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Reversal of phenobarbital‐induced hyperplasia and hypertrophy in the livers of lpr mice
Author(s) -
SARRAF C.E.,
HORGAN M.,
EDWARDS R.J.,
ALISON M.R.
Publication year - 1997
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1046/j.1365-2613.1997.d01-238.x
Subject(s) - apoptosis , endocrinology , medicine , hyperplasia , hepatocyte , muscle hypertrophy , phenobarbital , fas receptor , atrophy , biology , chemistry , programmed cell death , in vitro , biochemistry
Fas is a cell surface receptor that mediates apoptosis, and Fas mRNA has been demonstrated in hepatocytes. MRL/MP ‐ lpr/lpr mice carry the mutated lymphoproliferation‐associated gene, lpr , that codes for truncated Fas protein, resulting in reduced apoptotic potential in some circumstances. Phenobarbital treatment of experimental animals induces cytochrome P450 enzymes, and thus acts as a growth stimulus to the liver with both hyperplasia and hypertrophy; cessation results in reversion of liver to normal size with apoptosis playing a role. This study has determined the respective contributions of atrophy and apoptosis to this involution in Fas‐defective and normal‐Fas bearing animals. Between the first day and the fifth day after phenobarbital cessation, the weights of both Fas‐defective ( lpr/lpr ) livers and control ( lpr /+) livers reduced. Hepatocyte hypertrophy gradually reverted in both categories of mouse and this was the greater contribution to reduction in liver size. In lpr/lpr animals, there was a consistent level of apoptosis which remained relatively constant, while numbers of apoptotic cells in control livers increased over the period. This investigation has shown that in liver, a mechanism to execute apoptosis is operative even in Fas‐defective mice, but it is not sensitive to signals activated by the removal of the growth stimulus. This is in contrast to mice which can mount a Fas‐mediated response; thus a separate apoptotic pathway is indicated.