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

Abstract

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.

Extragonadal Luteinizing Hormone Receptors in the Reproductive Tract of Domestic Animals1

“…Treatment of human cervical tissue minces with hCG resulted in a significant increase in cAMP levels, with a concomitant decline in PGHS-2 protein. It is interesting that in the human, LH induces PGHS-2 in the oviduct [6] and uterus [42] but inhibits PGHS-2 in the cervix [70]. The PGHS-2 response to LH in the human cervix was opposite that reported for the cow cervix [69], which may reflect a species difference in the role of LH in cervical functions.…”

“…Estradiol benzoate increased the number of LH-binding sites in oviduct 24-72 h after injection compared to control gilts treated with corn oil [10]. A direct influence of estradiol on the LHR was shown when the LHR was up-regulated by estradiol in cultured human oviductal epithelial cells [6]. Tubal-receptor concentrations vary during the menstrual cycle in women, and the fallopian tubes contain more LHR during the secretory phase than during the proliferative phase [5].…”

“…Luteinizing hormone receptors have been demonstrated in human [5,6], bovine [7,8], porcine [9][10][11][12], turkey (infundibulum) [13], and mouse [14] fallopian tubes (Table 1). Lei et al.…”

“…The presence of oviductal LHR and/ or activation by LH has been demonstrated in several species. The LHR activation resulted in up-regulation of PG endoperoxidase H synthase (PGHS)-1 and -2 [5,6], synthesis of PGE 2 and PGF 2␣ [5,6,16,17], 5-lipoxygenase [5], oviductal glycoprotein [7,8], and endothelin-1 [16,17], which have been shown to play an important role in various oviductal functions.…”

Gonadal and nongonadal FSHR and LHR dysfunction during lipopolysaccharide induced failure of blastocyst implantation in mouse

“…LHR is important in endometrium decidualization, implantation of embryos [9], regulation of uterine blood flow and maintenance of early pregnancy [19]. LH was shown to stimulate directly the uterine growth in mouse [15,34].…”