IL-1 beta), a cytokine that mediates immunological responses in the body. This study evaluated the effect of IL-1 beta on hCG secretion from 8- to 12-week-old placental trophoblast. Physically dissociated trophoblast cells collected from multiple placentae were cultured on carrier beads and loaded into chambers in a perifusion system. Medium was perifused through the chambers, and effluent was collected and assayed for hCG. Basal hCG secretion was not dependent on exogenous IL-1 beta or GnRH, but varied between mixed placental preparations and increased with duration of culture. Therefore, hCG secretion was expressed as a percentage of mean basal hCG secretion for any given chamber. IL-1 beta (10(-9) M) stimulated a rapid and transient hCG secretory response. hCG release increased by approximately 150% (P less than 0.05; n = 5) in response to the cytokine, but lower concentrations (10(-10) and 10(-11) M) were ineffective (P greater than 0.05; n = 3 each). GnRH stimulated hCG secretion by approximately 80% (P less than 0.05; n = 6). The hCG secretory profiles in response to IL-1 beta and GnRH were similar. Combined treatment with equimolar (10(-9) M) IL-1 beta and GnRH increased hCG secretion by approximately 150% (P less than 0.05; n = 5), stimulating hCG secretion as effectively as either hormone alone (P greater than 0.05). The stimulatory effect of GnRH on hCG secretion was blocked by the concomitant presence of a GnRH antagonist, Nal-Glu-GnRH (P less than 0.05; n = 5). However, simultaneous treatment with IL-1 beta and Nal-Glu-GnRH did not affect IL-1 beta-stimulated hCG secretion (100.5 +/- 3.6 vs. 162.9 +/- 10.2%; P less than 0.05; n = 7). The data suggest that IL-1 beta and GnRH stimulated a near-maximal physiological hCG secretory response, possibly through different receptor types. Alternatively, these two hormones may share a common signal transduction pathway, or IL-1 beta may influence a step distal to the coupling of GnRH to its receptor in the placental trophoblast.
authors.affiliation: Department of Obstetrics and Gynecology, Grace Hospital, University of British Columbia, Vancouver, Canada.
authors.forename: G L
authors.initials: GL
authors.lastname: Steele
authors.forename: W D
authors.initials: WD
authors.lastname: Currie
authors.forename: E H
authors.initials: EH
authors.lastname: Leung
authors.forename: B H
authors.initials: BH
authors.lastname: Yuen
authors.forename: P C
authors.initials: PC
authors.lastname: Leung
mesh_terms: D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D010477:Perfusion; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D013997:Time Factors; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D007375:Interleukin-1; D007987:Gonadotropin-Releasing Hormone