660 



PHYSIOLOGY OF GONADS 



in vitro at a level of 1 /xg. per ml. Respira- 

 tion of slices of the ventral prostate gland 

 of the rat is decreased by castration and in- 

 creased by administered testosterone (Ny- 

 den and Williams-Ashman, 1953). These 

 workers showed that lipogenesis from ace- 

 tate-l-C^* in the prostate is also sig- 

 nificantly diminished by castration and 

 restored to normal by administered testos- 

 terone. 



The succinic dehydrogenase of the liver 

 has been found to be increased by castration 

 and decreased by the administration of tes- 

 tosterone (Kalman, 1952; Rindani, 1958), 

 the enzyme is also inhibited by testosterone 

 added in vitro (Kalman, 1952). In contrast, 

 Davis, Meyer and McShan (1949) found 

 that the succinic dehydrogenase of the 

 prostate and seminal vesicles is decreased 

 by castration and increased by the admin- 

 istration of testosterone. 



An interesting example of an androgen 

 effect on a specific target organ is the de- 

 creased size of the levator ani and 

 other perineal muscles of the rat fol- 

 lowing castration. The administration of 

 androgen stimulates the growth of these 

 muscles and increases their glycogen content 

 (Leonard, 1952). However, their succin- 

 oxidase activity is unaffected by castration 

 or by the administration of testosterone. 

 Courrier and Marois (1952) reported that 

 the growth of these muscles stimulated by 

 androgen is inhibited by cortisone. The 

 remarkable responsiveness of these muscles 

 to androgens in vivo gave promise that 

 slices or homogenates of this tissue incu- 

 bated with androgens might yield clues as to 

 the mode of action of the male sex hor- 

 mones. Homogenates of perineal and mas- 

 seter muscles of the rat responded to andro- 

 gens administered in vivo with increased 

 oxygen consumption and ATP production 

 iLoring, Spencer and Villee, 1961). The ex- 

 periments suggested that the activity of 

 DPNH-cytochromo r reductase in these 

 tissues is controlled by aiKh'ogeiis. 



C. PROGESTERONE 



Attempts to clarify the biochemical basis 

 of the role of progesterone have been ham- 

 pered by the requirement, in most instances, 

 for a previous stimulation of the tissue by 

 estrogen. The work of Wade and Jones 



(1956a, b) demonstrated an interesting ef- 

 fect of progesterone added in vitro on sev- 

 eral aspects of metabolism in rat liver mito- 

 chondria. Progesterone, but not estradiol, 

 testosterone, 17a-hydroxyprogesterone, or 

 any of several other steroids tested, stimu- 

 lated the adenosine triphosphatase activity 

 of rat liver mitochondria. This stimulation 

 is not the result of an increased permeability 

 of the mitochondrial membrane induced by 

 progesterone, for the stimulatory effect is 

 also demonstrable with mitochondria that 

 have been repeatedly frozen and thawed to 

 break the membranes. Other experiments 

 showed that ATP was the only substrate 

 effective in this system ; progesterone did not 

 activate the release of inorganic phosphate 

 from AMP, ADP, or glycerophosphate. 



In other experiments with rat liver mito- 

 chondria (Wade and Jones, 1956b), proges- 

 terone at a higher concentration (6 X lO"'* 

 m) was found to inhibit the utilization of 

 oxygen with one of the tricarboxylic acids 

 or with DPNH as substrate. This inhibition 

 is less specific and occurred with estradiol, 

 testosterone, pregnanediol, and 17a-hy- 

 droxy progesterone, as well as with proges- 

 terone. The inhibition of respiration by high 

 concentrations of steroids in vitro has been 

 reported many times and with several dif- 

 ferent tissues; it seems to be relatively un- 

 specific. Wade and Jones were able to show 

 that progesterone inhibits the reduction of 

 cytochrome c but accelerates the oxidation 

 of ascorbic acid. They concluded that pro- 

 gesterone may perhaps uncouple oxidation 

 from phosphorylation in a manner similar 

 to that postulated for dinitrophenol. The 

 site of action of this uncoupling appears to 

 be in the oxidation-reduction path between 

 DPNH and cytochrome c. Mueller (1953) 

 found that progesterone added in vitro de- 

 creases the incorporation of glycine-2-C^'* 

 into the protein of strips of rat uterus, thus 

 counteracting the stimulatory effect of es- 

 tradiol administered in vivo. 



Zander (1958) reported that A4-3-keto- 

 pregnene-20-a-ol and A4-3-ketopregnene- 

 20-^-ol arc effective gestational hormones 

 in the mouse, rabbit, and man, although 

 somewhat less active in general than is 

 progesterone. An enzyme in rat ovary which 

 converts progesterone to pregnene-20-a-ol, 

 and also catalyzes the reverse reaction, was 



