Stress triggers mitochondrial biogenesis to preserve steroidogenesis in Leydig cells

Abstract

Adaptability to stress is a fundamental prerequisite for survival. Mitochondria are a key component of the stress response in all cells. For steroid-hormones-producing cells, including also Leydig cells of testes, the mitochondria are a key control point for the steroid biosynthesis and regulation. However, the mitochondrial biogenesis in steroidogenic cells has never been explored. Here we show that increased mitochondrial biogenesis is the adaptive response of testosterone-producing Leydig cells from stressed rats. All markers of mitochondrial biogenesis together with transcription factors and related kinases are up-regulated in Leydig cells from rats exposed to repeated psychophysical stress. This is followed with increased mitochondrial mass. The expression of PGC1, master regulator of mitochondrial biogenesis and integrator of environmental signals, is stimulated by cAMP-PRKA, cGMP, and β-adrenergic receptors. Accordingly, stress-triggered mitochondrial biogenesis represents an adaptive mechanism and does not only correlate with but also is an essential for testosterone production, being both events depend on the same regulators. Here we propose that all events induced by acute stress, the most common stress in human society, provoke adaptive response of testosterone-producing Leydig cells and activate PGC1, a protein required to make new mitochondria but also protector against the oxidative damage. Given the importance of mitochondria for steroid hormones production and stress response, as well as the role of steroid hormones in stress response and metabolic syndrome, we anticipate our result to be a starting point for more investigations since stress is a constant factor in life and has become one of the most significant health problems in modern societies.

Psychological Stress and Mitochondria: A Systematic Review

“…Acute stress may damage mitochondrial structure within hours and enhance certain aspects of their function. Several studies investigating mitochondrial morphology and ultrastructure by electron microscopy reported acute mitochondrial damage with stress ( 53 , 55 , 57 , 70 , 74 ), whereas other showed increased size of mitochondria with chronic stress ( 63 ), possibly reflecting an increase in biogenesis. Although some studies reported gross disruption in mitochondria indicative of dysfunction and pathological swelling, the lack of quantitative analysis of mitochondrial shape and morphology precludes conclusions regarding the effects of stress on mitochondrial shape.…”

Reduced spermatozoa functionality during stress is the consequence of adrenergic-mediated disturbance of mitochondrial dynamics markers

“…In the search for the possible mechanism(s) causing the reduced spermatozoa functionality during/after psychological stress, two approaches (in vivo and ex vivo) were applied. The in vivo approach was design to mimic the situations in the human population exposed to acute as well as repeated psychological stress, the most common stress in human society, by using the immobilization of the adult male rat 16,17 . The ex vivo approach was performed on epididymal spermatozoa isolated from the undisturbed adult male rats and exposed to stress hormones and the agonists/antagonists of their receptors.…”

“…Most of the methods used in the present study were previously reported by our group in more detail (for all references please see 16,17,64 as well as in Supplemental Material and Methods, and are outlined briefly here.…”

“…as decrease of circulating testosterone in males [14][15][16][17] . At the cellular level, stressors can strongly disturb cellular homeostasis and some of the effects could be inherited.…”

Apigenin inhibits growth of the Plasmodium berghei and disrupts some metabolic pathways in mice

“…Some studies indicate that consumption of dietary flavonoids like apigenin may likewise alter the metabolite profile of steroids through modulation of the biosynthesis and metabolism of steroid hormones or via CYP substrates (Dai, Jacobson, Robinson, & Friedman, ; Ibrahim & Abul‐Hajj, ).Given the importance of steroid hormones in stress response, as well as, the role of mitochondria in steroid hormones production(Piantadosi & Suliman, ), it is suggested that acute stress induced by apigenin resulted in ROS (reactive oxygen species) production and disturbed activity of steroidogenic and antioxidative enzymes. The stress induced distributions activate many signaling pathways in order to trigger mitochondrial biogenesis and prevent loss of basal steroidogenic function (Gak et al, ).Our finding is in line with that of previous studies which showed that apigenin can disrupt the endocrine system and, therefore, suggest caution in using apigenin to achieve the therapeutic goals.…”