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JAMES K. GRANT
from the urine of human subjects indicated a species difference. However the isolation of a 6a-hydroxy compound on incubation of androstenedione with ox adrenal homogenates (122) and the isolation of
both 6a- and ββ-hydroxy derivatives of llß-hydroxyandrostenedione
from the urine of guinea pigs (145) suggest that these are general
reactions.
The general impression that species may differ in their ability to
effect the reduction of the 20-oxo group to either the 20a- or 20/2hydroxy group in a wide variety of C 2 i steroids has been supported
by recent work. Thus the rat gives predominantly the 20ß-epimer in
vivo (146) and in vitro (147). In man the 20a-epimer is the more usual
product in vivo (148) and in vitro (149). In this respect the rabbit appears to be similar to man (150). The guinea pig however excretes both
20a- and 20/?-hydroxy derivatives of hydrocortisone (145).
Studies of the metabolism of such C 2 i steroids as progesterone,
hydrocortisone, and 11-deoxycorticosterone in vivo have been made
mostly with human subjects and have indicated that the reduced substances formed are predominantly of the 5/?-pregnane series. In vitro
studies have, however, usually been made with tissues from the rat or
the ox, and the reduced steroids formed are predominantly 5a-pregnane
derivatives. It is not yet possible to decide if this is due to a species
difference or to some other cause. Using a sensitive specific test for 5ßpregnane-3a,20a-diol, this substance was not detected in the urine of
rats injected with progesterone (151). In a single experiment in which
progesterone was incubated with liver from a human subject 5ßpregnane derivatives were predominant among the products (149).
In no species is the nature of the estrogenic steroids secreted by the
endocrine tissues known. Thus we are unable to say whether the
common estrogens, estrone, estradiol-17a, and estradiol-17ß are hormones or metabolites. Because it is most active in some biological tests
estradiol-17/3 has been regarded as the ovarian hormone in man. From
what is known of the biosynthesis of estrogenic steroids (see p. 181) it
would be more reasonable to regard the 17-ketosteroid estrone as the
primary substance formed. The interconversion of estrone and estradiol17/? by a variety of tissues from human subjects and animals is well
established (152) and could account for the appearance of both these
substances in the urine. Species differences, however, appear to exist
in the stereochemical direction of the reduction of estrone. Thus estradiol-17/? but not 17a is found in the urine in man, whereas the urine of
pregnant cows (153) and goats (154) contains the 17a-epimer but no
detectable amounts of the 17/?-epimer. The formation of the 17a-epimer
seems also to be favored in rabbit tissues (155). Velle takes the view
JAMES K. GRANT
from the urine of human subjects indicated a species difference. However the isolation of a 6a-hydroxy compound on incubation of androstenedione with ox adrenal homogenates (122) and the isolation of
both 6a- and ββ-hydroxy derivatives of llß-hydroxyandrostenedione
from the urine of guinea pigs (145) suggest that these are general
reactions.
The general impression that species may differ in their ability to
effect the reduction of the 20-oxo group to either the 20a- or 20/2hydroxy group in a wide variety of C 2 i steroids has been supported
by recent work. Thus the rat gives predominantly the 20ß-epimer in
vivo (146) and in vitro (147). In man the 20a-epimer is the more usual
product in vivo (148) and in vitro (149). In this respect the rabbit appears to be similar to man (150). The guinea pig however excretes both
20a- and 20/?-hydroxy derivatives of hydrocortisone (145).
Studies of the metabolism of such C 2 i steroids as progesterone,
hydrocortisone, and 11-deoxycorticosterone in vivo have been made
mostly with human subjects and have indicated that the reduced substances formed are predominantly of the 5/?-pregnane series. In vitro
studies have, however, usually been made with tissues from the rat or
the ox, and the reduced steroids formed are predominantly 5a-pregnane
derivatives. It is not yet possible to decide if this is due to a species
difference or to some other cause. Using a sensitive specific test for 5ßpregnane-3a,20a-diol, this substance was not detected in the urine of
rats injected with progesterone (151). In a single experiment in which
progesterone was incubated with liver from a human subject 5ßpregnane derivatives were predominant among the products (149).
In no species is the nature of the estrogenic steroids secreted by the
endocrine tissues known. Thus we are unable to say whether the
common estrogens, estrone, estradiol-17a, and estradiol-17ß are hormones or metabolites. Because it is most active in some biological tests
estradiol-17/3 has been regarded as the ovarian hormone in man. From
what is known of the biosynthesis of estrogenic steroids (see p. 181) it
would be more reasonable to regard the 17-ketosteroid estrone as the
primary substance formed. The interconversion of estrone and estradiol17/? by a variety of tissues from human subjects and animals is well
established (152) and could account for the appearance of both these
substances in the urine. Species differences, however, appear to exist
in the stereochemical direction of the reduction of estrone. Thus estradiol-17/? but not 17a is found in the urine in man, whereas the urine of
pregnant cows (153) and goats (154) contains the 17a-epimer but no
detectable amounts of the 17/?-epimer. The formation of the 17a-epimer
seems also to be favored in rabbit tissues (155). Velle takes the view