ENDOCRINAL SYSTEM
Dr. Sachin Rathod,
MD Physiology,
Professor.
ORGANIZATION OF ENDOCRINE
SYSTEM
• The biological functions of the multicellular living organisms are very well coordinated.
• This co-ordination is achieved by two main control systems, the nervous system and the endocrinal system.
• The endocrinal system consists of various endocrine glands and neurosecretory cells located in the
hypothalamus.
1. Pituitary gland (hypophysis):
• It has two main parts: adenohypophysis and neurohypophysis.
• Adenohypophysis secretes:
• Growth hormone (GH) or somatotropins,
• Follicle-stimulating hormone (FSH),
• Luteinizing hormone (LH),
• Prolactin,
• Thyrotropin or thyroid stimulating hormone (TSH) and
• corticotropin or adrenocorticotropic hormone (ACTH).
• The neurohypophysis stores the:
• Antidiuretic hormone (ADH) or vasopressin
• Oxytocin
2. Thyroid gland.
• The thyroid gland is present in the neck in front of the trachea.
• It secretes thyroxine (T4) and triiodothyronine (T3).
• The C cells or parafollicular cells secrete calcitonin.
3. Parathyroid glands.
• These are four in number, very small glands situated behind the lobes of the thyroid gland.
• Secrete parathormone.
4. Adrenal glands.
• These are situated on the upper poles of the two kidneys, hence also called suprarenal glands.
• The outer cortex:
• Cortisol,
• Aldosterone,
• Sex steroids and
• The inner medullary:
• Catecholamines (adrenaline and noradrenaline).
5. Pancreatic islets (islets of Langerhans):
• These are small groups of cells,
• Insulin,
• Glucagon
• Somatostatin.
6. Gonads.
• These include ovaries in females and testes in males.
• The ovaries secrete oestrogens and progesterone
• Testes secrete testosterone.
7. Pineal gland.
• It is a small gland present in the roof of third ventricle in the brain. It secretes melatonin and other biogenic
amines.
8. Placenta.
• During pregnancy, placenta secretes various hormones like
• Human chorionic gonadotropin (HCG), oestrogen, progesterone, somatotropins and relaxin.
9. Gastrointestinal mucosa
• Gastrointestinal (GI) hormones,
• e.g. gastrin, secretin, cholecystokinin–pancreozymin (CCK-PZ), etc.
10. Kidneys.
• Erythropoietin, prostaglandins and 1,25-dihydroxycholecalciferol, Renin.
11. Atrial muscle cells.
• These secrete atrial natriuretic peptides (ANP) and many other peptides.
12. Skin.
This is also considered to act as an endocrine structure by producing vitamin D.
GENERAL PRINCIPLES OF
ENDOCRINAL SYSTEM
• Hormones are secretory products of the
ductless glands, which are released in
catalytic amounts into the blood stream
and transported to specific target cells
(or organs), where they elicit
physiologic, morphologic and
biochemical responses.
• Endocrine hormones
• Neurocrine hormones
• Paracrine hormones.
• Autocrine hormones.
CLASSIFICATION OF HORMONES
A. Depending upon the chemical nature B. Depending upon the mechanism of action
• Amines or amino acid derivatives: • Group I hormones:
• Catecholamines (epinephrine and • These act by binding to intracellular receptor
norepinephrine) • Mediate their actions via formation of a
• Thyroxine (T4) and Triiodothyronine (T3). hormone–receptor complex.
• Proteins and polypeptides: • E.g. steroid, retinoid and thyroid hormones.
• Posterior pituitary hormones, • Group II hormones.
• Insulin, • These involve second messenger to mediate
• Glucagon, their effect.
• Parathormone and • Depending upon the chemical nature of the
• second messengers, group II hormones are
Other anterior pituitary hormones.
further divided into four subgroups: A, B, C and
• Steroid hormones: D
• Glucocorticoids, • A- Cyclic AMP (cAMP)
• Mineralocorticoids, • B- Cyclic GMP (cGMP)
• Sex steroids and • C- Calcium or phosphatidyl inositol or both
• D- Kinase or phosphatase cascade
• Vitamin D.
HORMONE TRANSPORT, PLASMA
CONCENTRATION & HALF-LIFE
Hormone transport:
• Unbound form:
• Some hormones circulate as free molecule,
• e.g. catecholamines and most peptide and protein hormones
• Bound form:
• Some hormones, such as steroids, thyroid hormones and vitamin D circulate
bound to specific globulins
• Advantages :
• Protects the hormone against clearance by the kidney,
• Slows down the rate of degradation by the liver and
• Provides circulating reserve of the hormone.
Plasma concentration:
• Hormones are usually secreted
into the circulation in extremely
low concentrations
Half Life:
• Peptide hormones have a short
half-life.
• Steroids and thyroid hormones
have significantly longer half-life
because they are bound to the
plasma proteins.
FUNCTIONS OF HORMONES
• Hormones regulate existing fundamental processes.
• Regulation of biochemical reactions:
• They stimulate or inhibit the rate and magnitude of biochemical reactions by
controlling enzymes and thereby cause morphologic, biochemical and
functional changes in target tissues.
• They modulate energy producing processes and regulate the circulating
levels of energy-yielding substances.
• Regulation of bodily processes:
• Hormones regulate different bodily processes, such as growth, maturation,
differentiation, regeneration, reproduction and behavior.
HORMONE DISPOSAL
• Target cell uptake and intracellular degradation:
• Degradation of protein and amine hormones occurs after binding to membrane receptors
and then internalization of hormone–receptor complex.
• Degradation of thyroid and steroid hormones occurs after binding the hormone–receptor
complex to the chromatin.
• Metabolic degradation/inactivation:
• Proteolysis
• Oxidation
• Reduction
• Hydroxylation
• Decarboxylation
• Methylation
• Glucuronization
• Sulfation
REGULATION OF HORMONE
SECRETION
1. Feedback control
2. Neural control
3. Chronotropic control
FEEDBACK CONTROL
• Negative feedback control:
• The influence of blood
concentration of the hormone or
its effect is to inhibit further
secretion of the hormone and is
called negative feedback control.
• Positive feedback control:
• Amplify the initial biological
effects of the hormone.
• Mechanisms:
• Hormone–hormone feedback and
• Substrate–hormone feedback.
Hormone–hormone feedback control
• Long-loop feedback:
• The peripheral gland hormone can exert long-loop negative
feedback control on both the hypothalamus and the
anterior lobe of pituitary.
• Short-loop feedback:
• The pituitary tropic hormones decrease the secretion of
hypophysiotropic hormone by short-loop feedback.
• Ultra-short-loop feedback:
• The hypophysiotropic hormones may inhibit their own
synthesis and secretion via an ultra-short-loop feedback
mechanism.
Substrate–hormone feedback control
• Regulation of insulin secretion from the pancreatic beta
cells of the islets of Langerhans and glucagon secretion
from the alpha cells by blood glucose levels.
NEURAL CONTROL
External stimuli:
• Modulate hormone release through neural mechanisms, may be visual,
auditory, olfactory, gustatory and tactile.
Internal stimuli:
• Influence hormonal release through neural mechanism, include pain, emotion,
sexual excitement, fright, stress and changes in blood volume.
• Neural control depending upon the type of nerve fibres involved may be:
• Adrenergic
• Cholinergic
• Dopaminergic
• Serotonergic
• GABAergic
CHRONOTROPIC CONTROL
• Oscillating or pulsating release
• Diurnal Variation
• Menstrual rhythm
• Seasonal rhythm
• Developmental rhythm
HORMONE RECEPTORS
• Large proteins in hormone sensitive target cells.
Characteristics:
• Specificity: There is specific receptors for each hormone.
• Location:
• Internal: located inside the cell. Like steroid & thyroid hormones receptors
located inside the nucleus.
• External: Located on cell membrane. Peptide & amine hormones.
• Regulation of receptor numbers:
• Down regulation
• Up regulation
MECHANISM OF ACTION OF
HORMONE
• Action through change in membrane permeability
• Action through effect on gene expression by binding of hormones with
intracellular receptors
• Action through second messengers
• Action of hormone via tyrosine kinase activation
ACTION THROUGH CHANGE IN
MEMBRANE PERMEABILITY
• Certain hormones bind with the receptors present in the cell membrane
• Cause conformational change in the protein of the receptors, this results
into either opening or closing of the ions channels
• The movement of ions through Ca2+ channels causes the subsequent
effect,
• E.g. adrenaline, noradrenaline act by this mechanism.
EFFECT ON GENE EXPRESSION
• Group I hormones act by their effect on the gene expression
include steroid hormones, retinoids and thyroid hormones.
• Sequence of events:
• Transport: After secretion, the hormone is carried to the target
tissue on serum binding protein.
• Internalization: Being lipophilic, the hormone easily diffuses
through the plasma membrane.
• Receptor–hormone complex: It is formed by binding of hormone to
the specific receptor inside the cell. Conformational change occurs in
the receptor proteins leading to activation of receptors.
• Diffusion: The activated receptor–hormone complex then diffuses
into the nucleus and binds on the specific region on the DNA known
as hormone responsive element (HRE), which initiates gene
transcription.
• Binding of the receptor–hormone complex to DNA alters the rate of
transcription of messenger RNA (mRNA).
• mRNA promotes the translation process at the ribosomes.
ACTION THROUGH SECOND
MESSENGERS
• The peptides and biogenic amines are two principal classes of
hormones which act through second messenger and are
classified as group II hormones.
• Coupling by G-proteins
• The hormone bearing receptor then interacts with a G-protein and
activates it by binding GTP.
• There are two classes of G-proteins:
• Stimulatory G-protein (Gs)
• Inhibitory G-protein (Gi).
• The G-protein interacts with one or more of the effector protein to
activate or inhibit them.
• Generate second messenger that mediates the hormone’s
intracellular action.
• Second messenger systems:
• Adenylyl cyclase–cAMP system,
• Guanyl cyclase–cGMP system,
• Membrane phospholipase–phospholipid system and
• Calcium–calmodulin system.
ADENYLYL CYCLASE–CAMP
SYSTEM
• The hormones which act through this system
constitute the group IIA hormones.
• Binding of hormone to a specific receptor in the cell
membrane.
• Activation of G-protein:
• The GDP is released from the G-protein and is replaced
by GTP, i.e. G-protein is activated.
• Activation of enzyme adenylyl cyclase:
• Stimulates or inhibits the enzyme adenylyl cyclase.
• Formation of cAMP:
• Catalyzes the formation of cAMP from cytoplasmic ATP
with Mg2+ as cofactor.
• Action of cAMP:
• Stimulates a cascade of enzyme activation.
GUANYLATE CYCLASE–CGMP
SYSTEM
• Group II-B hormones - atrial natriuretic factor and nitric oxide
• Synthesis of cyclic GMP
• cGMP exerts its biochemical response through an enzyme protein kinase
G.
MEMBRANE PHOSPHOLIPASE–
PHOSPHOLIPID SYSTEM OR IP3
MECHANISM
• Group II-C hormones
• Hormone binds to a receptor in the plasma membrane.
• The hormone–receptor complex via a G-protein activates the
membrane enzyme phospholipase C.
• Activated phospholipase C then releases diacylglycerol and
inositol triphosphate (IP3) from the membrane phospholipid.
• Inositol triphosphate (IP3) then mobilizes Ca2+ from the
endoplasmic reticulum.
• Calcium ions (Ca2+) and diacylglycerol together activate
protein kinase C.
• Activated protein kinase C phosphorylates proteins and
causes specific physiological action.
• Diacylglycerol also yields arachidonic acid, which serves as a
substrate for rapid synthesis of prostaglandins that modulate
cell response.
CALCIUM–CALMODULIN SYSTEM
• Group-II C hormone
• Hormone binds to a specific receptor in the
plasma membrane.
• The hormone–receptor complex, via G-protein
opens the Ca2+ channels on the cell membrane
and also activates mobilization of Ca2+ bound to
the endoplasmic reticulum.
• Ca2+ binds to a specific binding protein the
calmodulin in various proportions.
• The different calcium–calmodulin complexes
activate or deactivate various calcium-
dependent enzymes producing different
physiological actions.
TYROSINE KINASE ACTIVATION
• Group-II D hormones
• These receptors have an extracellular hormone binding portion, a single
transmembrane portion and an intracytoplasmic C-terminal portion.
• Hormone receptors possessing intrinsic tyrosine activity:
• Receptor autophosphorylation at specific tyrosine sites.
• The receptor itself becomes a tyrosine kinase that phosphorylates tyrosine
residue on the intracellular protein substrates.
• A cascade of events leading to an enzyme activation and gene
transcription.
• Hormone receptors do not possessing intrinsic tyrosine activity:
• Hormone binding to extracellular portion of the receptor changes its
intracytoplasmic tail.
• Tail of receptor exposes sites which attract and dock the intracytoplasmic
tyrosine kinases.
• The activated intracytoplasmic tyrosine kinases phosphorylate
cytoplasmic substrates, such as transcription factor proteins and
ultimately modulate gene expression.
MEASUREMENT OF HORMONES
• Bioassay:
• Injecting the unknown sample of plasma in the experimental animals and
observing quantitatively the specific biological effect.
• Immunoassay:
• Radioimmunoassay (RIA)-
• Enzyme-linked immunosorbent assay (ELISA).
• Cytochemical assay and
• Dynamic tests:
• Suppression type of dynamic tests
• Stimulation type of dynamic tests
Thank you very much
