title: Glutamine synthetase and alanine transaminase expression are decreased in livers of aged vs. young beef cows and GS can be upregulated by 17β-estradiol implants.
abstract: Aged beef cows (≥ 8 yr of age) produce calves with lower birth and weaning weights. In mammals, aging is associated with reduced hepatic expression of glutamine synthetase (GS) and alanine transaminase (ALT), thus impaired hepatic Gln-Glu cycle function. To determine if the relative protein content of GS, ALT, aspartate transaminase (AST), glutamate transporters (EAAC1, GLT-1), and their regulating protein (GTRAP3-18) differed in biopsied liver tissue of (a) aged vs. young (3 to 4 yr old) nonlactating, nongestating Angus cows (Exp. 1 and 2) and (b) aged mixed-breed cows with and without COMPUDOSE (17β-estradiol) ear implants (Exp. 3), Western blot analyses were performed. In Exp. 1, 12 young (3.62 ± 0.01 yr) and 13 aged (10.08 ± 0.42 yr) cows grazed the same mixed forage for 42 d (August-October). In Exp. 2, 12 young (3.36 ± 0.01 yr) and 12 aged (10.38 ± 0.47 yr) cows were individually fed (1.03% of BW) a corn-silage-based diet to maintain BW for 20 d. For both Exp. 1 and 2, the effect of cow age was assessed by ANOVA using the MIXED procedure of SAS. Cow BW did not change ( ≥ 0.17). Hepatic ALT (78% and 61%) and GS (52% and 71%) protein content (Exp. 1 and 2, respectively) was decreased ( ≤ 0.01), whereas GTRAP3-18 (an inhibitor of EAAC1 activity) increased ( ≤ 0.01; 170% and 136%) and AST, GLT-1, and EAAC1 contents did not differ ( ≥ 0.17) in aged vs. young cows. In Exp. 2, free concentrations (nmol/g) of Glu, Ala, Gln, Arg, and Orn in liver homogenates were determined. Aged cows tended to have less ( = 0.10) free Gln (15.0%) than young cows, whereas other AA concentrations did not differ ( 0.26). In Exp. 3, 14 aged (> 10 yr) cows were randomly allotted ( = 7) to sham or COMPUDOSE (25.7 mg of 17β-estradiol) implant treatment (TRT), and had ad libitum access to alfalfa hay for 28 d. Blood and liver biopsies were collected 14 and 28 d after implant treatment. Treatment, time after implant (DAY), and TRT × DAY effects were assessed by ANOVA using the MIXED procedure of SAS. Cow BW was not affected ( ≥ 0.96). Implant increased ( ≤ 0.02) total plasma estradiol by 220% (5.07 vs. 1.58 pg/mL) and GS protein by 300%, whereas the relative content of other proteins was not altered ( ≥ 0.16). We conclude that hepatic expression of ALT and GS are reduced in aged vs. young cows, and administration of 17β-estradiol to aged cows increases plasma estradiol and hepatic GS, but not that of other proteins that support hepatic Glu metabolism.
authors.forename: E D
authors.initials: ED
authors.lastname: Miles
authors.forename: B W
authors.initials: BW
authors.lastname: McBride
authors.forename: Y
authors.initials: Y
authors.lastname: Jia
authors.forename: S F
authors.initials: SF
authors.lastname: Liao
authors.forename: J A
authors.initials: JA
authors.lastname: Boling
authors.forename: P J
authors.initials: PJ
authors.lastname: Bridges
authors.forename: J C
authors.initials: JC
authors.lastname: Matthews
mesh_terms: D000375:Aging; D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism*; D000821:Animal Feed / Q000032:analysis; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002417:Cattle / Q000502:physiology*; D004032:Diet / Q000662:veterinary; D004063:Digestion / Q000502:physiology; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D003313:Zea mays
chemical_list: D004343:Drug Implants; D004958:Estradiol; D000410:Alanine Transaminase; D005974:Glutamate-Ammonia Ligase