Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

II. Anterior Lobe and Intermediate Lobe
579
Pig/Dog FPAMPLSSLFANAVLRAQHLHQLAADTYKEFERAYIPEGQRYS IQNAQAAFCFSETIPAPTGKDE 65
Cat ------------------------------------------- ----------------------
Horse ------------------------------------------- ----------------------
Mouse ----------S-------------------------------- --------------------E-
Rat ------------------------------------------- --------------------E-
Goat ----S--G-------------------F-----T--------- ---T-V--------------N-
Sheep ----S--G-------------------F-----T--------- ---T-V--------------N-
Cattle ----S--G-------------------F-----T--------- ---T-V--------------N-
Human --TI---R--D--M---HR-----F---Q---E----KE-K--FLQ-P-TSL----S--T-SNRE-
** ** ** ** *** ***** ** *** *** * ** * * **** ** * *
Pig/Dog AQQRSDVELLRFSLLLIQSWLGPVQFLSRVFTNSLVFGTSD RVYEKLKDLEEGIQALMRELEDGS 130
Cat ----------------------------------------- ------------------------
Horse ------M------------------L--------------- ------R-----------------
Mouse ----T-M----------------------I-----M----- -----------------Q------
Rat ----T-M----------------------I-----M----- -----------------Q------
Goat ---K--L----I-----------L----------------- -------------L--------VT
Sheep ---K--L----I-----------L----------------- -------------L--------VT
Cattle ---K--L----I-----------L----------------- -------------L---------T
Human T--K-NL----I---------EP--------A----Y-A--SN--DL---------T--GR-----
** **** ********* * *** * *** * ** ** * ****** ** ***
Pig/Dog PRAGQILKQTYDKFDTNLRSDDALLKNYGLLSCFKKDLHKAETYLRVMKCRRFVESSCAF 190
Cat --G---------------------------------------------------------
Horse ------------------------------------------------------------
Mouse --V------------A-M------------------------------------------
Rat --I------------A-M-----------------------------------A------
Goat -----------------M----------------------T------------G-A----
Sheep ---------------R-M----------------R-----T------------G-A----
Cattle -----------------M----------------R-----T------------G-A----
Human --T---F----S-----SHN-----------Y--R--MDKV--F--IVQ--S --G--G-
** *** **** *** *********** ** ** ** ** ** * ** *
FIGURE 18-11 Sequence comparison of GH. See the legend for Figure 18-6 .
Pig
Dog
Cat
Horse
Mouse
Rat
Goat
Sheep
Cattle
Human
in the mammary gland as it is demonstrated also in cats with
progestin-induced fibroadenomatous changes of the mammary
gland ( Mol et al. , 1995b ), and GH mRNA has been
demonstrated in the normal and neoplastic human mammary
gland as well ( Mol et al. , 1995a ; Mol et al. , 1996 ). The presence
of a putative binding site for the progesterone receptor
in the GH promoter of human, rat, mouse, and dog makes it
likely that progestin-induced GH expression is a direct effect
of activated PRs on the GH gene promoter ( Lantinga-van
Leeuwen et al. , 2002 ) .
Apart from the mammary gland, extrapituitary GH
expression seems to be widespread throughout the body.
GH functions already as an early local embryonic growth,
and differentiation factor, including the neural tube, before
pituitary GH expression is detectable ( Sanders and Harvey,
2004 ). Furthermore, GH expression is found in the postnatal
rat lung ( Beyea et al. , 2005 ), chicken testis ( Harvey et al. ,
2004 ) and canine lymphomas ( Lantinga van Leeuwen et al. ,
2000 ), insulinomas ( Robben et al. , 2002 ), and growth plate
or osteosarcomas ( Kirpensteijn et al. , 2002 ).
c . (Pro)hormone
GH is a single-chain polypeptide. It contains two intrachain
disulfide bridges and has an apparent molecular weight of
22,000. In humans, a small fraction of circulating GH has a
molecular weight of 20 kDa because of alternative splicing
of the pituitary GH gene. The metabolic effects are comparable
to the normal 22 kDa form ( Hayakawa et al. , 2004 ).
The amino acid sequence of GH belongs to the best-known
sequences of pituitary hormones among species ( Fig. 18-11 ).
The sequences of canine and porcine GH are identical and
very similar to the horse. The canine and porcine sequence is
suggested to be identical to the GH sequence for the ancestral
placental mammal ( Forsyth and Wallis, 2002 ).
In cattle, a polymorphism in the GH gene exists, resulting
in four GH variants that can arise from two possible
N-terminal amino acids (phenylalanine or alanine) and two
amino acids in position 127 (leucine or valine). The transmission
of the trait of high milk production was greater for
homozygous leucine-127 in Holstein cows and valine-127
in Jersey cows ( Lucy et al. , 1993 ). GH exhibits also heterogeneity
because of posttranscriptional processing
that may vary in binding to the plasma GH binding protein
(GHBP) or biological effects ( De Palo et al. , 2006 ).
The glycine in the third α -helix of bovine GH (G118) and
human GH (G120) is crucial for biological functioning of
GH. Substitution of this glycine results in a molecule without
growth-promoting activity that inhibits the actions of
GH in vitro and in vivo ( Kopchick, 2003 ).
d . Secretion
The release of GH by the pituitary is regulated by a variety
of factors ( Fig. 18-12 and Table 18-5 ). The integration of
all these factors results in a pulsatile release of GH. In the
female dog, plasma GH pulse patterns are dependent on the
estrus cycle. In the early luteal phase, elevated basal GH
concentrations are associated with a low pulse frequency
of 2 peaks/12 h, whereas at anestrus lower basal GH concentrations
are found with an enhanced pulse frequency of