Impact of female sex hormones on liver tissue lactic acidosis during ischemia.
BACKGROUND
Lower liver transplant success is observed when the donor is female. Intracellular acidosis during ischemia is proposed to contribute to the injury sustained by the transplanted organ and its role in livers obtained from nonheartbeating donors is unclear. Research has shown that livers of female rats develop a greater degree of intracellular acidosis during ischemia than males. This work explores the role of sex hormones in mediating this sex difference.


METHODS
Subgroups of neutered female rats were given 17 beta-estradiol (E), progesterone (P), or combination (E+P). To compare the effects of female sex hormones in males, subgroups of intact and castrated males received 17 beta-estradiol. In vivo and ischemic liver biopsies were taken and analyzed for lactate and H.


RESULTS
Although there was no effect of hormone therapy on baseline metabolic parameters, during ischemia compared to neutered females, livers from E females significantly (P<0.01) increased lactate by 56% and H+ by 71%, while E+P significantly increased only lactate (39%; P<0.05). Livers from neutered males given 17 beta-estradiol showed significantly greater (P<0.001) accumulation of lactate (80%) and H+ (79%). This was even shown in intact males, where despite a blunted response, 17 beta-estradiol, significantly (P<0.05) increased lactate by 39% and H+ by 25%.


CONCLUSIONS
This study illustrates the mechanisms for the sex difference in the liver's metabolic response to ischemia are estrogen mediated, which is seen even in the presence of male hormones, thus offering one explanation for the lower liver transplant success when the donor is female.
Soric
Stjepan
S
Department of Physiology, Medical Sciences Building, University of Toronto, Toronto, Canada.
Belanger
Michael P
MP
Askin
Nesime
N
Wittnich
Carin
C
D000140:Acidosis, Lactic / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism; D019344:Lactic Acid / Q000032:analysis; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D012737:Sex Factors
D012739:Gonadal Steroid Hormones; D019344:Lactic Acid; D011374:Progesterone; D004958:Estradiol; D006859:Hydrogen