652
16 Sterols and Steroids
be that the calciferol metabolites are involved in
calcium homeostasis, maintaining, for example,
the calcium concentration in the blood plasma of
the shark at a level one-third that of the surrounding seawater. At a concentration of 20-80 I-tg/l,
25-hydroxycalciferol is the major component in
the blood plasma of all birds and mammals examined; this is followed by calciferol, 24,25- and
25,26-dihydroxycalciferol at 1-10 I-tg/l. The concentration of 1a,25-dihydroxycalciferol is one
order of magnitude lower at 0.02-0.06 I-tg/l. Cholecalciferol (vitamin D3) and its metabolites are
almost always found at concentrations 20- to 100fold higher than those of ergocalciferol (vitamin D2); the sheep appears to be an exception in
which the concentrations are more-or-Iess equal
[83]. Cholecalciferol and ergocalciferol are
equally effective in humans, Old World apes, cattle and rats. In the New World apes, cholecalciferol is clearly superior and must be considered to
be the active substance in all other vertebrates;
for example, it is 100-fold more effective than
ergocalciferol in the chicken. In agreement
with this is the observation that 25-hydroxyergocalciferol is less tightly bound than 25-cholecalciferol in the blood plasma of fish, reptiles,
birds and monotremes, but in the Placentalia
binding is more-or-Iess equal. The calciferol
metabolites in the blood plasma are bound to a
specific vitamin-D-binding protein (DBP). The
DBP of the mammals belong to the a-globulins;
these are monomeric glycoproteins of 51-55 kDa
with 1 % carbohydrate which, according to the Nand C-terminal sequences, constitute their own
protein family [93].
The two dihydroxycalciferols apparently have
different functions and are not completely interchangeable. Chickens or Japanese quails containing only 1a,25-dihydroxycalciferol have eggs that
develop normally but do not hatch; however, if
24,25-dihydroxycalciferol is added to the diet, the
hatching rate is the same as with calciferol itself.
Similarly, skeleton development in young chickens is normal only when both forms are available.
The two forms apparently affect different cell
populations of the bone. The osteoclasts, responsible for the absorption of bone and calcium
mobilization, are stimulated by 1a,25-dihydroxycalciferol, and the cartilage cells and osteoblasts, responsible for bone formation, are
stimulated by 24,25-dihydroxycalciferol. 1a,25Dihydroxycalciferol additionally stimulates gut
resorption of calcium and phosphate ions, as well
as calcium reabsorption in the kidney tubules. In
summary, 1a,25-dihydroxycalciferol appears to
be responsible in particular for calcium homeostasis, and 24,25-dihydroxycalciferol is responsible
for bone formation and mineralization [83].
Calciferol receptors are found at all active
sites, i.e. in the calcium-transporting cells of the
gut, kidney, bone and milk glands, and also in
hormone glands whose hormones influence calciferol hydroxlases, e.g. the parathyroid, hypophysis and pancreas. This distribution has been
shown in different mammals and birds, and also
in lower vertebrates such as the eel Anquilla
anquilla, where 1a,25-calciferol receptors have
been found in the gut, gills, hypophysis, Stannius
bodies, liver and brain, but not in the kidneys,
muscle or skin. Different receptors that are specific for 1a,25- or 24,25-dihydroxycalciferol have
been isolated from the parathyroid of the chicken
[83]. 1a,25-Dihydroxycalciferol receptors from
various mammals and the chicken have been
sequenced via the cDNA. They are polypeptides
of about 60 kDa that bind 1a,25-dihydroxycalciferol selectively with high affinity and
then interact with the DNA. The cysteine-rich
DNA-binding domains in particular are very similar to the corresponding regions of other steroid
receptors and the erb-A oncogene [13, 77].
The calciferol balance in the fish appears to
differ in several important respects from that in
the birds and mammals. Although the photochemical formation of cholecalciferol is hardly
significant, because of the UV-absorbing nature
of water, many fish nevertheless contain large
amounts of this substance, and are important
sources of calciferol. This is also true of the cartilaginous fish, in which the skeleton is not calcified. Fish blood plasma also contains a vitamin Dbinding a-globulin. Although fish liver, gut and
kidney have been shown to contain cytochrome
P-450, the liver microsomes do not produce polar
metabolites other than 25-hydroxycalciferol from
calciferol; the kidney metabolizes neither 25hydroxycalciferol nor calciferol [130]. It is not
clear whether 25- and la-hydroxylation are possible in invertebrates. There are earlier results
showing the formation of 25-hydroxycalciferol in
terrestrial snails, but the present conclusion is
that neither 25-hydroxycalciferol nor 1a,25dihydroxycalciferol have been unambiguously
demonstrated in either the gastropods, bivalves
or echinoids [70].
16 Sterols and Steroids
be that the calciferol metabolites are involved in
calcium homeostasis, maintaining, for example,
the calcium concentration in the blood plasma of
the shark at a level one-third that of the surrounding seawater. At a concentration of 20-80 I-tg/l,
25-hydroxycalciferol is the major component in
the blood plasma of all birds and mammals examined; this is followed by calciferol, 24,25- and
25,26-dihydroxycalciferol at 1-10 I-tg/l. The concentration of 1a,25-dihydroxycalciferol is one
order of magnitude lower at 0.02-0.06 I-tg/l. Cholecalciferol (vitamin D3) and its metabolites are
almost always found at concentrations 20- to 100fold higher than those of ergocalciferol (vitamin D2); the sheep appears to be an exception in
which the concentrations are more-or-Iess equal
[83]. Cholecalciferol and ergocalciferol are
equally effective in humans, Old World apes, cattle and rats. In the New World apes, cholecalciferol is clearly superior and must be considered to
be the active substance in all other vertebrates;
for example, it is 100-fold more effective than
ergocalciferol in the chicken. In agreement
with this is the observation that 25-hydroxyergocalciferol is less tightly bound than 25-cholecalciferol in the blood plasma of fish, reptiles,
birds and monotremes, but in the Placentalia
binding is more-or-Iess equal. The calciferol
metabolites in the blood plasma are bound to a
specific vitamin-D-binding protein (DBP). The
DBP of the mammals belong to the a-globulins;
these are monomeric glycoproteins of 51-55 kDa
with 1 % carbohydrate which, according to the Nand C-terminal sequences, constitute their own
protein family [93].
The two dihydroxycalciferols apparently have
different functions and are not completely interchangeable. Chickens or Japanese quails containing only 1a,25-dihydroxycalciferol have eggs that
develop normally but do not hatch; however, if
24,25-dihydroxycalciferol is added to the diet, the
hatching rate is the same as with calciferol itself.
Similarly, skeleton development in young chickens is normal only when both forms are available.
The two forms apparently affect different cell
populations of the bone. The osteoclasts, responsible for the absorption of bone and calcium
mobilization, are stimulated by 1a,25-dihydroxycalciferol, and the cartilage cells and osteoblasts, responsible for bone formation, are
stimulated by 24,25-dihydroxycalciferol. 1a,25Dihydroxycalciferol additionally stimulates gut
resorption of calcium and phosphate ions, as well
as calcium reabsorption in the kidney tubules. In
summary, 1a,25-dihydroxycalciferol appears to
be responsible in particular for calcium homeostasis, and 24,25-dihydroxycalciferol is responsible
for bone formation and mineralization [83].
Calciferol receptors are found at all active
sites, i.e. in the calcium-transporting cells of the
gut, kidney, bone and milk glands, and also in
hormone glands whose hormones influence calciferol hydroxlases, e.g. the parathyroid, hypophysis and pancreas. This distribution has been
shown in different mammals and birds, and also
in lower vertebrates such as the eel Anquilla
anquilla, where 1a,25-calciferol receptors have
been found in the gut, gills, hypophysis, Stannius
bodies, liver and brain, but not in the kidneys,
muscle or skin. Different receptors that are specific for 1a,25- or 24,25-dihydroxycalciferol have
been isolated from the parathyroid of the chicken
[83]. 1a,25-Dihydroxycalciferol receptors from
various mammals and the chicken have been
sequenced via the cDNA. They are polypeptides
of about 60 kDa that bind 1a,25-dihydroxycalciferol selectively with high affinity and
then interact with the DNA. The cysteine-rich
DNA-binding domains in particular are very similar to the corresponding regions of other steroid
receptors and the erb-A oncogene [13, 77].
The calciferol balance in the fish appears to
differ in several important respects from that in
the birds and mammals. Although the photochemical formation of cholecalciferol is hardly
significant, because of the UV-absorbing nature
of water, many fish nevertheless contain large
amounts of this substance, and are important
sources of calciferol. This is also true of the cartilaginous fish, in which the skeleton is not calcified. Fish blood plasma also contains a vitamin Dbinding a-globulin. Although fish liver, gut and
kidney have been shown to contain cytochrome
P-450, the liver microsomes do not produce polar
metabolites other than 25-hydroxycalciferol from
calciferol; the kidney metabolizes neither 25hydroxycalciferol nor calciferol [130]. It is not
clear whether 25- and la-hydroxylation are possible in invertebrates. There are earlier results
showing the formation of 25-hydroxycalciferol in
terrestrial snails, but the present conclusion is
that neither 25-hydroxycalciferol nor 1a,25dihydroxycalciferol have been unambiguously
demonstrated in either the gastropods, bivalves
or echinoids [70].