Tissue specificity of steroid hormone action: A new theory

Abstract

A major problem still to be solved in endocrinology is that of tissue specificity of steroid (and other) hormone action. For example, ecdysone is known to co-induce the synthesis of different proteins in fat body, epidermis, salivary glands, etc. In flies the vitellogenin genes are only expressed in the fat body of adult females in response to 20-OH-ecdysone. This is a result of differentiation having occurred during development. The nature of differentiation is the generation of asymmetry. In somatic cells of developing animals and plants the asymmetry does not seem to reside in the DNA itself [e.g. experiments of Gurdon (1962) Devl Biol. 4, 256–273 and (1974) The Control of Gene Expression in Animal Development, p. 160. Clarendon Press, Oxford] but rather in the mechanisms which make use of genetic information. Control of gene expression is very complex: in addition to mechanisms operating at the level of DNA/RNA, there are also epigenetic phenomena, some of which are localized in the plasma-membrane. Asymmetry can only be introduced in a reproducible way by those molecular mechanisms which have a well defined and constant location in the cell and which are not subject to diffusion. A typical feature of differentiating cells is that they divide asymmetrically. Considering data which have recently become available, the plasma-membrane presents itself as a good candidate for the location of molecules contributing to this asymmetric development. In order to be of any importance for steroid hormone action the properties of the plasma-membrane (especially permeability) should differ between different cell types, should be influencible by steroids, and there should be a causal relationship between membrane permeability and nuclear activity. Besides receptors within the cell, some steroid hormones also seem to have plasma-membrane receptors. Tissue specificity of steroid hormone action may be determined largely by the properties of the cell membranes (plasma- and also, perhaps, nuclear membranes). Steroids may act at different levels within the cell.