CH3C0-SC0A 



STEROID SEX HORMONES 



SCoA 



645 



CH^CO-SCoA 



Acetyl CoA 



CH3COCH2CO~SCoA 



Acetoacetyl CoA 



Sesquiterpene 

 (15C) 



COOH 



► HO— C— CH- 

 I ^ 



CO-' SCO A 



pOH-p methyl- 

 glutaric acyl Co A 



CHg 



C-CH- 

 I 



CH 

 II 

 CHo 



Isoprene unit 

 (5C) 



CHO 



I 



CHo 

 I ^ 



HO-C-CH^ 

 1 3 



CHo 

 I 2 

 COOH 



Mevalonic acid 



Squalene Lanosterol Cholesterol 



(30C) (30C) (27C) 



Fig. 11.1. Biogenesis of cholesterol. 



ter is dehydrogenated in ring A by the 

 enzyme 3-^-ol dehydrogenase and a spon- 

 taneous shift of the double bond from the 

 A5 , 6 to the A4 , 5 position results in proges- 

 terone. Progesterone undergoes successive 

 hydroxylation reactions, which require mo- 

 lecular oxygen and reduced triphospho- 

 pyridine nucleotide (TPNH), at carbons 17, 

 21, and 11. These hydroxylations yield, 

 in succession, 17-a-hydroxy progesterone, 

 Reichstein's compound S (ll-desoxy-17-hy- 

 droxycorticosterone), and Cortisol (17-a-hy- 

 droxvcorticosterone) . 



C. ANDROGENS 



17-a-Hydroxy progesterone is also the im- 

 mediate precursor of androgens and estro- 

 gens. Oxidative cleavage of its side chain 

 yields A-4-androstenedione, which under- 

 goes reduction to testosterone (Fig. 11.2). 

 A-4-Androstenedione may be hydroxylated 

 at carbon 11 to yield ll-/3-hydroxy-A-4- 

 androstenedione, which is an androgen iso- 

 lated from human urine. It has also been 

 found as a metabolite of certain androgenic 

 tumors of the adrenal cortex. 



