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Fig. 3 | Military Medical Research

Fig. 3

From: Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

Fig. 3

Interplay between sex hormones, mitochondrial function, and endothelial function. a All steroid hormones are made from cholesterol, which has two potential sources from either de novo synthesis by using acetate or importing of circulating high density lipoproteins (in rodent cells) and low-density lipoproteins (in human steroidogenic cells). Intracellular free cholesterol can be re-esterified and stored in lipid droplets or reach the outer mitochondrial membrane then move into inner mitochondrial membrane where it can be converted to pregnenolone as substrate for steroidogenesis. Mitochondrial integrity is important in the biosynthesis of sex steroid hormones by modulating enzymes for steroidogenesis and by maintaining cells that produce these hormones. After secretion, circulating estrogen (E) form a complex with estrogen receptor (ER) to exert its intracellular function through both genomic and non-genomic actions. For example, through modulating the gene of transcription factors, such as peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) and nuclear respiratory factor-1 (NRF1) to control transcription of mitochondrial encoded genes or alter mitochondrial function by modification of mitochondrial proteins. b Estrogen is a primary target of endothelial nitric oxide synthase (eNOS), which converts arginine into citrulline along with the formation of nitric oxide (NO) in the process. Under normal physiological conditions, NO is the predominate product exhibiting positive cardiovascular effects. Following aging, estrogen deprivation is accompanied by a reduced eNOS activity, resulting in an accumulation of reactive oxygen species, thereby scavenging NO to reduce its bioavailability. As a result, stress related protein modification accelerates age-related arterial stiffening and endothelium dysfunction. SOD superoxide dismutase

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