Pharmacology – III
PHL-418
Endocrine system Introduction
Hypothalamic and Pituitary Hormones
Dr. Hassan Madkhali
Assistant Professor
Department of Pharmacology
E mail: h.madkhali@psau.edu.sa
Content Layout with List
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ENDOCRINE SYSTEM INTRODUCTION
CLASSES OF HORMONES
SOURCES OF HORMONES
HYPOTHALAMIC AND ANTERIOR
PITUITARY HORMONES
• HORMONES OF THE POSTERIOR
PITUITARY
The
Endocrine System
• The endocrine system controls many body functions
– Exerts control by releasing special chemical substances into the blood
called hormones
– Hormones affect other endocrine glands or body systems
The neuroendocrine system, which is controlled by the pituitary and
hypothalamus, coordinates body functions by transmitting messages
between individual cells and tissues. This contrasts with the nervous
system, which communicates locally through electrical impulses and
neurotransmitters directed through neurons to other neurons or to
specific target organs, such as muscle or glands.
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HORMONE: A substance that is released in one tissue and
travels through the circulation (usually) to the target tissue.
Hormones reach all parts of the body, but only target cells
are equipped to respond
Hormones are secreted in small amounts and often in
bursts (pulsatile secretion)
Endocrine
System
Functions:
• Maintain Internal
Homeostasis
• Support Cell Growth
• Coordinate
Development
• Coordinate
Reproduction ,
fertility, sexual
function
• Facilitate Responses
to External Stimuli
Four Classes of Hormones:
• Peptide/ Protein (Range from 3 amino acids to hundreds of
amino acids in size. )
• Steroid
• Amine (Thyroid hormones and
Catecholamines)
• Eicosanoid (Fatty acid derivatives )
Location of receptors:
• On cell surface: Peptides and
proteins
• In cytoplasm: Steroids
• In nucleus: Thyroid hormones
Classification of hormones
based on their solubility
 The hormones fall into two general
classes based on their solubility in
water.
 The water soluble { amine and
peptide/protein hormones} are
secreted by exocytosis, travel freely
in the bloodstream, and bind to cellsurface receptors.
 The lipid soluble hormones {
thyroid hormone, steroid hormones
and Vitamin D3}. diffuse across cell
membranes, travel in the
bloodstream bound to transport
proteins, and diffuse through the
membrane of target cells .
Fat-soluble
hormone
Watersoluble
hormone
Signal receptor
TARGET
CELL
(a)
Transport
protein
Signal
receptor
NUCLEUS (b)
Mechanisms of endocrine disease
• Hormone deficiency treated with Hormone replacement therapy
(HRT)
• Hormone excess treated with Specific antagonists or release
inhibitors.
• Hormone resistance treated with Sensitizers
Sources of hormones:
- Natural:
Human (GH; LH & FSH; hCG);
Animal (Insulin, T3 & T4)
- Biosynthetic:
Insulin (Porcine & Bovine)
- Synthetic: Most hormones and their antagonists
DNA recombinant technology
Hypothalamic &
Pituitary Hormones
HYPOTHALAMIC AND ANTERIOR PITUITARY HORMONES
 The hormones secreted by the hypothalamus and the pituitary are all
peptides or low molecular weight proteins that act by binding to
specific receptor sites on their target tissues. The hormones of the
anterior pituitary are regulated by neuropeptides that are called either
“releasing” or “inhibiting” factors or hormones. These are produced in
the hypothalamus, and they reach the pituitary by the hypophyseal
portal system.
 Each hypothalamic regulatory hormone controls the release of a
specific hormone from the anterior pituitary.
 Hormones of the anterior and posterior pituitary are administered
intramuscularly (IM), subcutaneously, or intranasally because their
peptidyl nature makes them susceptible to destruction by the
proteolytic enzymes of the digestive tract.
A. Adrenocorticotropic hormone (corticotropin)
Mechanism of action:
ACTH binds to receptors on the
surface of the adrenal cortex, thereby
activating G protein–coupled
processes that ultimately stimulate the
rate-limiting step in the
adrenocorticosteroid synthetic pathway
(cholesterol to pregnenolone)
Therapeutic uses:
As a diagnostic tool for differentiating
between primary adrenal insufficiency
(Addison disease, associated with
adrenal atrophy) and secondary
adrenal insufficiency (caused by the
inadequate
secretion of ACTH by the pituitary).
Adverse effects: Short-term use of
ACTH is usually well tolerated. With
longer use, toxicities are similar to
those of glucocorticoids and include
hypertension, peripheral edema,
hypokalemia, emotional disturbances,
and increased risk of infection.
B. Growth hormone (somatotropin)
GH is released in a pulsatile manner, with the highest
levels occurring during sleep. Somatotropin influences a
wide variety of biochemical processes (for example, cell
proliferation and bone growth are promoted)
Mechanism of action: Although many physiologic effects
of GH are exerted directly at its targets, others are
mediated through the
somatomedins—insulin-like growth factors 1 and 2 (IGF-1
and IGF-2).
Therapeutic uses:
Somatropin is used in the treatment of GH deficiency or
growth failure in children. Somatropin is administered by
subcutaneous or IM injection. Although the half-life of GH
is short (approximately 25 minutes), it induces the release
of IGF-1 from the liver, which is responsible for
subsequent GH-like actions.
Adverse effects: Adverse effects of somatropin include
pain at the injection site, edema, arthralgias, myalgias, flulike symptoms, and an increased risk of diabetes.
C. Somatostatin (Growth hormoneinhibiting hormone)
In the pituitary, somatostatin binds to receptors that suppress GH and
thyroid-stimulating hormone release.
Somatostatin not only inhibits the release of GH but also that of insulin,
glucagon, and gastrin.
Octreotide and lanreotide are synthetic analogs of somatostatin. Their
half-lives are longer than that of the natural compound, and depot
formulations are available, allowing for administration once every 4
weeks.
They have found use in the treatment of acromegaly and in diarrhea and
flushing associated with carcinoid tumors.
Adverse effects of octreotide include diarrhea, abdominal pain, flatulence,
nausea, and steatorrhea. Gallbladder emptying is delayed, and
asymptomatic cholesterol gallstones can occur with long-term treatment.
D. Gonadotropin-releasing hormone
Pulsatile secretion of gonadotropin-releasing hormone
(GnRH) from the hypothalamus is essential for the release
of the gonadotropins follicle stimulating hormone (FSH) and
luteinizing hormone (LH) from the anterior pituitary.
However, continuous administration of GnRH inhibits
gonadotropin release through down-regulation of the GnRH
receptors on the pituitary.
Continuous administration of synthetic GnRH analogs, such
as leuprolide, goserelin, nafarelin, and histrelin, is effective
in suppressing production of the gonadotropins
Suppression of gonadotropins, in turn, leads to reduced
production of gonadal steroid hormones (androgens and
estrogens).
Thus, these agents are effective in the treatment of
prostate cancer, endometriosis, and precocious puberty.
They are contraindicated in pregnancy and breast-feeding.
E. Gonadotropins
The gonadotropins (FSH and LH) are glycoproteins that are produced
in the anterior pituitary.
The regulation of gonadal steroid hormones depends on these agents.
They find use in the treatment of infertility.
Menotropins (also known as human menopausal gonadotropins or
hMG) are obtained from the urine of postmenopausal women and
contain both FSH and LH.
Urofollitropin is FSH obtained from postmenopausal women and is
devoid of LH.
Follitropin alfa and follitropin beta are human FSH products
manufactured using recombinant DNA technology.
Human chorionic gonadotropin (hCG) is a placental hormone that is
excreted in the urine of pregnant women.
The effects of hCG and choriogonadotropin alfa (made using recombinant DNA technology)
are essentially identical to those of LH.
All of these hormones are injected via the IM or subcutaneous route.
F. Prolactin
Prolactin is a peptide hormone that is also secreted by the anterior
pituitary.
Its primary function is to stimulate and maintain lactation.
Its secretion is inhibited by dopamine acting at D2 receptors.
Drugs that act as dopamine antagonists (for example, metoclopramide and
antipsychotics such as risperidone) can increase the secretion of prolactin.
Hyperprolactinemia, which is associated with galactorrhea and
hypogonadism, is treated with D2 receptor agonists, such as bromocriptine
and cabergoline. Both of these agents also find use in the treatment of
pituitary microadenomas.
HORMONES OF THE
POSTERIOR PITUITARY
 In contrast to the hormones of
the anterior lobe of the pituitary,
those of the posterior lobe,
vasopressin and oxytocin, are
not regulated by releasing
hormones. Instead, they are
synthesized in the hypothalamus,
transported to the posterior
pituitary,
and
released
in
response to specific physiologic
signals, such as high plasma
osmolarity or parturition.
 Both hormones are administered intravenously
and have very short half-lives.
A. Oxytocin
Oxytocin is used in obstetrics to stimulate uterine contraction and induce labor.
Oxytocin also causes milk ejection by contracting the myoepithelial cells around
the mammary alveoli.
B. Vasopressin
Vasopressin (antidiuretic hormone) is structurally related to oxytocin. Vasopressin
has both antidiuretic and vasopressor effects.
In the kidney, it binds to the V2 receptor to increase water permeability and
reabsorption in the collecting tubules. Thus, the major use of vasopressin is to treat
diabetes insipidus.
Other effects of vasopressin are mediated by the V1 receptor, which is found in
liver, vascular smooth muscle (where it causes constriction), and other tissues.
Desmopressin, an analog of vasopressin, has minimal activity at the V1 receptor,
making it largely free of pressor effects. This analog is longer acting than
vasopressin and is preferred for the treatment of diabetes insipidus and nocturnal
enuresis. For these indications, desmopressin may be administered intranasally or
orally.
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