DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Introduction To Endocrinology:
The Hypothalamic-Pituitary Axis
Keith L. Parker
and Bernard P. Schimmer
ENDOCRINOLOGY AND HORMONES:
GENERAL CONCEPTS
Endocrinology analyzes the biosynthesis of hormones,
their sites of production, and the sites and mechanisms
of their action and interaction. The term hormone is of
Greek origin and classically refers to chemical messengers
that circulate in body fluids and produce specific
effects on cells distant from their point of origin. The
major functions of hormones include the regulation of
energy storage, production, and utilization; the adaptation
to new environments or conditions of stress; the
facilitation of growth and development; and the maturation
and function of the reproductive system. Although
hormones were originally defined as products of ductless
glands, we now appreciate that many organs that
were not classically considered as “endocrine” (e.g., the
heart, kidneys, GI tract, adipocytes, and brain) synthesize
and secrete hormones that play key physiological
roles; many of these hormones are now employed either
diagnostically or therapeutically in clinical medicine. In
addition, the field of endocrinology has expanded to
include the actions of growth factors acting by means of
autocrine and paracrine mechanisms, the influence of
neurons—particularly those in the hypothalamus—that
regulate endocrine function, and the reciprocal interactions
of cytokines and other components of the immune
system with the endocrine system.
As discussed in Chapter 3, hormones generally
exert their actions on target cells via a plenitude of
receptors, including heptaspanning GPCRs, monospanning
membrane tyrosine kinases and guanylyl cyclases,
cytokine receptors, ligand-activated ion channels, and
nuclear transcription factors. Conceptually, it is useful to
divide hormones into two classes: those that act predominantly
via nuclear receptors to modulate transcription
in target cells and those that typically act via
membrane receptors to exert rapid effects on signal
transduction pathways. Steroid hormones, thyroid hormone,
and vitamin D belong to the first class, whereas
peptide and amino acid hormones are generally
assigned to the second class. The receptors for both
classes of hormones provide tractable targets for a
diverse group of compounds that are among the most
widely used drugs in clinical medicine.
DISORDERS OF ENDOCRINE
REGULATION
Because of their potent effects, circulating levels of hormones
generally are tightly regulated within a normal
range. The physiological strategies used to maintain the
appropriate levels of hormones range from relatively
simple ones involving direct feedback or feed-forward
mechanisms (e.g., the secretion of parathyroid hormone
by the parathyroid glands is inversely related to
the serum Ca 2+ concentration, which is sensed by a
GPCR termed the Ca 2+ -sensing receptor; Chapter 44)
to more complex ones involving reciprocal interactions
among the hypothalamus, anterior pituitary, and
endocrine glands (see the section “The Hypothalamic-
Pituitary-Endocrine Axis”).
Regardless of the mechanism, normal regulation
can be perturbed in disease states when a given hormone
is either over or underproduced or when its signaling
mechanisms are impaired. Understanding the normal
regulation and actions of the various hormones is critical
to both diagnosis and treatment of these endocrine