Expression of apoptosis-related genes in liver-specific growth hormone receptor gene-disrupted mice is sex dependent.

ABSTRACT

Apoptosis is a process that affects life span and health. Mice with liver-specific disruption of the growth hormone receptor (GHR) gene (ie, Ghr gene) liver-specific growth hormone receptor knockout [LiGHRKO] mice), as opposed to mice with global deletion of the Ghr gene (GHRKO; Ghr-/-), are characterized by severe hepatic steatosis and lack of improved insulin sensitivity. We have previously shown that levels of proapoptotic factors are decreased in long-lived and insulin-sensitive GHRKO mice. In the current study, expression of specific apoptosis-related genes was assessed in brains, kidneys, and livers of male and female LiGHRKO and wild-type mice using real-time PCR. In the brain, expression of Caspase 3, Caspase 9, Smac/DIABLO, and p53 was decreased in females compared with males. Renal expression of Caspase 3 and Noxa also decreased in female mice. In the liver, no differences were seen between males and females. Also, no significant genotype effects were detected in the examined organs. Lack of significant genotype effect in kidneys contrasts with previous observations in GHRKO mice. Apparently, global GHR deletion induces beneficial changes in apoptotic factors, whereas liver-specific GHR disruption does not. Furthermore, sexual dimorphism may play an important role in regulating apoptosis during liver-specific suppression of the somatotrophic signaling.