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

I. Hypothalamus-Pituitary System
563
Man
Cow
Horse
Pig
FIGURE 18-2 Schematic illustration
of median sections through mammalian
and avian pituitaries. Key ,
anterior lobe; , intermediate lobe;
, neural lobe. Redrawn from Batten
and Ingleton (1987).
Goat Dog Cat Bird
circulatory flow within the pituitary, that is, from the AL to
the NL, from there to the infundibulum, and then back to the
AL. The primary capillary plexus of the NL appears to be
well positioned in the minicirculatory system, controlling all
of the afferent vascular events and many of the efferent vascular
events in the pituitary ( Page, 1986 ).
The vascularization of the intermediate lobe is closely
linked to that of the neurohypophyis. In spite of the rich
blood supply of the NL, the IL is a poorly vascularized
structure. In horses the IL is supplied by a vast capillary or
sinusoidal plexus, which connects that in the AL with that
in the NL ( Okada et al. 1997 ).
4 . Pituitary Organogenesis and Ontogenesis
During embryogenesis the adenohypophysis develops from
Rathke’s pouch, which arises from the primitive roof of
the mouth in contact with the base of the brain. Rathke’s
pouch subsequently separates by constriction from the oral
cavity. The anterior wall thickens and forms the anterior
lobe of the adenohypophysis. This largest portion of the
adenohypophysis remains separated from the intermediate
lobe by the hypophyseal cleft, which is the residual lumen
of Rathke’s pouch. In several species ( Fig. 18-2 ), the adenohypophysis
also extends into a pars tuberalis that forms
a cuff or collar around the proximal neurohypophysis and
may even envelop part of the median eminence ( Batten and
Ingleton, 1987 ; Hullinger, 1993 ).
In the embryonic development, the anterior lobe undergoes
major cellular proliferation and differentiation ( Dubois
et al. 1997 ). Totipotent pituitary stem cells give rise to two
main cell lineages, the acidophilic (mammasomatotropic,
somatotropic, lactotropic) and the basophilic (corticotropic,
thyrotropic, and gonadotropic) differentiated pituitary cell
types. Determination of AL cell-type lineages results from
a temporally regulated cascade of homeodomain transcription
factors that are being dissected by genetic and molecular
approaches at a rapid pace ( Treier et al. 1998 ). Although most
pituitary developmental information has been acquired from
murine models, histological and pathogenetic observations
in others mammals and human subjects have corroborated
these developmental mechanisms. The transcription factor
Rpx (Rathke’s pouch homeobox) is the earliest known
specific marker for the adenohypophyseal primordium.
Rathke’s pouch expresses several transcription factors of the
LIM homeodomain family, including Lhx3 and Lhx4 ( Sheng
et al. 1997 ). Lhx3 is one of the earliest markers for cells
that are destined to form the AL and the IL and is required
for Pit-1 expression ( Sheng et al. 1996 ). The homeodomain
transcription factor Ptx1 behaves as a universal pituitary
regulator and activates transcription of α -GSU (the
α -subunit of gonadotroph hormones) and POMC ( Drouin
et al. 1998 ; Lamonerie et al. , 1996 ). Transcription factors
Tpit (T box transcription factor) ( Lamolet et al. , 2001 ) and
NeuroD1 ( Lamolet et al. , 2004 ) appear to be a prerequisite
for POMC expression and determine the development of
the corticomelanotrope cell lineage. TSH and gonadotropin
(LH and FSH)-expressing cells share the common
α -GSU expression under developmental control of GATA-
2. Prop-1, the prophet of Pit-1, stimulates the Pit-1 gene.
Pit-1 (or POU1F1), a POU -homeodomain transcription
factor, determines the development and appropriate temporal
and spatial expression of cells committed to GH,
PRL, and TSH. Corticotroph cell commitment, although
occurring earliest during fetal development, is independent
of Pit-1-determined cell lineages. Mutations arising
within these transcription factors may result in isolated or
combined pituitary hormone failure syndromes. German
shepherd dogs with pituitary dwarfism have a combined
deficiency of GH, TSH, and PRL together with impaired
release of gonadotropins, whereas ACTH secretion is intact
( Kooistra et al. , 2000c ). The transcription factors Lhx4
( van Oost et al. , 2002 ), Prop-1 ( Lantinga-van Leeuwen
et al. , 2000a ), Pit-1 ( Lantinga-van Leeuwen et al. , 2000b ),
and the LIF receptor gene ( Hanson et al. , 2006b ) have been
excluded as candidates for pituitary dwarfism in German
shepherds and the cause remains to be elucidated.
The posterior wall of Rathke’s pouch is closely apposed
to the neural tissue of the NL, thereby forming the intermediate
lobe (IL), which is well developed in most mammals,