294
8 Peptide Hormones
the skin of the toad Bombina bombina (see
Fig. 9.2, p. 324), which arises from a 107-aminoacid precursor, has a C-terminal structure similar
to that of tachykinin. This peptide stimulates the
secretion of gastrin and other gastrointestinal hormones in mammals; the gastrin-releasing peptide
(GRP) isolated from the gut of man and other
mammals is identical to bombesin in 9 out of 10
C-terminal amino acids [181]. A peptide similar to
mammalian GRP has been isolated from the
brain of the frog Rana ridibunda [42]. Bombesinlike peptides with species-specific sequences are
known from the skin of other anurans (see
Fig. 9.2). Neurotensin (NT) (Fig. 8.2f) was discovered in bovine hypothalamus, but is also found
in the alimentary canal. NT and the NT-like neuromedin N (six amino acids) stimulate gut contractions. Both arise from a common large precursor of 170 amino acids [31] and are already
detectable in the chicken. Xenopsin (see
Fig.9.2), found in the skin of the clawed frog
Xenopus laevis, is very similar to NT in its Cterminal sequence. Altogether, more than 40 different peptides have been detected in Xenopus
skin, including the xenopsin-like levitide, a further peptide identical to the mammalian TRF,
and caerulein (Fig.8.2i), which belongs to the
gastrin-cholecystokinin family but is considered
here because of its location. The presence of a
further peptide (PYLa) of unknown biological significance was postulated on the basis of cDNA
analysis; so far it has been isolated only in a shortened form, PGU [80, 172]. The xenopsin precursor has a length of 80 amino acids and carries the
sequence of the octapeptide at its C-terminus; its
sequence agrees up to 86% with the levitide precursor and to 54 % with that of physalaemin
[172]. There are at least three caerulein precursors in Xenopus skin, and these are classified,
according to the number of caerulein sequences
they contain, into types I, III and IY.1YPes I and
III are encoded by different genes, both of which
have eight exons. The sequence of the decapeptide caerulein is encoded in small 45-bp exons. In
the gene of type I, one caerulein-encoding exon
is replaced by a coding sequence for a novel peptide that appears to have only six amino acids
(60 %) in common with caerulein but has not yet
been isolated [180,225]. The other peptides
detectable in Xenopus skin apparently arise from
the precursors of TRF, xenopsin, PGL a and caerulein by cleavage at single arginine or lysine residues [70]. An endoprotease specific for the
sequence - RXVRG - has been isolated from
Xenopus skin [112].
8.2.3 Hormones of the Urophysis
In addition to the hypothalamus-hypophysis sys. tern, the bony fish have a further neurosecretory
region in the bone marrow of the tail, the urophysis, which produces several hormonal factors
known as urotensins. Urotensin I (Fig. 8.2 g) is
41 amino acids long and significantly homologous
to the mammalian CRF. Urotensin II (Fig.8.2h)
shows some similarity in its 12 amino acids to
SST-14 and appears in the fish in several forms
[86].
8.3 Hormones of the Adenohypophysis
8.3.1 Glycoproteins of the Adenohypophysis
Lutropin (LH), follitropin (FSH) and thyrotropin
(TSH) of the hypophysis, and choriongonadotropin (CG) of the placenta are all glycoproteins of
about 30 kDa made up of an a and a fl chain. The
a chains of all hormones in a species are identical, or at least very similar, whilst the fl chains
responsible for the hormone activity are homologous but quite variable. The a-chain sequences
of different mammals differ in only 2-5 % of their
96 amino acids, and compared with those of the
teleosts by only 30-35% [9,87,126]. The chum
salmon Oncorhyncus keta is so far the only vertebrate known to have two different a chains (in
gonadotropin I). The two chains are only 72 %
similar, which is little more than the similarity to
the bovine a chain [87]. Although the rate of
evolution of the fl chains is significantly higher
than that of the a chains, the species-specific differences of the fl chains of a particular hormone
are much less than the sequence differences
between the fl chains of different hormones in
one species. Thus, in humans, almost all pairwise
comparisons of fl chains give merely 30-40 %
identical amino acids; only the ~ chains of LH
and CG agree by 80 %. In contrast, the sequence
.similarity of the LH fl chains from the sperm
whale and swine is 90 %, from the dog and rat is
89 %, and from the sperm whale and man is
70 %; the human and equine CG fl chains agree
by 66 % [166,213,236]. The a and fl chains of
different species can combine to give biologically
active hybrid molecules, independently of the
normal specificity of the fl subunit [187]. The car-
8 Peptide Hormones
the skin of the toad Bombina bombina (see
Fig. 9.2, p. 324), which arises from a 107-aminoacid precursor, has a C-terminal structure similar
to that of tachykinin. This peptide stimulates the
secretion of gastrin and other gastrointestinal hormones in mammals; the gastrin-releasing peptide
(GRP) isolated from the gut of man and other
mammals is identical to bombesin in 9 out of 10
C-terminal amino acids [181]. A peptide similar to
mammalian GRP has been isolated from the
brain of the frog Rana ridibunda [42]. Bombesinlike peptides with species-specific sequences are
known from the skin of other anurans (see
Fig. 9.2). Neurotensin (NT) (Fig. 8.2f) was discovered in bovine hypothalamus, but is also found
in the alimentary canal. NT and the NT-like neuromedin N (six amino acids) stimulate gut contractions. Both arise from a common large precursor of 170 amino acids [31] and are already
detectable in the chicken. Xenopsin (see
Fig.9.2), found in the skin of the clawed frog
Xenopus laevis, is very similar to NT in its Cterminal sequence. Altogether, more than 40 different peptides have been detected in Xenopus
skin, including the xenopsin-like levitide, a further peptide identical to the mammalian TRF,
and caerulein (Fig.8.2i), which belongs to the
gastrin-cholecystokinin family but is considered
here because of its location. The presence of a
further peptide (PYLa) of unknown biological significance was postulated on the basis of cDNA
analysis; so far it has been isolated only in a shortened form, PGU [80, 172]. The xenopsin precursor has a length of 80 amino acids and carries the
sequence of the octapeptide at its C-terminus; its
sequence agrees up to 86% with the levitide precursor and to 54 % with that of physalaemin
[172]. There are at least three caerulein precursors in Xenopus skin, and these are classified,
according to the number of caerulein sequences
they contain, into types I, III and IY.1YPes I and
III are encoded by different genes, both of which
have eight exons. The sequence of the decapeptide caerulein is encoded in small 45-bp exons. In
the gene of type I, one caerulein-encoding exon
is replaced by a coding sequence for a novel peptide that appears to have only six amino acids
(60 %) in common with caerulein but has not yet
been isolated [180,225]. The other peptides
detectable in Xenopus skin apparently arise from
the precursors of TRF, xenopsin, PGL a and caerulein by cleavage at single arginine or lysine residues [70]. An endoprotease specific for the
sequence - RXVRG - has been isolated from
Xenopus skin [112].
8.2.3 Hormones of the Urophysis
In addition to the hypothalamus-hypophysis sys. tern, the bony fish have a further neurosecretory
region in the bone marrow of the tail, the urophysis, which produces several hormonal factors
known as urotensins. Urotensin I (Fig. 8.2 g) is
41 amino acids long and significantly homologous
to the mammalian CRF. Urotensin II (Fig.8.2h)
shows some similarity in its 12 amino acids to
SST-14 and appears in the fish in several forms
[86].
8.3 Hormones of the Adenohypophysis
8.3.1 Glycoproteins of the Adenohypophysis
Lutropin (LH), follitropin (FSH) and thyrotropin
(TSH) of the hypophysis, and choriongonadotropin (CG) of the placenta are all glycoproteins of
about 30 kDa made up of an a and a fl chain. The
a chains of all hormones in a species are identical, or at least very similar, whilst the fl chains
responsible for the hormone activity are homologous but quite variable. The a-chain sequences
of different mammals differ in only 2-5 % of their
96 amino acids, and compared with those of the
teleosts by only 30-35% [9,87,126]. The chum
salmon Oncorhyncus keta is so far the only vertebrate known to have two different a chains (in
gonadotropin I). The two chains are only 72 %
similar, which is little more than the similarity to
the bovine a chain [87]. Although the rate of
evolution of the fl chains is significantly higher
than that of the a chains, the species-specific differences of the fl chains of a particular hormone
are much less than the sequence differences
between the fl chains of different hormones in
one species. Thus, in humans, almost all pairwise
comparisons of fl chains give merely 30-40 %
identical amino acids; only the ~ chains of LH
and CG agree by 80 %. In contrast, the sequence
.similarity of the LH fl chains from the sperm
whale and swine is 90 %, from the dog and rat is
89 %, and from the sperm whale and man is
70 %; the human and equine CG fl chains agree
by 66 % [166,213,236]. The a and fl chains of
different species can combine to give biologically
active hybrid molecules, independently of the
normal specificity of the fl subunit [187]. The car-