Progesterone increases skeletal muscle mitochondrial H2O2 emission in nonmenopausal women

摘要

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 H2O2 emission (mEH2O2) and insulin resistance. To determine whether serum levels of P4 and/or E2 are related to mitochondrial function, mEH2O2 and respiratory O2 flux (Jo2) 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 mEH2O2 was more than 50% greater in the IR vs. IS women (P < 0.05). Interestingly, serum P4 correlated positively with succinate-supported mEH2O2 (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 Jo2, supported by multisubstrate combination (P < 0.01). However, E2 alone or in combination with P4 had no effect on Jo2. In contrast, during state 4 respiration, supported by succinate and glycerophosphate, mEH2O2 was increased with P4 alone or in combination with E2 (P < 0.01). The results suggest that 1) P4 increases mEH2O2 with or without E2; 2) P4 alone inhibits Jo2 but not when E2 is present; and 3) P4 is related to the mEH2O2 previously linked to skeletal muscle insulin resistance.