Human 6-phosphofructokinase (EC 2.7.1.11) exists in tetrameric isoenzymic forms composed of muscle (M), liver (L) and platelet (P) subunits, which are under separate genetic control. In the adult, the proportion of these subunits in different organs reflects the relative activity of glycolysis versus gluconeogenesis. To elucidate the developmental basis for the observed distribution, we investigated the isoenzymic transitions of phosphofructokinase in human foetuses (12-40 weeks' gestation) by using high-resolution chromatography and monoclonal antibodies. We studied skeletal muscle, heart, liver and brain because these organs show very different glycolytic fluxes and isoenzymic patterns in adult individuals. Our results demonstrate that there is no unique 'foetal' form of phosphofructokinase in humans, but all three loci are variably expressed in all foetal organs during early gestation. As development proceeds, muscle and liver isoenzyme patterns show dramatic changes, with disappearance of P and L subunits in muscle and transient reappearance of M and P subunits in liver; in contrast, phosphofructokinase isoenzymes change little in brain and heart. Most changes occur at mid-gestation and near term, and adult isoenzyme patterns are expressed at birth, indicating that organ differentiation is complete. These studies show that phosphofructokinase undergoes changes of isoenzyme patterns similar to, but not identical with, those of other multilocus isoenzyme systems of glycolysis. The observed changes probably reflect changing patterns of gene expression, with repression of some loci and activation of others.

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tional interest was the analysis of sex chromatin distribution and estrogen receptor protein (ERP) in breast carcinomas. Sex chromatin counts were obtained from imprints made directly from the same tumor samples submitted for ERP analysis at the time of biopsy. Substantially lower sex chromatin counts were found in ERP-negative primary tumors than in ERP-positive carcinomas. These results may explain the more favorable prognosis associated with Barr chromatin body-positive breast carcinomas.2 Also, on the basis of this observation, we have specu¬ lated that a gene locus associated with the production or action of ERP is X-linked. Since there appeared to be no consistent relationship between ERP and sex chromatin count in métastases, we considered it possible that interval therapy might have altered the cells and obscured Barr chromatin bodies.