3. LIPIDS: STEROID METABOLISM
183
may not be significantly labeled, cholesterol at the site of estrogens
synthesis may be labeled and may in fact be the precursor of the
estrogens formed. Other workers (95, 96) have shown that various
preparations of ovaries from dogs, cats, and human subjects could incorporate acetate into cholesterol, estradiol-17/?, and estrone, and the
conversion of 4-C
14 -cholesterol to 4-C
14 -estrone in a pregnant woman
has been demonstrated (96).
One may conclude that in the dog, cat, horse, and man acetate and
cholesterol may act as precursors of estrone formed in the ovary and
possibly also in the case of the adrenal glands, placenta, and testes.
From in vitro studies it has been possible to construct a plausible
scheme for the biosynthesis of steroid estrogens from progesterone
(Fig. 4) which may be derived from acetate via cholesterol (97). It is
not known whether such a scheme does in fact operate or if it represents the only biosynthetic pathway for the formation of steroid
estrogens. Most of the individual reactions have been demonstrated by
means of endocrine tissues (including the placenta) obtained from man
and the ox. It is interesting to note that whereas cow placenta, follicular fluid, and adrenal tissue were able to transform 19-hydroxyandrost4-ene-3,17-dione into estrone, rabbit placenta was inactive (98).
c. Biosynthesis of Steroid Sex Hormones in the Placenta and Adrenal
Cortex. There is evidence that progesterone, androgens, and estrogens
may be elaborated by the placenta and adrenals in addition to the
gonads.
Since the ovaries may be removed from the pregnant mare, cow,
ewe, bitch, and woman without producing abortion it has been assumed
that the placentas of these species produce progesterone. In support of
this it has been shown that extracts of cow placenta produce progestational changes in the rabbit endometrium (99). It has not, however,
been possible to repeat this observation consistently (100), and Short
(101) using a sensitive chemical method found progesterone in the
placenta of the mare, but not in the cow, ewe, goat, or sow. The
placenta of human subjects is known to be a rich source of progesterone
and contains enzymes which catalyze the formation of progesterone
from pregnenolone (102). These observations suggest the existence of
a wide species difference in endocrine mechanisms responsible for the
maintenance of pregnancy.
Although it is probable that the placenta can elaborate estrogens, no
comparative studies have been made.
Biosynthesis of sex hormones in the adrenal cortex was referred to
in Section I,B,2,e.
183
may not be significantly labeled, cholesterol at the site of estrogens
synthesis may be labeled and may in fact be the precursor of the
estrogens formed. Other workers (95, 96) have shown that various
preparations of ovaries from dogs, cats, and human subjects could incorporate acetate into cholesterol, estradiol-17/?, and estrone, and the
conversion of 4-C
14 -cholesterol to 4-C
14 -estrone in a pregnant woman
has been demonstrated (96).
One may conclude that in the dog, cat, horse, and man acetate and
cholesterol may act as precursors of estrone formed in the ovary and
possibly also in the case of the adrenal glands, placenta, and testes.
From in vitro studies it has been possible to construct a plausible
scheme for the biosynthesis of steroid estrogens from progesterone
(Fig. 4) which may be derived from acetate via cholesterol (97). It is
not known whether such a scheme does in fact operate or if it represents the only biosynthetic pathway for the formation of steroid
estrogens. Most of the individual reactions have been demonstrated by
means of endocrine tissues (including the placenta) obtained from man
and the ox. It is interesting to note that whereas cow placenta, follicular fluid, and adrenal tissue were able to transform 19-hydroxyandrost4-ene-3,17-dione into estrone, rabbit placenta was inactive (98).
c. Biosynthesis of Steroid Sex Hormones in the Placenta and Adrenal
Cortex. There is evidence that progesterone, androgens, and estrogens
may be elaborated by the placenta and adrenals in addition to the
gonads.
Since the ovaries may be removed from the pregnant mare, cow,
ewe, bitch, and woman without producing abortion it has been assumed
that the placentas of these species produce progesterone. In support of
this it has been shown that extracts of cow placenta produce progestational changes in the rabbit endometrium (99). It has not, however,
been possible to repeat this observation consistently (100), and Short
(101) using a sensitive chemical method found progesterone in the
placenta of the mare, but not in the cow, ewe, goat, or sow. The
placenta of human subjects is known to be a rich source of progesterone
and contains enzymes which catalyze the formation of progesterone
from pregnenolone (102). These observations suggest the existence of
a wide species difference in endocrine mechanisms responsible for the
maintenance of pregnancy.
Although it is probable that the placenta can elaborate estrogens, no
comparative studies have been made.
Biosynthesis of sex hormones in the adrenal cortex was referred to
in Section I,B,2,e.