P. N. Campbell

Hormonal regulation of specific gene expression

A FEBS Advanced Course (No. 53) was held September 1%22,19?8 at The Mjd~e~x Hospital Medical School an the ?-Iormonal Reg~a~o~ of Specific Gene Expression’. The course coincided wi& the celebrations to mark the 50th Anniversary of the Foundation of the Courtauld Institute of Biochemistry. A Symposium was held on the first day at which the speakers surveyed various aspects of the subject for the comparative nonexpert. The subsequent course lasted two and a half days and consisted of talks by invited speakers and shorter contributions from participants. As with the last caurse on a related but different subject [FEBS Letters (1976) 72,215-2261 we, as organizers, were asked to produce a survey of the papers presented and of the discussion and in particular to provide a bibliography that would serve as an entree to the field. Rather than try to provide a blow by blow account we have tried to pinpoint the present status of the various aspects af the subject. All the major contributors have had an opportunity to comment on a draft report and we hope that there is a reasonabie concensus concerning the views expressed. The plan of the course was to consider first the progress that has been made in developing cell cultures that have either been shown to respond to hormones or have the potential of doing so. There followed several sessions in which current work on various hormones was considered in turn. Particular emphasis was placed on the use of in vitro systems, either cell cultures or explants. In the last session the contribution of current developments in recombinant DNA research to endocrinology was reviewed. There are two broad approaches to an understanding of gene expression in eukaryotes. Either one can utilize systems in which a few well-defined prateins are produced in response to specific stimuli, or one can study systems in which the specific genes of interest are reiterated to such a degree that they may be isolated by physical means alone. The present course was almost entirely confined to examples of the first of the two approaches.

SYNTHESIS AND PROCESSING OF MILK PROTEINS

Publisher Summary This chapter reviews synthesis and processing of milk proteins. Until recently, the major interest in milk proteins was derived from the observation that the limited number of major protein constituents present were organ specific and that their expression was modulated by a well-defined combination of both peptide and steroid hormones. Experiments concerning the intracelluiar mechanisms involved in the synthesis and processing of secretory proteins are based fundamentally on the pioneering work of Siekevitz & Palade who proposed that membrane-bound polyribosomes represented the site of synthesis of secretory proteins, whereas proteins required for intracelluiar functions were synthesized on free polyribosomes. The major secretory component of the liver serum albumin is synthesized primarily on membrane-bound polyribosomes, whereas ferritin, the major intracellular iron-storage protein, is synthesized primarily on free polyribosomes. Evidence for the presence of precursors for guinea-pig caseins is indirect, and it has been derived from comparative analysis of mRNA-directed milk-protein synthesis in protein synthesizing systems containing either intact endoplasmic reticulum or fragments thereof.

Biosynthesis of proteins.

I here can be little doubt that the specific information necessary for the biosynthesis of proteins is, in some way, woven into the structure of the deoxyribonucleic acids of the chromosome. Ample support for this conclusion is given by the numerous observations that have related Mendelian genes to individual protein molecules. As we have seen, the most direct evidence has come from instances in which the genetic results could be compared with the chemical and physical properties of isolated, homogeneous proteins, such as hemoglobin, tyrosinase, and p-lactoglobulin. Equally convincing are the results obtained by bacteriologists and virologists who have demonstrated that highly purified samples of DNA are capable of modifying both the genotype and phenotype of recipient cells, or of inducing the formation of the relatively complicated protein complex which characterizes the bacteriophage particle. It is clear, however, that protein synthesis can take place outside the nucleus itself. In the reticulocyte, for example, hemoglobin synthesis proceeds at a rapid rate, and not until the cell has become a mature erythrocyte does such synthesis cease. Similarly, in the alga Acetabuluria mediterranea, whose cell may be separated into nuclear