chapter 30
Endocrine Metabolism I: Introduction
FIGURE 30-11
Mechanism of prolactin receptor activation. Activation of prolactin receptor consists of ligand-induced sequential
receptor homodimerization driven by the two binding sites of prolactin. In the intracellular domain of the homodimer of
the ligand-receptor complex, a tyrosine kinase [known as Janus kinase 2 (Jak-2)] is activated. Jak-2 kinase causes
autophosphorylation and phosphorylation of the receptor. [Reproduced with permission from M. E. Freeman,
B. Kanyicska, A. Lerant, and G. Nagy,
Physiological R eviews
80, 1530 (2000).]
that are
to glucose
The IGF-I receptor is an
heterotetramer that is
structurally similar to the insulin receptor but is coded
for by a different, single-copy gene located within bands
q25-26 of chromosome 15. Like the insulin receptor, with
which it shares 50-60% sequence homology, the IGF-I
receptor has a cysteine-rich domain in the
for ligand binding and a tyrosine kinase domain in the
subunit that catalyzes transphosphorylation of contralat-
eral /3-subunit sites. The receptor has highest affinity for
IGF-I, a lesser affinity for IGF-II (about 2- to 15-fold less),
and low affinity for insulin (about ~
1 0 0
- to
1 0 0 0
less) due to the absence of insulin-binding determinants
in the
Receptors for Growth Hormone and Prolactin
Growth hormone (GH) and prolactin (PRL) belong to
the “helix bundle peptide” (HBP) hormone family, which
includes human placental lactogen (hPL), erythropoietin
(EPO), and many interleukins and cytokines. All members
of this family have similar mechanisms of action; they
utilize membrane receptors that are straight-chain glyco-
proteins with extracellular, transmembrane and intracel-
lular domains. The membrane receptors for this group of
hormones when bound with their respective receptors un-
dergo dimerization. Each dimerized receptor is bound to
one molecule of hormone. The intracellular events of the
ligand-mediated activation of the receptor consists of acti-
vation of a constitutively associated tyrosine kinase known
as Janus kinase 2 (Jak-2). Jak-2 kinase transphosphory-
lates itself and phosphorylâtes the intracellular domains
of the receptor. Figure 30-11 illustrates the mechanism
of prolactin receptor activation. The signal transduction
pathways for GH and PRL are discussed in Chapter 31.
30.6 Organization of the Endocrine System
The nervous and endocrine systems function in a coordi-
nated manner to promote growth, homeostasis, and repro-
ductive competence. The need to rapidly adjust physio-
logical processes in response to impending disturbances
in homeostasis is met by the nervous system, while the
endocrine system effects the more prolonged, fine-tuned
adjustments. Together, they effect appropriate organismic
adaptation. Some interdependence also exists between the
two systems. The nervous system, for example, relies
heavily on a continuous supply of glucose, the circulat-
ing levels of which are under multiple hormonal control,
while maturation of the nervous system is regulated by thy-
roid hormone, and maintenance of mental acuity in adults
depends on the availability of both thyroid hormone and
glucocorticoids. On the other hand, hormone production is
generally dependent on the nervous system, albeit to vary-
ing extents. The synthesis of insulin, glucagon, calcitonin,
parathyroid hormone, and aldosterone appears to require
little or no neural regulation, whereas that of the hypotha-
lamic peptides and adrenal medullary hormones is totally
dependent on it. It may be significant that those hormones
which are relatively independent of neural control serve
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