Activation and Regulation of the Vitellogenin Gene Family

Abstract

Steroid hormone-regulated systems have played an important role in furthering our understanding of how the interaction between the hormonereceptor complex and the genome might initiate or modulate the physiological changes in the hormone’s target cells. With the advent of recombinant DNA technology, major emphasis has been placed on DNA sequences that are important for regulation by the hormone-receptor complex, best illustrated by the recent work on regulation by estrogen, androgen, and glucocorticoids of genes encoding egg proteins, mammary tumor virus, and α_2u-globulin (for several recent reviews see Eriksson and Gustafsson, 1983; Chambon et al., 1984; Renkawitz et al., 1984; Payvar et al., 1983). Attention is now being focused on the implications of the structure of the nucleus in modulating specific gene activity, such as the association of steroid harmone receptors and harmone-regulated genes with the target cell’s nuclear matrix or scaffold (Barrack and Coffey, 1983; O’Malley et al., 1985). This Chapter is largely based on recent work from the author’ laboratory on the regulation of Xenopus vitellogenin genes by estrogen. Much of the work involves the manipulation of this gene family in primary cell cultures in which the full physiological process can be reversibly reproduced. It also describes how heat shock and cellular stress produced in setting up cultures can modify the action of estrogen. Finally, some recent results obtained in our laboratory on specific switching on in vitro of the silent vitellogenin genes in nuclei isolated from male Xenopus hepatocytes by soluble extracts are also described. In addition, it is intended to point out those areas of possible fruitful investigation in the future that are likely to further our outstanding of the different elements that determine hormonal regulation of gene expression.