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12-Lipoxygenase activity in human uterine cervix
S Flatman1, A Morgan, R G McDonald-Gibson
1Department of Biochemistry, Uxbridge, Middlesex, U.K.
Summary
This study investigated 12-lipoxygenase activity in human uterine tissues. Enzyme activity, measured via 12-hydroxyeicosatetraenoic acid production, was lower in post-menopausal women and varied significantly between cervical samples.
Area of Science:
- Biochemistry
- Reproductive Biology
- Human Physiology
Background:
- Arachidonic acid metabolism plays a crucial role in various physiological processes.
- Eicosanoids, derived from arachidonic acid, are implicated in reproductive tissue function.
- 12-lipoxygenase (12-LO) pathway enzymes and their products, such as 12-hydroxyeicosatetraenoic acid (12-HETE), are present in the female reproductive tract.
Purpose of the Study:
- To investigate the presence and activity of 12-lipoxygenase in human uterine cervix and endometrium.
- To characterize the products of arachidonic acid metabolism in these tissues.
- To explore potential variations in 12-lipoxygenase activity related to menopausal status and endometrial histology.
Main Methods:
- Incubation of human uterine cervix and endometrium homogenates with [1-14C]arachidonate.
- Analysis of metabolic products using radio-thin-layer chromatography (radio-TLC).
- Assessment of enzyme activity using specific inhibitors like indomethacin and nordihydroguaiaretic acid, and the effect of glutathione.
Main Results:
- A major product identified as 12-hydroxyeicosatetraenoic acid (12-HETE) was detected.
- Polar metabolites were also observed, sensitive to nordihydroguaiaretic acid but not indomethacin.
- Glutathione addition increased 12-HETE production while decreasing polar metabolites.
- Significant variability in 12-lipoxygenase activity was noted across cervical samples.
- Enzyme activity was comparable between proliferative and secretory endometrium but significantly lower in post-menopausal versus pre-menopausal patients.
Conclusions:
- Human uterine cervix and endometrium possess 12-lipoxygenase activity, producing 12-HETE and other metabolites.
- The activity of this pathway shows significant inter-individual variation in the cervix.
- 12-lipoxygenase activity in the cervix is diminished in post-menopausal women compared to pre-menopausal women.
- Endometrial histology (proliferative vs. secretory) did not significantly impact cervical 12-lipoxygenase activity.