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chapter31
Endocrine Metabolism
II:
Hypothalamus and Pituitary
F I G U R E 3 1 - 3
Structure o f hum an growth horm one. [Reproduced with perm ission from R. K. M urray. D. K. G ranner, P. A. M ayes, and
V. W. R odw ell,
H a rp e r ’s B io ch em istry,
21st ed. (Norwalk: Appleton & Lange, 1988). © 1988 Appleton & Lange.]
in humans, and vice versa). GH from nonprimate species
does not promote growth in monkeys and humans; how-
ever, human GH promotes growth in subprimate species.
P la c e n ta l L a c to g e n
H
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V c
T rp 8 5
G ro w th H o rm o n e
n
- r
r
a
-
W /À
V
T rp
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P ro lac tin
i
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F I G U R E 3 1 - 4
Structural hom ology in the som atom am m otropin family. D iagram of basic
structure o f hum an chorionic som atom am m otropin, hum an growth
horm one, and ovine prolactin. Bars represent the peptide chains w ith the
am ino term inus at left and the carboxyl term inus at right. Shaded portions
o f each bar represent the areas of homology. Lines above the bars represent
disulfide bridges. [Reproduced w ith perm ission from H. D. Niall,
M. L. H ogan, et al.: Sequence o f the pituitary and placental lactogenic and
grow th horm ones: evolution from a prim ordial peptide by gene
reduplication.
P roc. N a tl. A ca d . Sci. U .S.A.
68,
866 (1971).]
Actions of GH
The actions of GH are initiated by its binding to the mem-
brane receptor of target cells. The GH and PRL recep-
tors are single-membrane-bound proteins that belong to
class I of the cytokine receptor superfamily (Chapter 30).
Each of the receptor contains an extracellular, transmem-
brane, and intracellular domain. Receptor activation be-
gins when one molecule of growth hormone (with its two
binding sites) binds to the first receptor, followed by bind-
ing to the second receptor resulting in receptor dimeriza-
tion. The hormone-receptor complex activates a tyrosine
kinase known as Janus kinase 2 (Jak-2) that is associated
with the proximal region of the intracellular domains of the
dimerized receptor (see Figure 30-11). Two Jak-2 kinases
transphosphorylate each other and also phosphorylate ty-
rosine residues of the receptor. Subsequent downstream
single transduction pathways are complex and may involve
activation of transcription proteins, mitogen-activated pro-
tein (MAP) kinase cascade, protein kinase C activation,
and phosphatidylinositol and Ca2+ pathway activation.
GH promotes transport and incorporation of amino
acids in skeletal muscle, cardiac muscle, adipose tissue,
