Society for Endocrinology - a world-leading authority on hormones


Endocrinologist 150 Cover (Small)
Issue 150 Winter 2023

Endocrinologist > Winter 2023 > Hot topics


INHIBITING MITOCHONDRIAL FISSION AND PROTEIN KINASE R IMPROVES PROGESTERONE IN PLACENTAL STRESS

| Hot topics



The placenta is essential for human existence, yet remains one of the biggest physiological mysteries. Researchers have attempted to understand the molecular functioning of placental tissue for decades and have struggled to do so, particularly when it comes to shining a spotlight on changes that may proceed disease states and, ultimately, the successful growth of a fetus.

This new research study by Kolaç begins to unravel the fundamental mechanism of placental cell stress, with the goal of improving the release of a key steroid hormone, progesterone. The study’s overall aim was to determine the roles of the mitochondrial division inhibitor mdivi1 and the protein kinase R (PKR) inhibitor 2-aminopurine in countering the decrease in progesterone synthesis which is seen as a result of lipopolysaccharide (LPS)- and polyinosinic:polycytidylic acid (Poly I:C)-induced stress in the mitochondria of cultured BeWo trophoblast cells.

This study clearly demonstrates that the upregulation of mitochondrial fission under LPS- and Poly I:C-induced stress is accompanied by a downregulation of progesterone biosynthesis in the placental trophoblast. Furthermore, it suggests that both mdivi1 treatment and inhibition of PKR (a kinase located at the intersection of many signalling pathways) is effective in elevating progesterone levels.

The negative impact of inflammatory stress-induced mitochondrial fission on progesterone synthesis may lead to complications in placental function and the progression of pregnancy, and may be an underlying molecular change in many pregnancy-related pathologies. This study opens up thoughts of whether big stress events are the trigger, or whether smaller stress insults over a longer period may be influential. Regardless, effects on the production of progesterone have huge ramifications for the control of the maternal immune system and placental growth. If this molecular stress is the cause, we can begin to incorporate therapeutic options for pregnancy complications, which have long been left wanting.

Read the full article in Journal of Molecular Endocrinology 71 e230059




This Issue:

Winter 2023

Winter 2023

The Endocrinologist

...

Autumn 2024

Autumn 2024