PHYSIOLOGY OF GONADS 



introduction of an OH group on the steroid 

 nucleus are usually called "hydroxylations." 

 Specific hydroxylases for the introduction 

 of an OH group at carbons 11, 16, 17, 21, 18, 

 and 19 have been demonstrated. All of these 

 require molecular oxygen and a reduced 

 pyridine nucleotide, usually TPNH. The 

 ll-/3-hydroxylase of the adrenal cortex has 

 been shown to be located in the mitochon- 

 dria (Hayano and Dorfman, 1953) . Experi- 

 ments with this enzyme system, utilizing 

 oxygen 18, showed that the oxygen atoms 

 are derived from gaseous oxygen and not 

 from the oxygen in the water molecules 

 (Hayano, Lindberg, Dorfman, Hancock and 

 Doering, 1955). Thus this hydroxylation re- 

 action also involves the reduction of molec- 

 ular oxygen. 



The oxidative cleavage of the side chains 

 of the steroid molecule appears to involve 

 similar hydroxylation reactions. The experi- 

 ments of Solomon, Levitan and Lieberman 

 (1956) indicate that the conversion of cho- 

 lesterol to pregnenolone involves one and 

 possibly two of these hydroxylation reac- 

 tions, with the introduction of OH groups 

 at carbons 20 and 22 before the splitting off 

 of the isocaproic acid. 



In summary, this newer knowledge of the 

 biosynthetic paths of steroids has revealed 

 that the differences between the several 

 steroid-secreting glands are largely quanti- 

 tative rather than qualitative. The testis, 

 for example, produces progesterone and 

 estrogens in addition to testosterone. The 

 change from the secretion of estradiol by 

 the follicle to the secretion of progesterone 

 by the corpus luteum can be understood as 

 a relative loss of activity of an enzyme in 

 the path between progesterone and estradiol. 

 If, for example, the enzyme for the 17-hy- 

 droxylation of progesterone became inactive 

 as the follicle cells are changed into the 

 corpus luteum, progesterone rather than 

 estradiol would subsequently be produced. 



Knowledge of these pathways also pro- 

 vides an explanation for certain abnormal 

 changes in the functioning of the glands. 

 Bongiovnnni (1953) and Jailer (1953) 

 showed that the adrenogenital syndrome 

 results from a loss of an enzyme or enzymes 

 for the hydroxylation reactions at carbons 

 21 and 11 of progesterone, which results in 

 an impairment in the production of Cortisol. 



The pituitary, with little or no Cortisol to 

 inhibit the secretion of adrenocorticotrophic 

 hormone (ACTH), produces an excess of 

 this hormone which stimulates the adrenal 

 to produce more steroids. There is an ex- 

 cretion of the metabolites of progesterone 

 and 17-hydroxy progesterone, pregnanediol 

 and pregnanetriol respectively, but some of 

 the 17-hydroxy progesterone is converted to 

 androgens and is secreted in increased 

 amount. 



G. CATABOLISM OF STEROmS 



Many of the steroid hormones are known 

 to act on the pituitary to suppress its se- 

 cretion of the appropriate trophic hormone, 

 ACTH, the follicle-stimulating hormone 

 (FSH), or luteinizing hormone (LH). It 

 would seem that the maintenance of the 

 proper feedback mechanism between ster- 

 oid-secreting gland and pituitary requires 

 that the steroids be continuously inactivated 

 and catabolized. The catabolic reactions of 

 the steroids are in general reductive in na- 

 ture and involve the reduction of ketonic 

 groups and the hydrogenation of double 

 bonds. The reduction of a ketonic group to 

 an OH group can lead to the production of 

 two different stereoisomers. If the OH group 

 projects from the steroid nucleus on the 

 same side as the angular methyl groups 

 at carbon 18 and carbon 19, i.e., above the 

 plane of the four rings, it is said to have 

 the yS-configuration and is represented by a 

 heavy line. If the OH projects on the op- 

 posite side of the steroid nucleus, below 

 the plane of the four rings, it is said to 

 have the a-configuration and is represented 

 by a dotted line. Although both isomers are 

 possible, usually one is formed to a much 

 greater extent than the other. 



The first catabolic step is usually the 

 reduction of the A4-3-ketone group of ring 

 A, usually to 3aOH compounds with the 

 hydrogen at carbon 5 attached in the /3- 

 configuration. The 5/3-configuration repre- 

 sents the CIS configuration of rings A and B. 

 The elimination of the A4-3-ketone group 

 greatly decreases the biologic activity of 

 the steroid and increases somewhat its solu- 

 bility in water. This reductive process oc- 

 curs largely in the liver. Progesterone is 

 converted by reduction of its A4-3-ketone 

 group to pregnane-3a:20a-diol, and 17-hy- 



