GREGORY PINCUS 



as well as of certain phases of carbohydrate metabolism in vivo. The 

 remarkable effects of steroid hormones on pituitary activity have led 

 to new conceptions of hormonal balance. The combination of bril- 

 liant chemical investigation and the astute application of chemical 

 discoveries to physiological investigation has been so prolific that the 

 journals are crowded with papers in the field; and in fact new journals 

 have been founded specifically for the publication of data in endocri- 

 nology. 



Nonetheless, on the biochemical side there have been two 

 notable gaps in the development of steroid hormone investigation: 



(1) the nature of steroid hormone anabolism and catabolism and 



(2) the role of the steroid hormones in cellular processes. 



Biosynthesis of Steroid Hormones 



Concerning the precursors and synthesis of the steroid hormones, 

 our factual basis is slight. Several authors have indicated possible 

 modes of degradation of cholesterol in vivo to active hormonal sub- 

 stance (3,6), and the synthesis of testosterone and progesterone is 

 indeed accomplished commercially in a series of reactions the first step 

 of which is the oxidation of the Cn side chain of cholesterol followed 

 by molecular rearrangement. Experimental verification of such 

 hypotheses was practically completely lacking until Bloch's recent 

 demonstration that deuterium-containing pregnanediol is found in 

 the urine of pregnancy after the administration of cholesterol contain- 

 ing heavy hydrogen. The recovery of marked pregnanediol was of 

 the order expected on the assumption that it arose from progesterone, 

 which in turn was synthesized from the cholesterol administered. The 

 nature of this cholesterol degradation and the probable intermediates 

 are not known, although Pearlman's isolation of a series of interesting 

 neutral steroids from bile suggests that a search in bile for the inter- 

 mediates may be profitable. Also suggestive is the evidence of Long 

 and his collaborators that cholesterol in the adrenal glands declines 

 markedly under conditions involving active secretion of corticosteroid. 

 It must still be demonstrated to what extent cholesterol is the precursor 

 of any or all steroid hormones. The evidence that cholesterol itself 

 is synthesized from simple precursors such as acetic acid renders un- 

 tenable the numerous theories concerning elementary steroid syn- 



306 



