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Progesterone receptors may influence fibroid growth through mitochondrial mechanism
Progesterone/progestin may play a role in the growth of fibroids by increasing mitochondrial membrane potential, according to recent study data.
The researchers utilized myometrial and fibroid tissue collected from 10 women undergoing hysterectomy for benign conditions. Five of the participants were recruited from Duke University Hospital, and tissue specimens for the other five patients were acquired from Cooperative Human Tissue Network, funded by the National Cancer Institute. All of the women were age 39 to 49 years. The ten matched tissue samples included the outer perimeter of a fibroid and bordering myometrium from the same uterus.
The researchers found that mitochondrial progesterone receptor (PR-M) and mitochondrial porin were more strongly expressed at the edge of the fibroid vs. the bordering myometrium. Mitochondrial membrane potential was increased by progestin in human telomerase reverse-transcriptase human-myometrial (hTERT-HM) cells, an effect that was not diminished by a translation inhibitor. This observation was more pronounced in hTERT-HM cells that were PR-M positive after temporary transfection.
“As fibroid cells appear to be adapted to their stiff microenvironment and thus respond less to moderate mechanical stress than other cells and are apparently resistant to apoptosis, it is possible that the energy necessary to allow for these adaptations is provided by PR-M,” the researchers wrote. “Anti-progestins have been reported to increase the apoptotic response in many, but not all, fibroid cells and tissues, raising the intriguing possibility for PR-M in altered mitochondrial function in the development of fibroids.”
The researchers used Western blot to evaluate protein levels of progesterone receptors A, B and PR-M, and mitochondrial porin in the edge of the [fibroid] and nearby [myometrium]. They analyzed progestin-induced mitochondrial membrane potential in non-transfected and transfected hTERT-HM cells.
Disclosure: The researchers report no relevant financial disclosures.