The cluantitative pattern of enzymes in the seconcl trimester h u~n a n fetal liver is sigllificantly different fro111 that of aclult liver.For some 20 enzymes, the activity quotient (AQ, i.e., activity of i n~n~a t u r e liver divicled by that in atlult liver) is appreciably different front 1.0. RIost of the enzynles increase their concentrations with age but, as one would expect, sollie contribute to differentiation by tlin~inishing in amount.In cleveloping hurnan liver the concentrations of the various enzynles tend to change in the sanle clirection as they d o in rat liver. 'I'hose that incriase in rat liver have been classifietl into three tnain cIu~ters, accortling to whether their rise begins o n about the 17th day of gestation (B), the first neonatal day (C), or just before weaning (D), respectively. The distribution of these enzynles anlong these three clusters correlates with their AQ's in the hutnan fetal liver. 111 general, enzyrnes with A Q around 0.5 belong to cluster (B) in rat liver whereas those with 0-0.16 belong to cluster C or D.Gross n~alforn~ations resulting fro111 the teratogenic action of drugs, hormones, or vitaniins on the early enlbryo attract n~ucll attention. The harn~ful in~pacts of such agents at late stages of gestation are less spectacular. 'They rnay be more frequent, however, ant1 inanifest then~selvcs in perlnanent inatlecluacies in n~etabolisn~ or growth with a tendency to succun~b to minor childhood cliseases. The underlying causes nlay not be n~irrored in the cytocolnposition or even the subcellular nlorphology -of autopsy specimens. Only deviations from the organ characteristic quantitative pattern of gene products woulcl provide sensitive enough inclictors of the metabolic lesions and of the aberrant aspects of differentiatiol~ that were responsible for them. In both the presence ancl absence of detectable ~norphologic abnornlalities, the stutly of enzymes, this rnost varied and largest class of specific chen~ical constituents, would greatly extend the resolving power of the usual diagnostic procedures postmortem.
SpeculationThe sequence in which clifferent enzymes approach their adult concentration in human liver closely resembles that in rat liver.'I'his s~~g g e s t s that the n~echanislns responsible for the scheclule of gene expression rnust also be analogous: the synthesis of specific groups of enzynles at each correspondir~g critical period is regulated by the sarne horniones in both species. Hence, the "cnzyn~e pathology" of infant livers not only specifies basic n~etabolic lesions: aidecl by observations on the rat ~noclel, it coultl also identify the age of onset and the kind of aberrations in the fetal environment which initiated the lesions.