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

SON, PVN
(AVP, OXY)
Hypothalamus
AVP,
OXY
Posterior
lobe
Kidney, uterus,
mammary gland
Portal
system
Anterior
lobe
PVN
(TRH, CRH, SST)
ARC
(GHRH, GnRH,
DA)
Releasing
factors
Trophic hormones
(ACTH, TSH, GH,
LH, FSH, prolactin)
Figure 38–1. Organization of the anterior and posterior pituitary
gland. Hypothalamic neurons in the supraoptic (SON) and paraventricular
(PVN) nuclei synthesize arginine vasopressin (AVP)
or oxytocin (OXY). Most of their axons project directly to the
posterior pituitary, from which AVP and OXY are secreted into
the systemic circulation to regulate their target tissues. Neurons
that regulate the anterior lobe cluster in the mediobasal hypothalamus,
including the PVH and the arcuate (ARC) nuclei. They
secrete hypothalamic releasing hormones, which reach the anterior
pituitary via the hypothalamic-adenohypophyseal portal system
and stimulate distinct populations of pituitary cells. These
cells, in turn, secrete the trophic (signal) hormones, which regulate
endocrine organs and other tissues. See Table 38-1 for
abbreviations.
Hormone excess similarly can result either from
primary disorders at the level of the target endocrine
glands (e.g., a hyperfunctioning tumor of the adrenal cortex
that oversecretes cortisol) or from secondary disorders
at the level of the pituitary gland (e.g., a pituitary
corticotrope adenoma that oversecretes corticotropin, the
predominant stimulator of adrenal glucocorticoid biosynthesis).
Again, knowledge of the levels of the pituitary
signal hormone and the target hormone allows the clinician
to identify the site of the endocrine disorder.
PITUITARY HORMONES AND THEIR
HYPOTHALAMIC RELEASING FACTORS
The peptide hormones of the anterior pituitary are essential
for the regulation of growth and development, reproduction,
response to stress, and intermediary
metabolism. Their synthesis and secretion are controlled
by hypothalamic hormones and by hormones from the
peripheral endocrine organs. A large number of disease
states, as well as a diverse group of drugs, also affect
their secretion. The complex interactions among the
hypothalamus, pituitary, and target endocrine glands
provide elegant examples of the integrated feedback regulation
described earlier. Clinically, an improved understanding
of the mechanisms that underlie these
interactions provides the rationale for diagnosing and
treating endocrine disorders and for predicting certain
side effects of drugs that affect the endocrine system.
Moreover, the elucidation of the structures of the anterior
pituitary hormones and hypothalamic releasing hormones
and advances in protein chemistry and molecular
biology have made it possible to produce synthetic peptide
agonists and antagonists that have important diagnostic
and therapeutic applications.
The anterior pituitary hormones can be classified
into three different groups based on their structural features
(Table 38–2). Corticotropin (adrenocorticotrophic
hormone, ACTH) and α-melanocyte-stimulating hormone
(α-MSH) are part of a family of peptides derived
from pro-opiomelanocortin (POMC) by proteolytic
processing (Chapters 18 and 42). Growth hormone
(GH) and prolactin belong to the somatotropic family
of hormones, which in humans also includes placental
lactogen. The glycoprotein hormones—thyroidstimulating
hormone (TSH; also called thyrotropin),
luteinizing hormone (LH; also called lutropin), and folliclestimulating
hormone (FSH; also called follitropin)—
share a common α-subunit but have different β-subunits
that determine their distinct biological activities. In
humans, the glycoprotein hormone family also includes
human chorionic gonadotropin (hCG).
The synthesis and release of anterior pituitary
hormones are influenced by the central nervous system
(CNS). Their secretion is positively regulated by a
group of peptides referred to as hypothalamic releasing
hormones, which are released from hypothalamic
neurons in the region of the median eminence and
reach the anterior pituitary through the hypothalamicadenohypophyseal
portal system (Figure 38–1). The
hypothalamic- releasing hormones include corticotropinreleasing
hormone (CRH), growth hormone–releasing
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CHAPTER 38
INTRODUCTION TO ENDOCRINOLOGY: THE HYPOTHALAMIC-PITUITARY AXIS