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It is well known that the smooth muscle of the human myometrium is a target for the steroid hormones progesterone (P4) and estrogen. Progesterone is believed to participate in the maintenance of pregnancy, while estrogen is possibly involved in the process of parturition by promoting cervical dilatation. We examined the combined effects of P4 and 17beta-estradiol (E2) on components of signalling pathways in human myometrial cells in vitro by immunoblotting. Long-term treatment of myometrial cells with a series of concentrations of P4 and E2 in combination caused a change in the phosphorylation status of p42/44 mitogen-activated protein kinase and of c-Jun N-terminal kinase (SAPK/JNK). P4 and E2 caused a decrease in protein expression of Gqalpha, Gzalpha, Gi1/2alpha and, to a lesser extent, G0alpha. The two steroids caused a decrease in the expression of the two small GSalpha isoforms. Cyclo-oxygenase-2 expression was increased by 2.5-fold after steroid treatment, while proliferating cell nuclear antigen expression levels remained unchanged. These observations show that the combination of P4 and E2 influences intracellular and membrane-bound components of signal transduction pathways in human myometrial cells. The implications of the two steroid hormones on intracellular signalling pathways in the human myometrium merits further investigation.

Type

Journal article

Journal

Mol Hum Reprod

Publication Date

07/2002

Volume

8

Pages

597 - 605

Keywords

Cyclooxygenase 2, Estradiol, Estrogens, Female, GTP-Binding Proteins, Humans, Isoenzymes, JNK Mitogen-Activated Protein Kinases, MAP Kinase Kinase 4, Membrane Proteins, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Myometrium, Phosphorylation, Progesterone, Prostaglandin-Endoperoxide Synthases, Signal Transduction