Orthotopic liver transplantation and the cytosolic estrogen-androgen receptor status of the liver: The influence of the sex of the donor

Abstract

Mammalian liver is known to contain cytosolic receptors for both estrogens and androgens. Furthermore, certain mammalian hepatic functions are known to display a sexual dimorphism. However, in clinical liver transplantation, the sex of the donor is not taken into consideration in selection of the donor. In this study, the effect of liver transplantation on the estrogen and androgen receptor content of the liver was determined. Adult male and female rats were subjected to orthotopic liver transplantation, using donors from both the same and the opposite sex as the recipient. The animals were killed on the tenth postoperative day, and the livers were assayed to determine their cytosolic estrogen and androgen receptor content. Transplantation of a liver from a male donor into a male recipient, from a male donor into female recipient and from a female donor into a male recipient produced similar changes in the number of cytosolic estrogen and androgen receptors in hepatic cytosol. In all three situations, the estrogen receptor content in the cytosol of the transplanted liver was the same as that found in an unoperated male liver, and the cytosolic content of the androgen receptor was the same as that of an unoperated female liver. After transplantation of the liver from a female donor into a female recipient, the estrogen and androgen receptor content in the cytosol of the transplanted liver was the same as that of an unoperated female.(ABSTRACT TRUNCATED AT 250 WORDS)

Higher Risk of Posttransplant Liver Graft Failure in Male Recipients of Female Donor Grafts Might Not Be Due to Anastomotic Size Disparity

“…31 A previous study in rats demonstrated that female-to-male liver transplantation significantly reduced the cytosolic estrogen receptors in grafts to the level of male liver within 10 days, whereas male-to-male liver transplantation maintain the estrogen receptor content. 9 Abrupt defeminization of female livers by reduction of estrogen receptor activity and exposure to the male hormonal milieu can impair mechanisms of protection of grafts from female donors.…”

Maternal grafts protect daughter recipients from acute cellular rejection after pediatric living donor liver transplantation for biliary atresia

“…Some reports have indicated that gender mismatch has an impact on graft failure, specifically in male recipients receiving grafts from female donors in adult deceased donor LT and adult LDLT . Although the poor graft prognosis was thought to result from reduced serum estrogen levels in male recipients and a lower number of estrogen receptors in male recipients of grafts from female donors , further long‐term study is warranted to clarify how hormonal factors affect the outcome of LT. In contrast, Nijagal et al .…”

Donor gender does not affect liver transplantation outcome in children

“…Certainly, one of the responses of the liver to exogenously administered estrogen is to enhance its synthesis of various transport proteins including sex-steroid-binding globulin (2) and thyroxine-binding globulin (12). In addition, the presence of specific estrogen-binding proteins within the liver, which presumably protect male hepatocytes from the unwanted effects of estrogen, have been identified and characterized in the liver (4). The amount of these proteins in the hepatic cytosol after puberty differ markedly between males and females (6).…”

“…In animal studies, transplantation of organs from adult donors of one sex (male or female) to a recipient of the opposite sex results in the finding of cytosolic estrogen and androgen receptor activity similar to those found in female liver (4). These changes in the sex hormone-receptor expression of the liver have been postulated to account for the unfavorable outcome associated with transplantation of organs harvested from females that are subsequently transplanted into adult males (5).…”

“…With the increasing success and number of liver transplant procedures and centers throughout the world, the emphasis at these centers has been directed towards identifying factors that determine outcome. For several years now the liver has been recognized as a sex hormone-responsive organ (1)(2)(3)(4). The observation that the levels of sex hormone receptors within the liver differ between the sexes after puberty has raised questions relative to donor liver function, phenotypic expression, and overall outcome (survival and/or graft failure) when an organ obtained from an individual of one gender is transplanted into an individual of a different gender (5).…”