Hormonal control of "tissue" transglutaminase induction during programmed cell death in frog liver

In this study, we show that sex hormones (testosterone, estradiol, and prog esterone) act as physiological modulators of programmed cell death (PCD) du ring the frog liver involution observed postvitellogenesis. PCD in parenchy mal cells is paralleled by the specific induction of the "tissue" transglut aminase (tTG) gene. tTG protein specifically accumulates in hepatocytes sho wing the morphological features of apoptosis. The hormone-dependent increas e of both PCD and tTG was reproduced in ovariectomized frogs. Treatment of castrated animals with testosterone, estradiol, and progesterone inhibited the induction of both tTG; and PCD, thus indicating that in vivo the drop i n the circulating sex hormone is the signal favoring the involution phase o f the maternal frog liver after mating. Although an affinity-purified polyc lonal antibody raised against mammalian transglutaminase reacts in frog liv er with a 55- to 60-kDa protein, concomitant with the onset of PCD, tTG; cl eavage products were detected, suggesting a proteolytic processing of the e nzyme protein. These results represent the first evidence indicating that t he physiological involution occurring postvitellogenesis of frog liver take s place by programmed cell death and that this, together with the concomita nt induction of tTG gene expression, is regulated by sex hormones. (C) 1999 Academic Press.