dusinae, and these peptides have the highest
known morphine-like activity. They include the !!receptor-specific dermorphin (Tyr-D-Ala-PheGly-Tyr-Pro-Ser-Nh2) and the o-receptor-specific
dermencephalins and deltorphins, which all carry
a D-Ala or D-Met residue in position 2. In the
mRNAs of the longer precursors, however, the
corresponding positions have the co dons GCG or
AUG, coding for L-Ala or L-Met; frog brain contains in addition to the 2-D-Met dermencephalin
the corresponding L-Met compound, in fact at a
l00-fold higher concentration. The D-amino acid
residues apparently arise by post-translational
processing of the precursor via an incompletely
described isomerization reaction of low efficiency
[143].
8.3.4 Growth Hormone, Prolactin
and Lactogen
The growth hormone somatotropin (GH) and
prolactin (PRL) from the adenohypophysis together with lactogen (LS) or chorionsomatomammotropin from the placenta belong to the same
hormone family. GH is present in all vertebrates,
with the possible exception of the agnathans, and
is consistently involved in growth regulation. In
contrast, the equally widely found PRL has very
varied functions, from osmoregulation in the teleosts to control of lactation in mammals. The role
of PRL in birds is not yet clear; in the pigeon it
stimulates production of crop milk [228].
The growth hormones, whose amino acid
sequences have been determined directly or via
cDNA or gene sequences in all classes of vertebrates, are very variable. The GH genes of most
vertebrates, including the carp Cyprinus carpio,
consist of five exons; in Salmo gairdneri and S. salar there are six exons [36, 90]. GH varies in
length, e.g. within the mammals from 178 to
196 amino acids; the smallest GH, with only
173 residues, is found in the flounder Paralichthys
olivaceus [142]. The similarity of the amino acid
sequences correlates with the extent of the phylogenetic relationships. For mammalian GHs,
between 98 % (primates) and 66 % (human/sei
whale) identical amino acids are found. Comparisons with the GH of the sea turtle Chelonia midas
gave the following percentage similarities:
chicken 89 % , rat 79 %, bullfrog Rana catesbeiana
69 %, blue shark Prionace glauca 68 %, and eel
58 % ; for the chum salmon Oncorhyncus keta it is
only 40 %. Differences in GH sequences are
greatest within the teleosts; compared with the
8.4.1 The Gastrin-Cholecystokinin Family
297
carp Cyprinus carpio, the salmon Salmo salar
shows 66 % agreement, but the yellow tail Seriola
quinqueradiata shows only 49 % [36, 105,242].
The PRL sequences vary within and between
vertebrate classes to an extent similar to that of
the GH sequences. Relative to the turtle Chelonia midas, one finds 86 % identical amino acids in
the chicken, 81 % in the horse, pig and fin whale,
75-71 % in cattle, sheep and humans, 60-56 % in
the mouse and rat, and only 35-31 % in various
fish species [94, 228, 243]. Further members of
the GHlPRL family have been discovered in the
hypophyses of the Atlantic cod Gadus morrhua
and the flounder Paralichthys olivaceus; these are
21-27 % similar to the GH and PRL of the teleosts and are therefore referred to as somatolactins
[178]. The GHlPRL family also includes peptide
hormones produced in the placenta. The placental lactogen (PL), which stimulates milk synthesis, has so far been detected in primates, Artiodactyla, Lagomorpha and Rodentia; it is by no
means certain that it is universal in the Placentalia. The bovine hormone is very different from
that of all other species, e.g. with a molecular
mass of 32 kDa it is much larger than the rest
(20-22 kDa). Whereas human PL has 85 %
sequence agreement with human GH, bovine PL
is more similar to PRL than to GH (51 % agreement as against 20 % ). The similarity of bovine
and human PL is only 20 %, but compared with
placental hormones of the rodents it is about
30 % [196]. Further PRL-like placental proteins have been detected in cattle, mice and rats
[239].
8.4 Hormones of the Stomach, Intestine
and Pancreas
8.4.1 The Gastrin-Cholecystokinin Family
The peptides gastrin and cholecystokinen (CKK)
from the alimentary canal, together with caerulein from frog skin, may be considered homologous based upon the agreements shown by their Cterminal sequences (Fig. 8.2i). As the precursors
can be cleaved at various positions, there exist
gastrins and cholecystokinins with N-terminal
regions of different length: gastrin-34, -17 and
-14; and CKK-58, -39, -33, -22 and -8. The
sequence - YMGWMDF - is sufficient for binding to the CKK receptor; the gastrins contain the
known morphine-like activity. They include the !!receptor-specific dermorphin (Tyr-D-Ala-PheGly-Tyr-Pro-Ser-Nh2) and the o-receptor-specific
dermencephalins and deltorphins, which all carry
a D-Ala or D-Met residue in position 2. In the
mRNAs of the longer precursors, however, the
corresponding positions have the co dons GCG or
AUG, coding for L-Ala or L-Met; frog brain contains in addition to the 2-D-Met dermencephalin
the corresponding L-Met compound, in fact at a
l00-fold higher concentration. The D-amino acid
residues apparently arise by post-translational
processing of the precursor via an incompletely
described isomerization reaction of low efficiency
[143].
8.3.4 Growth Hormone, Prolactin
and Lactogen
The growth hormone somatotropin (GH) and
prolactin (PRL) from the adenohypophysis together with lactogen (LS) or chorionsomatomammotropin from the placenta belong to the same
hormone family. GH is present in all vertebrates,
with the possible exception of the agnathans, and
is consistently involved in growth regulation. In
contrast, the equally widely found PRL has very
varied functions, from osmoregulation in the teleosts to control of lactation in mammals. The role
of PRL in birds is not yet clear; in the pigeon it
stimulates production of crop milk [228].
The growth hormones, whose amino acid
sequences have been determined directly or via
cDNA or gene sequences in all classes of vertebrates, are very variable. The GH genes of most
vertebrates, including the carp Cyprinus carpio,
consist of five exons; in Salmo gairdneri and S. salar there are six exons [36, 90]. GH varies in
length, e.g. within the mammals from 178 to
196 amino acids; the smallest GH, with only
173 residues, is found in the flounder Paralichthys
olivaceus [142]. The similarity of the amino acid
sequences correlates with the extent of the phylogenetic relationships. For mammalian GHs,
between 98 % (primates) and 66 % (human/sei
whale) identical amino acids are found. Comparisons with the GH of the sea turtle Chelonia midas
gave the following percentage similarities:
chicken 89 % , rat 79 %, bullfrog Rana catesbeiana
69 %, blue shark Prionace glauca 68 %, and eel
58 % ; for the chum salmon Oncorhyncus keta it is
only 40 %. Differences in GH sequences are
greatest within the teleosts; compared with the
8.4.1 The Gastrin-Cholecystokinin Family
297
carp Cyprinus carpio, the salmon Salmo salar
shows 66 % agreement, but the yellow tail Seriola
quinqueradiata shows only 49 % [36, 105,242].
The PRL sequences vary within and between
vertebrate classes to an extent similar to that of
the GH sequences. Relative to the turtle Chelonia midas, one finds 86 % identical amino acids in
the chicken, 81 % in the horse, pig and fin whale,
75-71 % in cattle, sheep and humans, 60-56 % in
the mouse and rat, and only 35-31 % in various
fish species [94, 228, 243]. Further members of
the GHlPRL family have been discovered in the
hypophyses of the Atlantic cod Gadus morrhua
and the flounder Paralichthys olivaceus; these are
21-27 % similar to the GH and PRL of the teleosts and are therefore referred to as somatolactins
[178]. The GHlPRL family also includes peptide
hormones produced in the placenta. The placental lactogen (PL), which stimulates milk synthesis, has so far been detected in primates, Artiodactyla, Lagomorpha and Rodentia; it is by no
means certain that it is universal in the Placentalia. The bovine hormone is very different from
that of all other species, e.g. with a molecular
mass of 32 kDa it is much larger than the rest
(20-22 kDa). Whereas human PL has 85 %
sequence agreement with human GH, bovine PL
is more similar to PRL than to GH (51 % agreement as against 20 % ). The similarity of bovine
and human PL is only 20 %, but compared with
placental hormones of the rodents it is about
30 % [196]. Further PRL-like placental proteins have been detected in cattle, mice and rats
[239].
8.4 Hormones of the Stomach, Intestine
and Pancreas
8.4.1 The Gastrin-Cholecystokinin Family
The peptides gastrin and cholecystokinen (CKK)
from the alimentary canal, together with caerulein from frog skin, may be considered homologous based upon the agreements shown by their Cterminal sequences (Fig. 8.2i). As the precursors
can be cleaved at various positions, there exist
gastrins and cholecystokinins with N-terminal
regions of different length: gastrin-34, -17 and
-14; and CKK-58, -39, -33, -22 and -8. The
sequence - YMGWMDF - is sufficient for binding to the CKK receptor; the gastrins contain the