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

II. Anterior Lobe and Intermediate Lobe
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1986 ; Rijnberk et al. , 1987 ) caused significant increases
in circulating α -MSH. More detailed information pertaining
to some of these tests is presented in Section IV and in
Table 18-4 .
2 . β -Endorphin/ β -Lipotropin
a . Gene Expression and Biosynthesis
Both β -lipotropin and β -endorphin are derived from the
precursor protein POMC. The gene expression of POMC
has been described in Section II.A.1. β -Lipotropin ( β -
LPH) consists of the 91 C-terminal amino acids of the
POMC precursor. It is synthesized in the corticotropic cells
of both the AL and IL. The C-terminal sequence (36-91)
is remarkably similar in human, porcine, and ovine pituitaries,
whereas the N-terminal sequence (1-36) is rather
heterogeneous. β -MSH (sequence 37-58) appears to be an
extraction artifact and plays no physiological role.
By proteolytic cleavage at amino acid 61, γ-LPH
( β -LPH[1-61]) and a family of endorphins are formed.
Through specific deletion of C-terminal amino acids and
N-terminal acetylation, a variety of β-END-related peptides
are formed. The three main compounds are β-END(61-91),
γ -END(61-77), and α -END(61-76). The corticotropic cells
of the AL synthesize approximately equal or higher concentrations
of β -LPH than of β -END(1-31) in most species.
The equine AL, however, contains primarily β-END(1-31)
and N-acetyl- β -END(1-27) ( Millington et al. , 1992 ).
The corticotropic/melanotropic cells of the IL produce
relatively more β -END and related peptides. In the IL of
the normal dog, the ratio β -LPH/ β -END is less than 0.1
( Krieger, 1983 ). In the dog, β -END(1-27) is the most abundant
form in the IL ( Young and Kemppainen, 1994 ).
b . Secretion
The stimuli that induce ACTH or α -MSH release from
either the AL or IL cells cause also a release of the β -LPHrelated
peptides from the same cell. The cellular subset of
specific proteolytic, amidating, and acetylating enzymes
present in the secretory vesicles defines the ultimate composition
of POMC-derived peptides that are secreted into
the blood. The secretion of the IL is mainly under control
of multiple neurotransmitters ( Saland, 2001 ). In fearful
dogs, only marginal increases in plasma β -END were measured
after a gunshot test ( Hydbring-Sandberg et al. , 2004 ).
In horses, a critical exercise threshold exists before plasma
β -END concentrations increase ( Mehl et al. , 2000 ).
c . Action
The main action of β -LPH is to mobilize fat from adipose
tissues, as demonstrated in the rabbit. Its biological function
in humans and other species has not been fully elucidated.
Brain tissue can break down β -LPH to form β-END-related
peptides. However, it is questionable whether these pituitary
peptides are involved in brain function; in conscious sheep,
hemorrhagic stress elevates β -END concentrations in plasma
but not in cerebrospinal fluid ( Smith et al. , 1986 ).
β -END is an endogenous opiate with a potent morphinomimetic
action. It is also produced in the hypothalamus
where the entire POMC precursor is present. Brain and
pituitary endorphin are probably part of separate systems.
The role of β -END and other opioid peptides in the secretion
of pituitary hormones has been studied with long-acting
analogues, opiates, and opioid receptor antagonists
( Estienne and Barb, 2005 ; Molina, 2006 ).
d . Disease/Tests
Hypersecretion of β -END is associated with the ACTH
hypersecretion of IL tumors in both equine and canine
pituitary-dependent hyperadrenocorticism ( Orth et al. ,
1982 ; Peterson et al. , 1986 ; Rijnberk et al. , 1987 ). As the
regulation of the secretion of β -END is similar to that of
other POMC-derived peptides from the AL and IL, testing
procedures can be applied as mentioned in the section on
ACTH and α -MSH. Elevation of plasma β -END has been
documented in horses following running and shipping
( Li and Chen, 1987 ) and in sheep during electroimmobilization
and shearing procedures ( Jephcott et al. , 1987 ).
Treadmill exercise of Thoroughbred horses induces a variable
response in plasma β -END concentrations ( Art et al. ,
1994 ). Elevated plasma β -END concentrations are found
in dogs with congestive heart failure ( Himura et al. , 1994 )
and are further elevated after naloxone treatment.
B . Glycoprotein Hormones
The gonadotropes and thyrotropes synthesize the hormones
LH, FSH, and TSH, each of which consists of two different
peptide chains, termed the α - and β -subunits. The amino
acid sequence of the α -subunit is identical for LH, FSH,
and TSH within a species, as it is for placental chorionic
gonadotropin. The β -subunits have unique structures and
determine the hormone specificity. Carbohydrate substituents
account for 10% to 20% of the molecular weights of
these hormones.
1 . α -Subunit
a . Gene Expression
The gene encoding the α -glycoprotein subunit ( α GSU) varies
between 8 and 16.5 kb among the species and contains
four exons. The α -subunit comes to expression in a variety
of cells such as thyrotropes, gonadotropes, and syncytiotrophoblasts.
The expression in gonadotropes and thyrotropes
is in part differently regulated. In the developing pituitary
α GSU is one of the first hormones to be detected and
regulated by the transcription factors Pitx1, Lhx3, SF-1,
Otx1 ( Brown and McNeilly, 1999 ; Cohen and Radovick,