bohydrate content of the hormones varies widely,
e.g. from 16 % in bovine LH to 45 % in equine
CG.
The amphibians, turtles, crocodiles, birds and
mammals produce two different gonadotropins
(GTH): FSH and LH. There is apparently only
one GTH present in lizards and snakes, and this is
immunologically distinct from mammalian FSH
but has no LH activity. On the other hand, sheep
FSH is immunologically cross-reactive not only
with the FSH of other mammals but also with that
of birds, turtles, crocodiles and amphibians. Usually only one GTH is present in fish and this
shows species-specific differences in structure and
activity. For example, androgen production in
mammalian testis is stimulated to the same extent
by the GTH from Tilapia sp. as by mammalian
LH, but is stimulated 500-fold less by the GTH
from Muraenesox cinereus. The salmonids contain two gonadotropins, GTH-I and GTH-II,
which are produced in different cells of the hypophysis and differ greatly in their ~ subunits. The
subunit GTH-I~ has only 31 % sequence agreement with GTH-II~, but almost 40 % agreement
with human LH~ and FSH~. In contrast, GTHII~ is very similar to the ~ subunits of other teleost GTHs and has higher sequence similarity to
human LH~ (48%) than to FSH~ (38%). Thus,
the differentiation between LH and FSH is
already indicated here [87]. The in vitro association of the a and ~ subunits of mammalian LH
proceeds very slowly, requiring several hours at
normal body temperature and several days at low
temperatures. Fish GTHs, in contrast, show
adaptation to low temperature, e.g. the association of GTH subunits of carp is almost complete
after 45 min at 20°C. Hybrids of bovine LHa and
Cyprinus gonadotropin j3 associate at an intermediate rate.
The choriongonadotropins have been examined in detail only in the primates and Equidae,
but have also been detected in the rat, mouse,
guinea-pig, rabbit and sheep. The human and
equine CG~ chains are 30 amino acids longer at
the C-terminus than are the 115-118 amino acids
of LH~ and FSH~; this implies a stop-codon
mutation and is probably related to the localization in the placenta [213]. There is only one
human LH~ gene but seven genes for CG~,
although only three are expressed. There is also
only one CGa gene, but despite this there is a surplus of a chains in the placenta [213]. In the
horse, the amino acid sequences of the ~ chains
from LH and CG are identical, including the Cterminal extension typical of CG; only the carbo8.3.1 Glycoproteins of the Adenohypophysis
295
hydrate contents are different, with 24 % in LH
compared with 45 % in CG. As a result of these
particular characters, equine LHlCG has both
LH and FSH activity; furthermore, the LHlCG ~
subunits can be combined only with a subunits of
the same species and, unlike other ~ subunits,
cannot form hybrid molecules [23, 213]. Peptides
that are immunologically similar to LH and FSH
have been detected in the CNS of the cockroach
Periplaneta americana; these substances stimulate
testosterone secretion in the Leydig cells of
mouse testis [223].
The gonads and the placenta produce two peptides which inhibit FSH release from the anterior
lobes of the hypophysis by a negative-feedback
mechanism; these are inhibin A and B. They are
heterodimers of a glycosylated a chain of 16 kDa
and a ~ chain of 14 kDa, which occurs in pigs and
cattle as two sequence variants [35, 210]. In addition to the inhibins, the follicle fluid also contains
homo- and heterodimers of the ~ subunits, which
stimulate FSH release and are consequently referred to as activins. Finally, this fluid also contains
a monomeric glycoprotein of 35 kDa, follistatin,
which is apparently not related to the inhibins but
nevertheless inhibits FSH release [201].
8.3.2 Pro-Opiomelanocortins
Adrenocorticotropin (ACTH), the Iipotropins (~and y-LPH), the melanotropins (a-, ~- and yMSH) and the opioid endorphins (~- and aEND) arise by proteolysis of a common precursor, pro-opiomelanocortin (PO Me) (Fig. 8.3).
The hormone-coding domains in this case are also
flanked by pairs of basic amino acids which are
attacked by specific serine proteases. After cleavage, the peptides are further modified, e.g. glycosylated (ACTH), N-acetylated (a-MSH, ~END), C-terminal amidated (a-MSH), Serf
Thr phosphorylated (CLIP), or Tyr sulphated
(ACTH). The processing is tissue specific: the
POMC produced in the pars distalis gives primarily ACTH and ~-LPH; in the pars intermedia,
ACTH is in part further cleaved to a-MSH and
CLIP, and ~-LPH to y-LPH and ~-END, and in
some species also to ~-MSH [185]. In Xenopus
laevis, and apparently also in the salmon Oncorhynchus keta and other vertebrates, there are two
POMC genes, and thus two sets of cleavage products [133,249]. The POMC mRNA of O. keta
lacks the coding sequence for y-MSH [101].
Human ACTH differs from that of the mouse
in 2, from that of the frog in 9 and from that of the
e.g. from 16 % in bovine LH to 45 % in equine
CG.
The amphibians, turtles, crocodiles, birds and
mammals produce two different gonadotropins
(GTH): FSH and LH. There is apparently only
one GTH present in lizards and snakes, and this is
immunologically distinct from mammalian FSH
but has no LH activity. On the other hand, sheep
FSH is immunologically cross-reactive not only
with the FSH of other mammals but also with that
of birds, turtles, crocodiles and amphibians. Usually only one GTH is present in fish and this
shows species-specific differences in structure and
activity. For example, androgen production in
mammalian testis is stimulated to the same extent
by the GTH from Tilapia sp. as by mammalian
LH, but is stimulated 500-fold less by the GTH
from Muraenesox cinereus. The salmonids contain two gonadotropins, GTH-I and GTH-II,
which are produced in different cells of the hypophysis and differ greatly in their ~ subunits. The
subunit GTH-I~ has only 31 % sequence agreement with GTH-II~, but almost 40 % agreement
with human LH~ and FSH~. In contrast, GTHII~ is very similar to the ~ subunits of other teleost GTHs and has higher sequence similarity to
human LH~ (48%) than to FSH~ (38%). Thus,
the differentiation between LH and FSH is
already indicated here [87]. The in vitro association of the a and ~ subunits of mammalian LH
proceeds very slowly, requiring several hours at
normal body temperature and several days at low
temperatures. Fish GTHs, in contrast, show
adaptation to low temperature, e.g. the association of GTH subunits of carp is almost complete
after 45 min at 20°C. Hybrids of bovine LHa and
Cyprinus gonadotropin j3 associate at an intermediate rate.
The choriongonadotropins have been examined in detail only in the primates and Equidae,
but have also been detected in the rat, mouse,
guinea-pig, rabbit and sheep. The human and
equine CG~ chains are 30 amino acids longer at
the C-terminus than are the 115-118 amino acids
of LH~ and FSH~; this implies a stop-codon
mutation and is probably related to the localization in the placenta [213]. There is only one
human LH~ gene but seven genes for CG~,
although only three are expressed. There is also
only one CGa gene, but despite this there is a surplus of a chains in the placenta [213]. In the
horse, the amino acid sequences of the ~ chains
from LH and CG are identical, including the Cterminal extension typical of CG; only the carbo8.3.1 Glycoproteins of the Adenohypophysis
295
hydrate contents are different, with 24 % in LH
compared with 45 % in CG. As a result of these
particular characters, equine LHlCG has both
LH and FSH activity; furthermore, the LHlCG ~
subunits can be combined only with a subunits of
the same species and, unlike other ~ subunits,
cannot form hybrid molecules [23, 213]. Peptides
that are immunologically similar to LH and FSH
have been detected in the CNS of the cockroach
Periplaneta americana; these substances stimulate
testosterone secretion in the Leydig cells of
mouse testis [223].
The gonads and the placenta produce two peptides which inhibit FSH release from the anterior
lobes of the hypophysis by a negative-feedback
mechanism; these are inhibin A and B. They are
heterodimers of a glycosylated a chain of 16 kDa
and a ~ chain of 14 kDa, which occurs in pigs and
cattle as two sequence variants [35, 210]. In addition to the inhibins, the follicle fluid also contains
homo- and heterodimers of the ~ subunits, which
stimulate FSH release and are consequently referred to as activins. Finally, this fluid also contains
a monomeric glycoprotein of 35 kDa, follistatin,
which is apparently not related to the inhibins but
nevertheless inhibits FSH release [201].
8.3.2 Pro-Opiomelanocortins
Adrenocorticotropin (ACTH), the Iipotropins (~and y-LPH), the melanotropins (a-, ~- and yMSH) and the opioid endorphins (~- and aEND) arise by proteolysis of a common precursor, pro-opiomelanocortin (PO Me) (Fig. 8.3).
The hormone-coding domains in this case are also
flanked by pairs of basic amino acids which are
attacked by specific serine proteases. After cleavage, the peptides are further modified, e.g. glycosylated (ACTH), N-acetylated (a-MSH, ~END), C-terminal amidated (a-MSH), Serf
Thr phosphorylated (CLIP), or Tyr sulphated
(ACTH). The processing is tissue specific: the
POMC produced in the pars distalis gives primarily ACTH and ~-LPH; in the pars intermedia,
ACTH is in part further cleaved to a-MSH and
CLIP, and ~-LPH to y-LPH and ~-END, and in
some species also to ~-MSH [185]. In Xenopus
laevis, and apparently also in the salmon Oncorhynchus keta and other vertebrates, there are two
POMC genes, and thus two sets of cleavage products [133,249]. The POMC mRNA of O. keta
lacks the coding sequence for y-MSH [101].
Human ACTH differs from that of the mouse
in 2, from that of the frog in 9 and from that of the