Apo A-I metabolism in cynomolgus monkeys: male-female differences.
Female cynomolgus monkeys have significantly higher plasma apo A-I concentrations than males (P = 0.04) and are able to maintain higher levels than the males even after consuming a high-cholesterol diet that severely depresses the apo A-I concentration in primates (P less than 0.05). The mechanism responsible for this difference was investigated by comparing apo A-I turnover (synthesis and catabolism) in males and females consuming monkey chow and in a separate group of males and females that had consumed the high-cholesterol diet for several weeks. The average length of time an apo A-I molecule remained in the plasma compartment of chow-fed monkeys was 2.62 days but decreased to 1.52 days (P less than 0.01) in animals fed the HC diet. There were no male-female differences in the residence times. The absolute turnover rate (mg/day) of apo A-I was not statistically affected by diet or sex; however, the females were substantially smaller than the males (3.8 vs. 4.8 kg; P less than 0.01) and their plasma volumes were significantly smaller than those of the males, even after correction for differences in body wt. (32.6 vs. 37.0 ml/kg, respectively; P less than 0.01). Taken together, the data indicate that females cynomolgus monkeys have higher apo A-I synthesis rates than males of comparable plasma volume (P = 0.03), which we would propose accounts for the higher plasma apo A-I concentrations evident in females.
Melchior
G W
GW
Upjohn Company, Kalamazoo, MI 49001.
Castle
C K
CK
Vidmar
T J
TJ
Polites
H G
HG
Marotti
K R
KR
D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood*; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006937:Hypercholesterolemia / Q000097:blood; D007700:Kinetics; D008252:Macaca fascicularis; D008297:Male; D012727:Sex Characteristics
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D002791:Cholesterol, Dietary