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

578
Chapter | 18 Pituitary Function
progesterone secretion. The LH effects are mediated by
LHR containing granulosa cells through the release of
EGF-like growth factors ( Conti et al. , 2006 ).
FSH is essential for Sertoli cell proliferation and maintenance
of sperm quality in the male testis. LH interacts
predominantly with Leydig cells and stimulates the production
of testosterone.
e . Disease/Tests
LH and the LHR are also involved in the pathogenesis of
adrenal tumors in ferrets, which develop after castrationinduced
high plasma LH concentrations ( Schoemaker et
al. , 2002b ). In the adrenal carcinomas that secrete predominantly
adrenal androgens, the presence of LHR mRNA
and protein has been demonstrated.
The LHR is expressed constitutively in urogenital tissues
and adrenal glands in rodents, but they need functional
maturation at a posttranslational level ( Apaja et al. , 2005 ).
Dogs have also LHR and FSHR in the lower urinary tract
( Ponglowhapan et al. , 2006 ). In long-term spayed bitches,
relative lower plasma LH and FSH concentrations were
found in dogs with urinary incontinence in comparison
with continent dogs ( Reichler et al. , 2005 ).
C . Somatomammotropic Hormones
Growth hormone (GH) and prolactin (PRL) together with
the placental lactogen show homology in amino acid composition
and some biological activities. Therefore, they may
group together as a family of somatolactotropic hormones.
There is increasing evidence that these hormones evolved
from a single ancestral gene (Seo, 1985; Wallis, 1984) .
1 . GH
The somatotropic cells, producing GH, are the most abundant
cells of the anterior lobe.
a . Gene Expression
In primates, multiplication of the GH gene has resulted
in a cluster of five GH-related genes. The GH-N gene is
expressed in the pituitary and the other four, consisting of
the chorionic somatomammotropins (so-called placental lactogens)
and a variant gene (GH-V), are expressed in the placenta
during pregnancy. In most nonprimates, a single gene
encodes GH, but a family of PRL-like genes (also including
placental lactogens) is present. In sheep and goats in
some individuals, there are two GH-like genes from which
one may be expressed in the placenta. In red deer, two gene
sequences encoding GH were found, but this is shown to be
related to allelic polymorphism ( Wallis et al. , 2006 ).
The GH-producing cells arise from a lineage of TSH-, GH-,
and PRL-producing pituitary cells by the action of transcription
factor Pit-1 that is under the control of the prophet of Pit-1
(Prop1). The final maturation of GH-producing cells is under
the control of transcription factors Pitx1, Zn-15, Lhx3, and
Pit1 ( Mullis, 2005 ). Pit1 and GH expression are already found
at the 8- to 16-cell stage in bovine embryos ( Joudrey et al. ,
2003 ). For the activation of the pituitary GH gene, a 5 -remote
locus control region in humans 14.5 kb upstream of the GH-N
promoter plays an important role ( Ho et al. , 2006 ). This site
contains also three Pit1 binding sites ( Shewchuk et al. , 2002 ).
The pituitary somatotroph differentiation is further stimulated
by glucocorticoids and thyroid hormone ( Porter, 2005 ).
GH mRNA expression is stimulated by GHRH and ghrelin
by inducing cAMP production and subsequently Pit1
mRNA expression ( Garcia et al. , 2001 ; Theill and Karin,
g993 ; Yan et al. , 2004 ). Somatostatin (SS) inhibits in general
GH release although in porcine somatotropes SS can also
stimulate GH release depending on the dose used. It appeared
that SS receptors SST1 and SST2 mediate the inhibitory
effects whereas SST5 mediates a stimulatory effect of somatostatin
( Luque et al. , 2006 ). The rat GH promoter contains a
positive thyroid hormone response element (TRE) and a negative
TRE (nTRE) ( Sanchez-Pacheco and Aranda, 2003 ). GH
expression is stimulated by the positive TRE. In the absence
of T 3 binding the unliganded thyroid hormone receptor (TR)
may induce GH expression in nonpituitary cells. In severely
hypothyroid dogs elevated plasma GH concentrations have
been found, which may be related to this mechanism ( Lee
et al. , 2001 ). Gonadal steroids modulate also GH production.
17 β -Estradiol may reduce the inhibitory effect of SS on
GH production, whereas testosterone treatment increases GH
mRNA concentrations in adulthood ( Chowen et al. , 2004 ).
b . Extrapituitary GH Expression
In dogs, endogenous progesterone and exogenous progestins
may induce considerable rises in plasma GH
concentrations, resulting in acromegalic changes and insulin
resistance with the possibility of development of frank
diabetes mellitus ( Eigenmann et al. , 1983a ; Selman et al. ,
1994a ). GH excess has only been found to occur in intact
female dogs during the progesterone-dominated phase of the
sexual cycle or in dogs treated with progestins ( Eigenmann
and Rijnberk, 1981 ).
Selman et al. , showed the autonomous character of
progestin-induced GH secretion ( Selman et al. , 1991 ) and
found the canine mammary gland to be the source of plasma
GH after progestin treatment ( Selman et al. , 1994b ). The
mammary origin was confirmed by an arterial-venous gradient
across the mammary gland, a rapid decrease and normalization
of plasma GH concentrations after complete
mammectomy ( Selman et al. , 1994b ), and the presence of
GH mRNA in the canine mammary gland as measured by
RT-PCR ( Mol et al. , 1995b ). From the 100% sequence identity
it is concluded that a single gene encodes pituitary and
mammary GH in the dog, in agreement with the fact that
only one canine GH gene is found in the published canine
genome sequence. The dog is not unique in expressing GH