Steroid Hormones 89 



it would seem that the adrenal cortex is nut required for life when 

 environmental conditions arc held constant. However, alterations in 

 environmental conditions may precipitate changes which can be re- 

 versed only by the institution of specific hormonal replacement t herapy. 

 If one makes the reasonable assumption that, in the experimental ani- 

 mals cited above, functioning residual gonadal or adrenal tissue is not 

 present, then it would seem safe to conclude that the steroid hormones 

 are not required for the basic, obligatory, biochemical reactions which 

 proceed in the cell. This conclusion would also seem to follow from 

 considerations of the appearance of hormones in the evolutionary se- 

 quence above the level of unicellular organisms. It would appear, 

 then, that hormones may be considered as agents elaborated by one 

 cell type which influence the physiologic behavior of other cells. This 

 concept is, in tact, implicit in the definition of a hormone. Thus the 

 hormones may be in a somewhat different category from the vitamins, 

 at least those of the B complex, many of which serve as coenzymes in 

 obligatory metabolic reactions. 



In order to examine this question more closely it seems desirable 

 to digress briefly and discuss some general features of steroid structure. 

 The common feature possessed by all these compounds is the tetra- 

 cyclic nucleus with its complement of one or two angular methyl groups. 

 Side chains of varying length may be attached to carbon 17. Exami- 

 nation of a close-packed model of this nucleus reveals many features 

 not apparent from consideration of the conventional two-dimensional 

 representation. The nucleus occupies space in a characteristic fashion, 

 and the substituents on the nucleus are rather more restricted in their 

 relative positions than is apparent in the planar formulas. When 

 oxygen functions, such as hydroxyl or carbonyl groups, are attached 

 to the nucleus, they confer upon the compounds additional asymmetry 

 which gives to each molecule characteristic aspects of front, back, top, 

 bottom, and two sides. All of the naturally occurring steroid hormones 

 thus far recognized bear an oxygen-containing substituent at carbon 3, 

 as well as other oxygen functions. In addition, unsaturated linkages 

 may be present. The nature and locations and the configurations of 

 the substituents determine both the character and the intensity of the 

 biological activity. 



Structural specificity is relatively low in the estrogen series, all three 

 of the principal human estrogens, estrone, estradiol, and estriol possess- 

 ing a considerable degree of activity. Nevertheless, a change in the 

 configuration of the 17-hydroxyl group converts estradiol-17/?, the most 

 potent known natural estrogen, to a relatively inactive compound, 



