Up-regulation of cyclooxygenase-2 gene expression by chorionic gonadotropin in mucosal cells from human fallopian...

The present study investigated the regulation of cyclooxygenase-2 (COX-2) gene by human CG (hCG) in mucosal cells from human fallopian tubes. The mucosal cells contained a major [4.3 kilobase (kb)] and several minor (3.6, 2.4, and 1. 8 kb) messenger RNA (mRNA) transcripts of LH/hCG receptors and also an 80-kDa receptor protein. The receptor protein can bind 125I-hCG. Culturing mucosal cells with increasing concentrations of highly purified hCG resulted in a dose- and time-dependent increase in steady-state levels of a 4.4-kb mRNA transcript and 72-kDa protein of COX-2. Whereas hLH and hCG could mimic each other in increasing COX-2 protein levels, FSH, TSH, PRL, and isolated alpha- and beta-subunits of hCG had no effect, suggesting that the hCG effect is hormone specific and requires the conformation of native hormone. Culturing mucosal cells with increasing concentrations of hCG also resulted in a dose-dependent increase in media PGE2, levels, suggesting that the COX-2 protein increased by hCG is catalytically active. To determine the molecular mechanism of hCG action responsible for increasing the steady-state COX-2 mRNA levels, we measured the transcription rate of the COX-2 gene by nuclear run-on assay and the stability of its transcripts by an actinomycin D blocking method. The results showed that although hCG treatment had no effect on the transcription rate of COX-2 gene, it significantly increased the stability of COX-2 transcripts from 3.7 h in the control to 7.3 h after treatment. In summary, we conclude that tubal mucosal cells contain LH/hCG receptor transcripts and the receptor protein that can bind hCG. Culturing these cells with exogenous hCG and LH can up-regulate the expression of COX-2 gene by increasing the stability of transcripts. Through this up-regulation, LH and hCG may influence tubal functions that are important for early pregnancy in women.