90 Essays in Biochemistry 



estradiol-17a. It is difficult to set up the requirements for estrogenic 

 activity of organic compounds, since a variety of natural and synthetic 

 substances, some of which are unrelated to the steroid compounds, 

 possess this type of activity. 



More rigid restrictions upon structure are present in the androgen 

 series. The minimum seems to be oxygen functions at carbons 3 and 

 17 and trans fusion of rings A and B. Obliteration of the asymmetry 

 at carbon 5 by unsaturation does not interfere with biological activity. 

 As in the case of the estrogens, those 17/3-hydroxy compounds which 

 are biologically active are considerably more potent androgens than 

 the corresponding 17a-hydroxy compounds. 



Progesterone has the highest activity of any thus far recognized 

 naturally occurring progestational compound. It possesses the unsatu- 

 rated ketonic linkage in ring A characteristic of most of the naturally 

 occurring neutral steroid hormones, and in addition, a carbonyl group 

 at carbon 20. It should be noted here that, as in the case of cholesterol, 

 the 2-carbon side chain in progesterone possesses the (3 configuration 

 and that epimerization results in loss of biological activity. Alteration 

 of any of the functional groups on the progesterone molecule results 

 in complete abolition of biological activity. However, a number of 

 compounds closely related to progesterone have been prepared which 

 show activity equal to or even greater than that of the natural hormone. 



In the cortical steroid series several qualitatively different types of 

 biological activity are present; among them are the regulation of elec- 

 trolyte metabolism and of carbohydrate metabolism. Aldosterone is 

 the most potent steroid known insofar as electrolyte regulation is con- 

 cerned, whereas hydrocortisone exerts its principal effect upon carbo- 

 hydrate metabolism. However, both of these steroids possess to a 

 limited extent the activity characteristic of the other. In addition, 

 steroids intermediate in both biological activity and in chemical struc- 

 ture have been isolated from adrenal cortical extract and constitute 

 a series in which activity shifts stepwise from predominantly electro- 

 lyte to predominantly carbohydrate regulatory as hydroxyl and car- 

 bonyl groups are added or removed from specific carbon atoms in the 

 molecule. 



This very cursory survey of the relation between structure and bio- 

 logical activity has served primarily to emphasize the point that the 

 biological activity of the steroid hormones seems to be less dependent 

 upon the nature of the functional groups than upon their relative 

 positions on the nucleus and their configurations. Apparently no new 

 kinds of chemical reactivity have been conferred upon the molecules 



