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Progesterone increases skeletal muscle mitochondrial H2O2 emission in nonmenopausal women
Journal article   Open access

Progesterone increases skeletal muscle mitochondrial H2O2 emission in nonmenopausal women

Daniel A Kane, Chien-Te Lin, Ethan J Anderson, Hyo-Bum Kwak, Julie H Cox, Patricia M Brophy, Robert C Hickner, P. Darrell Neufer and Ronald N Cortright
American journal of physiology: endocrinology and metabolism, Vol.300(3), pp.E528-E535
03/2011
DOI: 10.1152/ajpendo.00389.2010
PMCID: PMC3064007
PMID: 21189359
url
https://doi.org/10.1152/ajpendo.00389.2010View
Published (Version of record) Open Access

Abstract

The luteal phase of the female menstrual cycle is associated with both 1 ) elevated serum progesterone (P4) and estradiol (E2), and 2 ) reduced insulin sensitivity. Recently, we demonstrated a link between skeletal muscle mitochondrial H 2 O 2 emission (mE H2O2 ) and insulin resistance. To determine whether serum levels of P4 and/or E 2 are related to mitochondrial function, mE H2O2 and respiratory O 2 flux ( J o 2 ) were measured in permeabilized myofibers from insulin-sensitive (IS, n = 24) and -resistant (IR, n = 8) nonmenopausal women (IR = HOMA-IR > 3.6). Succinate-supported mE H2O2 was more than 50% greater in the IR vs. IS women ( P < 0.05). Interestingly, serum P4 correlated positively with succinate-supported mE H2O2 ( r = 0. 53, P < 0.01). To determine whether P4 or E2 directly affect mitochondrial function, saponin-permeabilized vastus lateralis myofibers biopsied from five nonmenopausal women in the early follicular phase were incubated in P4 (60 nM), E2 (1.4 nM), or both. P4 alone inhibited state 3 J o 2 , supported by multisubstrate combination ( P < 0.01). However, E2 alone or in combination with P4 had no effect on J o 2 . In contrast, during state 4 respiration, supported by succinate and glycerophosphate, mE H2O2 was increased with P4 alone or in combination with E2 ( P < 0.01). The results suggest that 1 ) P4 increases mE H2O2 with or without E2; 2 ) P4 alone inhibits J o 2 but not when E2 is present; and 3 ) P4 is related to the mE H2O2 previously linked to skeletal muscle insulin resistance.
sex hormones insulin resistance oxidative stress estradiol

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