ENDOCRINE
PHARMACOLOGY
Introduction to the Endocrine
System
Major Functions of the Endocrine System:
1) Maintain internal body homeostasis (cellular metabolism,
regulation of body fluids and electrolytes, modulation of the
immune function).
2) Coordinate various functions of the body (Reproduction,
responses to external stimuli, circadian rhythm).
3) Support cell growth and development.
• These functions were achieved by secretion of chemical mediators
(Hormones).
Chemical substance synthesized/released (in response to specific stimuli)
in small amounts by an endocrine tissue and carried by blood to the target
tissue.
Structures of the Endocrine System
• The system consists of glands (major player), cells, tissues, and
organs.
• Endocrine Glands: Pituitary, Thyroid, Parathyroids,
Adrenals, and Pineal glands.
• Organs with secondary endocrine function: Hypothalamus,
Thymus, Heart, Kidneys, Stomach, Small intestine, Liver, and
Gonads contain cells with endocrine function.
• The Pancreas functions as both exocrine and endocrine gland.
• The Placenta of pregnant mammals also produces hormones that
influence uterine, fetal, and ovarian processes.
What is a gland?
• Is specialized cell clusters which produces and releases
chemical products/mediator that perform a specific
function in the body.
• There are two types of gland:
Endocrine glands: ductless glands produces/releases
hormones into the vascular system to be carried out by the
blood to other place in the body.
Exocrine glands: (e.g. sweat glands, lymph nodes), produces
and releases their products (non-hormonal) through a duct to
act within the near environment.
• Chemistry of Hormones:
Amines (Thyroxine, Epinephrine).
Proteins (Insulin, GH, Glucagon).
Peptides (ADH and Oxytocin).
Glycoproteins (FSH, LH).
Steroids (Cortisol, Aldosterone, Estrogens, Testosterone).
• Hormone molecules can also be divided to:
Polar or water-soluble (cannot or poorly pass through plasma
membranes).
Nonpolar or water-insoluble and often referred to as lipophilic
hormones (penetrate the plasma membrane easily).
Hormones Release and Transport:
• Hormones could be released directly to the blood, or diffuse into
the bloodstream after secretion on extracellular space.
• The blood carries hormones to the target tissue cells which
contain specific receptors that bind the hormones and give the
response.
• Water-soluble hormones are soluble in the bloodstream.
• Lipid-soluble hormones are not soluble in blood. They are
associated with Carrier Proteins via reversible bonds, allowing
transport through the circulation.
T4 and T3 are transported through thyroxine-binding globulin (TBG).
Corticosteroids transported by corticosteroid-binding globulin (CBG).
Hormone Receptors:
1) Membrane-Associated Receptors
Bind hydrophilic hormones on the cell surface.
Transmit signals into the cell through activation of second messenger or
by intracellular enzyme activity.
E.g. FSH, LH, Epinephrine, and Insulin Receptors.
2) Intracellular Receptors:
Bind hydrophobic hormones.
Hormone-receptor complex could migrate to the nucleus where they could
modulate the transcription of specific genes.
Modulation of gene transcription induce synthesis or inhibit synthesis of
some proteins.
E.g. Thyroid hormones, Cortisol and Estrogen.
Regulation of Hormones Secretion
• Feedback Loops:
Positive Feedback: stimulation of hormone secretion in response to
other hormones that circulated in the blood or to its original release.
Negative Feedback: inhibition of hormone secretion in response to
other hormones that circulated in the blood or when it exerts its effects.
• Endocrine Stimuli:
Humoral stimuli: release/inhibition of hormones in response to
changes in blood levels of non-hormone chemicals.
Neural stimuli: release/inhibition of hormones in response to the
nervous system.
• It may be complex (Prolactin production is affected by many
neurotransmitters and hormones).
E.G. Feedback Loops
• Release of Oxytocin during childbirth:
The first contractions of the uterus signal the body to release oxytocin (travels to the
uterus and stimulates more contractions).
Released oxytocin signal the body to release more, which stimulates more contractions.
The feedback loop continues until the child is born—the contractions stop, signalling the
body to stop releasing oxytocin.
• The TRH (hypothalamus)-TSH (pituitary)-Thyroxine (thyroid) system:
Drop of thyroxine levels below normal signals the hypothalamus to release TRH.
Released TRH signals the pituitary to release TSH.
TSH then stimulates the thyroid to produce thyroxine.
High levels of thyroxine in the blood signal the hypothalamus to stop releasing TRH.
E.G. Endocrine Stimuli
• Humoral stimuli:
Secretion of Insulin in response to high level of blood glucose.
Secretion of Parathyroid Hormone in response to low blood calcium
level.
• Neural stimuli:
Release of Adrenaline in response to activation of the fight-or-flight
response by the sympathetic nervous system.
Detection of light by the sensory receptors on the retina of the eyes inhibit
Pineal Gland secretion of Melatonin (when the environment grows dark,
melatonin production is stimulated).
Pulsatile Secretion of Hormones:
• Is a biochemical phenomenon in which the hormone
secreted in a regular temporal pattern.
• Pulsatility can be critical to the function of many
hormones to maintain the delicate homeostatic balance
necessary for essential life processes.
• Variations of the concentration in a certain frequency
(constant stimulation) can cause functional inhibition of
the receptor due to profound downregulation.
HYPOTHALAMUS - PITUITARY COMPLEX
• This complex can be thought of as the command center of
the endocrine system.
• It also coordinates the messages of the endocrine and
nervous systems.
• Consists of:
Hypothalamic Hormones.
Anterior Pituitary Hormones.
Posterior Pituitary Hormones.
HYPOTHALAMUS
• Is a small structure located near the base of the brain.
• It affects the endocrine system through production of six
major hormones.
These hormones stimulate/inhibit the release of hormones
made in the anterior pituitary (also called hypothalamic
regulatory factors).
• Also produces two hormones (Vasopressin and
Oxytocin).
Produced by the hypothalamus, transported to the posterior
lobe of the pituitary gland for storage and subsequent release.
HYPOTHALAMIC HORMONES:
1. Somatotropin-Releasing Hormone (Growth Hormone-
Releasing Hormone).
2. Somatotropin-Release Inhibiting Hormone
(Somatostatin).
3. Thyrotropin-Releasing Hormone (Protirelin).
4. Corticotropin-Releasing Hormone.
5. Prolactin Inhibiting Hormone (Dopamine).
6. Gonadotropin-Releasing Hormone (GnRH).
PITUITARY GLAND
• Small, oval structure located under the brain.
• It has two parts:
• The anterior lobe (Adenohypophysis):
Produce and release six hormones that influences the
activity of many other endocrine glands, tissues or
organs.
• The posterior lobe (Neurohypophysis):
• Stores and release two hypothalamus hormones.
ANTERIOR PITUITARY HORMONES:
• Secretion may be controlled by hypothalamic regulatory
factors or other hormones that circulated in the blood.
• All anterior pituitary hormones are released into the
bloodstream in a pulsatile manner (by the pulsatile
secretion of hypothalamic regulatory hormones).
• Secretion may also varies with time of day or
physiological conditions.
1) Growth Hormone (Somatotropin):
• Stimulate linear body growth and regulate cellular metabolism.
• Stimulates lipolysis, elevates blood glucose, and promotes protein
synthesis by:
Direct effect on many tissues.
Stimulation of hepatic production of insulin-like growth factors
(IGFs/Somatomedins) which mediate anabolic actions on many cell.
• Secretion is regulated by GHRH and Somatostatin.
• Release of IGFs has an inhibitory effect on GH secretion by stimulating
Somatostatin release from the hypothalamus.
• Secretion is high in the newborn, decreasing at 4 years to an
intermediate level, maintained until after puberty, then it decline to
low levels.
2) Thyrotropin (Thyroid stimulating hormone - TSH):
• Stimulates the thyroid gland to produce thyroid hormones
(Thyroxin and T3).
3) Corticotropin (Adrenocorticotropic hormone -
ACTH):
• Stimulates production of Glucocorticoids and
Mineralocorticoids from the Adrenal Cortex.
4) Prolactin:
• Initiates and maintains milk production by the mammary
glands in the breast.
5) Gonadotropins (FSH and LH):
• Follicle-Stimulating Hormone (FSH or Folliculotropin):
Females: Released during the follicular phase of the menstrual cycle,
required for development of ovarian follicles and for estrogen synthesis
from the ovaries.
Males: Stimulates spermatogenesis and synthesis of androgen-binding
proteins in the testes.
• Luteinizing Hormone (LH or Luteotropin):
Females: Secretion occurs just before ovulation to induce ovulation,
progesterone and androgen synthesis in the cells of the ovaries.
Males: Stimulates testosterone production from testes cells.
• Production of LH and FSH is mainly controlled by GnRH from the
hypothalamus, and Inhibin (produced by gonads).
POSTERIOR PITUITARY HORMONES:
• Synthesized in the hypothalamus and transported to the posterior
lobe of the pituitary gland for storage and subsequent release.
1) Vasopressin (Antidiuretic Hormone, ADH):
Released in response to decreases in blood volume.
Acts on the kidney causing increased water reabsorption (V2 receptors).
At higher concentrations, acts on V1 receptors to cause a general
constriction of most blood vessels.
2) Oxytocin:
Stimulates contraction of uterine smooth muscle in late phase of
pregnancy.
Causes milk release from lactating mammary glands.