RAPID STIMULATION OF HUMAN CHORIONIC-GONADOTROPIN SECRETION BY INTERLEUKIN-1-BETA FROM PERIFUSED 1ST TRIMESTER TROPHOBLAST

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 < 0.05; n = 5) in response to the cytokine, but lower concentrations (10(-10) and 10(-11) m) were ineffective (P > 0.05; n = 3 each). GnRH stimulated hCG secretion by approximately 80% (P < 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 < 0.05; n = 5), stimulating hCG secretion as effectively as either hormone alone (P > 0.05). The stimulatory effect of GnRH on hCG secretion was blocked by the concomitant presence of a GnRH antagonist, Nal-Glu-GnRH (P < 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 < 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.