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P A R T 6
Drugs acting on the endocrine system
the brain led early scientists to believe that it must be the
chief control gland. However, as knowledge of the endo
crine system has grown, scientists now designate the
hypothalamus as the master gland because it has even
greater direct regulatory effects over the neuroendocrine
system, including stimulation of the pituitary gland to
produce its hormones.
The anterior pituitary
The
anterior pituitary
produces six major hormones:
growth hormone (GH), adrenocorticotropic hormone
(ACTH), follicle-stimulating hormone (FSH), luteinising
hormone (LH), prolactin (PRL) and thyroid-stimulating
hormone (TSH, also called thyrotropin) (Table 34.2;
see also Figure 34.1). These hormones are essential for
the regulation of growth, reproduction and some meta
bolic processes. Deficiency or overproduction of these
hormones disrupts this regulation.
The anterior pituitary hormones are released in a
rhythmic manner into the bloodstream. Their secre
tion varies with time of day (often referred to as
diurnal
rhythm
) or with physiological conditions such as exercise
or sleep. Their release is affected by activity in the CNS;
by hypothalamic hormones; by hormones of the periph
eral endocrine glands; by certain diseases that can
alter endocrine functioning; and by a variety of drugs,
which can directly or indirectly upset the homeostasis
in the body and cause an endocrine response. Normally,
diurnal rhythm occurs when the hypothalamus begins
secretion of corticotropin-releasing factor (CRF) in the
evening, peaking at about midnight; adrenocortical
peak response is between 6 and 9 a.m.; levels fall during
the day until evening, when the low level is picked up by
the hypothalamus and CRF secretion begins again.
The anterior pituitary also produces melanocyte-
stimulating hormone (MSH) and various lipotropins.
MSH plays an important role in animals that use skin
colour changes as an adaptive mechanism. It might
also be important for nerve growth and development in
humans. Lipotropins stimulate fat mobilisation but have
not been clearly isolated in humans.
The posterior pituitary
The
posterior pituitary
stores two hormones that
are produced by the hypothalamus and deposited in
the posterior lobe via the nerve axons where they are
produced. These two hormones are ADH, also referred
to as vasopressin and oxytocin. ADH is directly released
in response to increased plasma osmolarity or decreased
blood volume (which often results in increased osmolar
ity). The osmoreceptors in the hypothalamus stimulate
the release of ADH. Oxytocin stimulates uterine smooth
muscle contraction in late phases of pregnancy and also
causes milk release or “let down” reflex in breastfeeding
women. Its release is stimulated by various hormones
and neurological stimuli associated with labour and
with breastfeeding.
The intermediate lobe
The intermediate lobe of the pituitary produces endor
phins and encephalins, which are released in response
to severe pain or stress and occupy specific endorphin-
receptor sites in the brainstem to block the perception of
pain. These hormones are also produced in peripheral
tissues and in other areas of the brain. They are released
in response to overactivity of pain nerves, sympa
thetic stimulation, transcutaneous stimulation, guided
imagery and vigorous exercise.
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TABLE 34.2 Hypothalamic hormones, associated anterior pituitary hormones and target organ response
Hypothalamus hormones
Anterior pituitary hormones
Target organ response
Stimulating hormones
CRH (corticotropin-releasing
hormone)
ACTH (adrenocorticotropic hormone)
Adrenal corticosteroid hormones
TRH (thyroid-releasing hormone)
TSH (thyroid-stimulating hormone)
Thyroid hormone
GHRH (growth hormone-releasing
hormone)
GH (growth hormone)
Cell growth
GnRH (gonadotropin-releasing
hormone)
LH and FSH (luteinising hormone,
follicle-stimulating hormone)
Oestrogen and progesterone
(females), testosterone (males)
PRH (prolactin-releasing hormone)
Prolactin
Milk production
MSH (melanocyte-stimulating
hormone)
Melanin stimulation (colour change in
animals, nerve growth in humans)
Inhibiting hormones
Somatostatin (growth hormone-
inhibiting factor)
Stops release of GH
PIF (prolactin-inhibiting factors)
Stops release of prolactin
