STEROID SEX HORMONES 



(359 



of action of estrogens at the biochemical 

 level remains to be elucidated, but the 

 data available permit the formulation of a 

 detailed working hypothesis. The notable 

 effects of estrogens and androgens on be- 

 havior (see chapter by Young) are pre- 

 sumably due to some direct or indirect ef- 

 fect of the hormone on the central nervous 

 system. The explanation of these phenomena 

 in physiologic and biochemical terms re- 

 mains for future investigations to provide. 



B. ANDROGENS 



Although there is a considerable body of 

 literature regarding the responses at the bio- 

 logic level to administered androgens and 

 progesterone, much less is known about the 

 site and mechanism of action of these hor- 

 mones than is known about the estrogens. 

 The review by Roberts and Szego (1953b) 

 deals especially with the synergistic and 

 antagonistic interactions of the several 

 steroidal sex hormones. 



The rapid growth of the capon comb fol- 

 lowing the administration of testosterone 

 has been shown to involve a pronounced 

 increase in the amount of mucopolysac- 

 charide present, as measured by the content 

 of glucosamine (Ludwig and Boas, 1950; 

 Schiller, Benditt and Dorfman, 1952). It 

 is not known whether the androgen acts by 

 increasing the amount or activity of one of 

 the enzymes involved in the synthesis of 

 polysaccharides or whether it increases the 

 amount or availability of some requisite 

 cofactor. Many of the other biologic effects 

 of androgens do not seem to involve 

 mucopolysaccharide synthesis and the 

 relation of these observations to the 

 other roles of androgens remains to he de- 

 termined. 



Mann and Parsons (1947) found that 

 castration of rabbits resulted in a decreased 

 concentration of fructose in the semen. 

 Within 2 to 3 weeks after castration the 

 amount of fructose in the semen dropped 

 to zero, but rapidly returned to normal fol- 

 lowing the subcutaneous implantation of a 

 pellet of testosterone. Fructose reappeared 

 in the semen of the castrate rat 10 hours 

 after the injection of 10 mg. of testosterone 

 (Rudolph and Samuels, 1949). The coagu- 

 lating gland of the rat, even when trans- 



planted to a new site in the body, also re- 

 sponds by producing fructose when the host 

 is injected with testosterone. The amount 

 of citric acid and ergothioneine in the semen 

 is also decreased by castration and in- 

 creased by the implantation of testosterone 

 pellets (Mann, 1955). The experiments of 

 Hers (1956) demonstrate that fructose 

 is produced in the seminal vesicle by 

 the reduction of glucose to sorbitol and 

 the subsequent oxidation of sorbitol to 

 fructose. The reduction of glucose re- 

 quires TPNH as hydrogen donor and the 

 oxidation of sorbitol requires DPN as 

 hydrogen acceptor. The sum of these two 

 reactions provides for the transfer of hy- 

 drogens from TPNH to DPN. If androgens 

 act as cofactors which are reversibly oxi- 

 dized and reduced, and thus transfer hy- 

 drogens from TPNH to DPN as postulated 

 by Talalay and Williams-Ashman (1958), 

 one would expect that an increased amount 

 of androgen, by providing a competing sys- 

 tem for hydrogen transfer, would decrease 

 rather than increase the production of fruc- 

 tose. The marked increases in the citric 

 acid and ergothioneine content of semen 

 are not readily explained by this postulated 

 site of action of androgens. 



An increase in the activity of /3-glu- 

 curonidase in the kidney has been reported 

 following the administration of androgens 

 (Fishman, 1951). This might be interpreted 

 as an arlaptive increase in enzyme induced 

 by the increased concentration of substrate, 

 or by a direct effect of the steroid on the 

 synthesis of the enzyme. 



The respiration of slices of prostate gland 

 of the dog is decreased by castration or by 

 the administration of stilbestrol (Barron 

 and Huggins, 1944). The decrease in respi- 

 ration occurs with either glucose or pyruvate 

 as substrate. The seminal vesicle of the rat 

 responds similarly to castration. Rudolph 

 and Samuels (1949) found that respiration 

 of slices of seminal vesicle is decreased by 

 castration and restored to normal values 

 within 10 hours after the injection of tes- 

 tosterone. Experiments by Dr. Phillip Corf- 

 man in our laboratory with slices of prostate 

 gland from patients with benign prostatic 

 hypertrophy showed that oxygen utilization 

 was reduced 50 per cent by estradiol added 



