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P A R T 6
Drugs acting on the endocrine system
THE HYPOTHALAMUS
The
hypothalamus
is the coordinating centre for
the nervous and endocrine responses to internal
and external stimuli. The hypothalamus constantly
monitors the body’s homeostasis by analysing input
from the periphery and the central nervous system
(CNS) and coordinating responses through the auto
nomic, endocrine and nervous systems. In effect, it is
the “master gland” of the neuroendocrine system. This
title was once given to the pituitary gland because of
its many functions and well-protected location (see later
discussion).
The hypothalamus has various neurocentres—areas
specifically sensitive to certain stimuli—that regulate a
number of body functions, including body temperature,
thirst, hunger, water retention, blood pressure, respir
ation, reproduction and emotional reactions. Situated
at the base of the forebrain, the hypothalamus receives
input from virtually all other areas of the brain, includ
ing the limbic system and the cerebral cortex. Because
of its positioning, the hypothalamus is able to influence,
and be influenced by, emotions and thoughts. The hypo
thalamus is also located in an area of the brain that is
poorly protected by the blood–brain barrier, so it is able
to act as a sensor to various electrolytes, chemicals and
hormones that are in circulation and do not affect other
areas of the brain.
The hypothalamus maintains internal homeostasis
by sensing blood chemistries and by stimulating or sup
pressing endocrine, autonomic and CNS activity. In
essence, it can turn the autonomic nervous system and
its effects on or off. The hypothalamus also produces
and secretes a number of
releasing hormones or factors
that stimulate the pituitary gland, which in turn stimu
lates or inhibits various endocrine glands throughout
the body (see Figure 34.1). These releasing hormones
include growth hormone–releasing hormone (GHRH),
thyrotropin-releasing hormone (TRH), gonadotropin-
releasing hormone (GnRH), corticotropin-releasing
hormone (CRH) and prolactin-releasing hormone
(PRH). The hypothalamus also produces two inhibiting
factors that act as regulators to shut off the produc
tion of hormones when levels become too high: growth
hormone release–inhibiting factor (somatostatin) and
prolactin-inhibiting factor (PIF). Recent research has
indicated that PIF may actually be dopamine, a neuro
transmitter. People who are taking dopamine-blocking
drugs often develop galactorrhoea (inappropriate milk
production) and breast enlargement, theoretically
because PIF is also blocked and prolactin levels continue
to rise, stimulating breast tissue and milk production.
Research is ongoing about the chemical structure of
several of the releasing factors.
The hypothalamus is connected to the pituitary
gland by two networks: A vascular network carries the
hypothalamic releasing factors directly into the anterior
pituitary, and a neurological network delivers two other
hypothalamic hormones—antidiuretic hormone (ADH)
and oxytocin—to the posterior pituitary to be stored.
These hormones are released as needed by the body
when stimulated by the hypothalamus.
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TABLE 34.1 Endocrine glands with associated hormones and clinical effects
Gland
Hormones produced
Principal effects
Adrenal cortex
Cortisol
Increases glucose levels, suppresses inflammatory and immune
reactions
Intestine
Aldosterone
Sodium retention, potassium excretion
Secretin,
cholecystokinin
Decreases gastric movement, stimulates bile and pancreatic juice
secretion
Kidney (juxtaglomerular
cells)
Erythropoietin
Increases red blood cell production
Renin
Stimulates increase in blood pressure and vascular volume
Ovaries
Oestrogen,
progesterone
Promotes secondary sex characteristics, prepares the female
body for pregnancy
Pancreas
Insulin, glucagon,
somatostatin
Regulation of glucose, fat metabolism (islets of Langerhans)
Parathyroid glands
Parathyroid hormone
Increases serum calcium levels
Pineal gland
Melatonin
Affects secretion of hypothalamic hormones, particularly
gonadotropin-releasing hormone
Placenta
Oestrogens,
progesterones
Maintains fetal growth and development, prepares the body for
birth
Stomach
Gastrin
Stimulates stomach acid production
Testes
Testosterone
Stimulates secondary sex characteristics in males
Thyroid
Thyroid hormone
Stimulates basal metabolic rate (how the body uses energy)
Calcitonin
Decreases serum calcium levels
