title: Progesterone increases skeletal muscle mitochondrial H2O2 emission in nonmenopausal women.
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 (Jo(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 Jo(2), supported by multisubstrate combination (P < 0.01). However, E2 alone or in combination with P4 had no effect on Jo(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 Jo(2) but not when E2 is present; and 3) P4 is related to the mE(H2O2) previously linked to skeletal muscle insulin resistance.
authors.affiliation: The Human Performance Laboratory, East Carolina University, Greenville, NC 27858, USA. dkane@stfx.ca
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Kane
authors.forename: Chien-Te
authors.initials: CT
authors.lastname: Lin
authors.forename: Ethan J
authors.initials: EJ
authors.lastname: Anderson
authors.forename: Hyo-Bum
authors.initials: HB
authors.lastname: Kwak
authors.forename: Julie H
authors.initials: JH
authors.lastname: Cox
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Brophy
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hickner
authors.forename: P Darrell
authors.initials: PD
authors.lastname: Neufer
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Cortright
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005498:Follicular Phase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D007700:Kinetics; D008183:Luteal Phase / Q000378:metabolism; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D055815:Young Adult
chemical_list: D011374:Progesterone; D004958:Estradiol; D006861:Hydrogen Peroxide