This group of steroids has two polar groups, one at C3 and one at C17. The energetic center at C3 can have negative or positive polar characters, according to the presence of oxygen or hydroxyl. The energetic center at C17 also can have an oxygen or hydroxyl group and thus be negative or positive. An important factor for the properties of the substance is the relationship between the two polar groups in the same molecule. It is apparent that the polarity of the molecule will vary according to what polar groups are present at C3 and C17. In a very simplified concept, which we consider only partially accurate, we have tried to associate female and male hormonal characteristics with this polarity.

In the simple steroid molecules, a folliculinoid or estrogenic biological property seems to be conferred if the two polar groups—at C3 and C17 —are formed by hydroxyls. The molecule appears to have a dipositive polarity. It seems to be important that the two hydroxyls be kept in the relatively fixed reciprocal positions—corresponding to C3 and C17—as part of the solid skeleton of the steroids. Estrogenic properties are present in various steroids that fulfill this condition. Furthermore, substances far removed from the steroids have folliculinoid properties if they have this relationship between the two hydroxyls. As shown in Figure 66 diethyl stilbestrol, which has its two hydroxyls maintained in a fixed relative position similar to that of steroid estrogens, also shows potent estrogenic activity.

Estradiol

Estradiol

Diethylstilbestrol

Diethylstilbestrol

Fig. 66. The folliculinoid activity appears to be related to the existence of two hydroxyls kept at the same relative position, as it appears in estradiol and in diethylstilbestrol.

In the same way, we tried to correlate testoid activity with the presence of positive negative polarity; that is, with two polar centers energetically different, one corresponding to an oxygen and the other to a hydroxyl, maintained in the same fixed relative position. The importance of this relative steric position of the two polar groups for testoid activity becomes evident when it is found in substances other than testosterone, the principal male hormone, with an oxygen at C3 and a hydroxyl at C17. Testoid activity is present in androsterone, which has an oxygen and an hydroxyl maintained in the same reciprocal positions, although here the oxygen is at C17 and the hydroxyl at C3, the reverse of testosterone. In both substances, testosterone and androsterone, the two conditions for testoid activity, positive negative polarity and the same relative position between the polar groups, are fulfilled. (Fig. 67) The differences which exist between these substances in their specific hormonal activity can be explained through the different influence exerted upon the two polar groups in these substances by the rest of the molecules.

Testosterone

Testosterone

Androsterone

Androsterone

Fig. 67. The testoid activity seems to be related to the presence of a hydroxyl and a carbonyl in the same fixed relative position which is insured by the rigidity of the steroid molecule. The same positional reciprocal relationship is seen to exist between these two polar groups in testosterone and androsterone.

The testoid activity seen for cortisone, hydrocortisone and other hormones also can be explained by the presence in these molecules of oxygen and hydroxyl at C3 and C17, and maintenance of the fixed position between these two polar groups.

Conceptually, the antagonism between estrogenic and testoid biological activities can be considered to be ultimately related to the differences in polarity, which in one form or another can be found in other factors differing for the sexes. We will mention here only that a similar difference between male and female character is seen in the sexual chromosomes, where the female character is related to the XX chromosome, and the male to an X and a Y chromosome. As we will see below, a relationship exists between lipids in general and sex.

Besides the sex hormones, fatty acids appear to be connected with male sex characteristics, while female characteristics are related to another group of steroids, the sterols.