92 Essays in Biochemistry 



and might be considered to serve at least some of its functions at such 

 an interface — a cell membrane, for example. In order to explain the 

 high activity of these compounds on a weight basis it must further 

 be assumed that there are highly specific binding sites for steroid 

 hormones. At a cell membrane, a steroid hormone could conceivably 

 exercise control over intracellular biochemical reactions by hindering 

 or facilitating the passage of key metabolites through the cell mem- 

 brane in either direction. It is equally possible that similar control 

 could be cxerciM'd within the cell at some phase boundary. 



Is there any evidence for such a view? There are certain indirect 

 suggestions which may be pertinent. One of the most interesting- 

 characteristics of the steroid compounds generally is their propensity 

 for complexing. The classical example, of course, is digitonide forma- 

 tion which has now become so commonplace a tool to the steroid 

 chemist that its physical significance has perhaps been overlooked. 

 The ability to form stable, insoluble complexes with digit onin is shared 

 by essentially all steroids possessing ^-oriented hydroxy! groups at 

 carbon 3 but is not necessarily limited to such compounds. This is a 

 typical example of a steroid-steroid interaction, of which many exist. 

 If one now considers the interaction of 3/3-hydroxy steroids with satu- 

 rated A and B rings, one can subdivide the interaction into what might 

 be considered as first- and second-order effects. The examination of 

 the solubility products of representative digitonides reveals that, in 

 general, those compounds having the 3/3,5/3 (axial I conformation have 

 higher solubility products than those possessing the 3/?,5a (equatorial) 

 conformation. This would seem to suggest that both the hydroxyl 

 groups and the nature of the ring fusions or a combination of these 

 two factors are concerned in the digitonide formation. 



A second type of interaction is that shown by deoxycholic acid and 

 apocholic acid, which form very tight inclusion or clathrate complexes 

 with a wide variety of substances. Although it may be argued that 

 these very stable complexes cannot play any significant biological role 

 because of the extremely low concentration of free bile acids in body 

 fluids, the possibility remains that the bile salts participate in a similar, 

 but looser, form of complexing in the intestinal tract. In any case 

 their surface activity would make them highly oriented at phase 

 boundaries. 



A third, biologically important, type of complex involving steroids 

 is the binding to plasma proteins. These complexes, some of which 

 have been subjected to detailed physicochemical study, are undoubt- 



