The mechanisms of the responses of an enzyme to different hormones and 
metabolites or several enzymes to a single hormone are surprisingly varied. 
There is neither an operon for lipogenic enzymes nor a common step at which 
hormones and metabolites coordinately regulate the expression of lipogenic 
genes. In bacteria, coordinated expression of several enzymes in a single 
metabolic pathway often is achieved by organizing the genes into operons. An 
operon is a group of genes linked together in a linear fashion and producing a 
polycistronic mRNA. Trans-acting factors regulate the transcription of these 
genes by interacting with promoter/regulatory sequences in the 5'-flanking 
region of the most 5'-ward of the genes. In vertebrate animals, however, 
coordinated control of gene transcription is not achieved by linking the 
individual genes, but by putting in the 5'-flanking regions of these genes a 
regulatory sequence that interacts with common trans-acting factors. Genes 
controlled by different hormones are expected to have regulatory elements for 
each hormone. The presence of glucocorticoid and cyclic AMP regulatory elements 
at the 5'-end of the PEPCK gene is consistent with this notion. Transcription is 
not the only step at which hormones and metabolites control the pathways for 
gene expression. The levels of the mRNAs for L-PK, ME, S11, and S14 are 
increased by T3 at post-transcriptional steps. Glucagon also regulates the 
accumulation of ME mRNA post-transcriptionally. Neither the mechanism nor the 
sequence organization of regulatory elements is known for post-transcriptional 
control of gene expression. In the case of PEPCK and HMG-CoA reductase, the next 
steps will be to determine more precisely the sequences in the 5'-region that 
mediate hormone sensitivity and feedback inhibition, respectively, and whether 
trans-acting factors are involved. For the other genes discussed, identification 
of the regulated step must precede identification of sequences that confer 
hormone or metabolite-sensitive regulation on a specific gene. In general, it is 
probable that the hybrid gene approach, so successful for PEPCK and HMG-CoA 
reductase, also will be effective in defining cis-acting hormone- or 
metabolite-regulatory elements in other genes. These techniques should be 
applicable to both transcriptional and post-transcriptional mechanisms. Our 
long-term objective is to understand the molecular basis of each event that 
intervenes between the binding of hormone or metabolite to its appropriate 
receptor and altered enzyme level.(ABSTRACT TRUNCATED AT 400 WORDS)