STF.ROin HORMONES 



Since the inactivation of estradiol by rat liver slices appears to depend 

 on adequate supplies of thiamin and riboflavin, an approach to the 

 inactivating systems through enzymes dependent on these vitamins is 

 indicated. 



It is fairly well established that the liver is largely responsible 

 for the conversions: estradiol ^ estrone — > estriol. Liver perfusion 

 not only results in a rapid interconversion of estradiol and estrone, but 

 seems also to hasten the production of estriol. In contrast, estriol is 

 produced in negligible amounts after perfusion of the kidney with 

 estrone. Marrian (8) has suggested that folliculoid breakdown pro- 

 ceeds through estriol to a diketone, thence to other inactive substances. 

 Since the liver is such an active producer of estriol, the postulated 

 diketone should be sought in liver extracts, particularly after the 

 administration of natural folliculoid or following the incubation of the 

 hormones with liver slices or mash. 



OH 



/X/\ 



-OH 



O 



/X/X 



=o 



HO- 



Estriol 



HO— l^ 



Estratriene-3-ol-16,17-dione 



While the catabolic role of the liver has been most intensively 

 examined in studies with the folliculoids, its responsibility for the 

 breakdown of testosterone and progesterone is also established. It is 

 sufficient merely to implant pellets of these hormones into the hepatic 

 portal system (intrasplenic implantation is used principally) to observe 

 the remarkable absence of testoid or luteoid effects. Implantations 

 elsewhere are clearly effective. In contrast, the administration of 

 these steroids to partially hepatectomized animals results in remarkable 

 exaggeration of their typical effects. 



The nature of the products which the liver produces from these 

 hormones is not too well established. Recent work indicates that 

 testosterone is converted to a mixture of 17-ketosteroids one of which, 

 A*-androstene-3,17-dione, has been identified chemically. 



In contrast to the information available for the foUiculoid, 

 testoid, and luteoid hormones, practically nothing is known about the 



315 



