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INTRODUCTION

TO
ENDOCRINE PHYSIOLOGY
Dr. Mohamed Smith
OUTLINE

• Introduction
• Classification of hormones
• Hormone interactions
• Mechanism of action of hormones
• Endocrine system
INTRODUCTION
• Endcocrinology: It is study of homeostatic functions of
substances called HORMONES, that are released from glands
called endocrine glands distributed throughout the body.

• The multiple activities of the cells, tissues and organs of the


body are coordinated by the interplay of several types of
chemical messenger systems.
1. NEUROTRANSMITTERS- They are released by axon
terminals of neurons into the synaptic junctions and act
locally to control nerve cell functions

2. ENDOCRINE HORMONES- They are released by glands or


specialized cells into the circulating blood and influence the
function of target cell at another location in the body.

3. NEUROENDCRINE- They are secreted by neurons into the


circulating blood and influence the function of target cells at
another location in the body.
INTRODUCTION
• 4. PARACRINES- They are secreted by cells into the
extracellular fluid and affect neighboring target cells of different
type.

• 5 AUTOCRINES- They are secreted by cells into the


extracellular fluid and affect the function of the same cells that
produced them.

• 6. CYTOKINES- These are hormones secreted by cells into the


extracellular fluid and can function as autocrines,
paracrines or endocrine hormones. Egs: interleukins
• Endocrine glands – pituitary, thyroid, parathyroid,
adrenal, pineal, and thymus
• The pancreas and gonads produce both hormones and
exocrine products
• The hypothalamus has both neural functions and releases
hormones
• Other tissues and organs that produce hormones –
adipose cells, pockets of cells in the walls of the small
intestine, stomach, kidneys, and heart
CLASSIFICATION OF HORMONES

• Hormones are classified based on their chemical structure

1. AMINES: are hormones derived from 2 amino acids


(tryptophan and tyrosine)
e.g
- Thyroid gland : T3 and T4.
- Pineal gland : melatonin.
- Adrenal medulla: epinephrine and norepinephrine.

2. POLYPEPTIDES: They contain less than 100 amino acids


and are water soluble e.g ADH
3. PROTEINS: They contain more than 100 amino acids e.g
Growth hormone.

4. GLYCOPROTEINS: consist of polypeptides with one or more


carbohydrate groups e.g:
follicle stimulating hormone (FSH),
Luteinizing hormone (LH) and
Thyroid stimulating hormone (TSH).

5. STEROIDS are lipids derived from cholesterol e.g progesterone,


testosterone, estradiol,
cortisol, aldosterone.
PROHORMONES AND PREHORMONES

• PREHORMONES -The term prehormone designates large molecules secreted by


endocrine glands but are inactive until they are changed into active form in their
target cell
e.g. thyroxine (T4) is inactive until converted to T3 in target cells
T4 (inactive) T3 (active)
Vit D3 (2 hydroxylation) 1,25 dihydroxyvit D3 (active).

• PROHORMONES – These are small precursors molecules derived from the


cleavage of prehormones
– e.g. proinsulin is cut and spliced together to form insulin.
Control of Hormone Release

• Blood levels of hormones:


• Are controlled by negative and positive feedback systems
• Vary only within a narrow desirable range
• Hormones are synthesized and released in response to humoral,
neural, and hormonal stimuli
Feedback Control

• Negative feedback is most common: for example, LH from


pituitary stimulates the testis to produce testosterone which in
turn feeds back and inhibits LH secretion

• Positive feedback is less common: examples include LH


stimulation of estrogen which stimulates LH surge at ovulation
HORMONE INTERACTIONS

1. SYNERGISTIC – The interaction of two or more hormones to produce


a combined effect greater that the sum of their separate effects.
e.g
-Norepinephrine and epinephrine on heart rate
-Estrogen, cortisol, prolactin, have complimentary effect on mammary
glands to produce and secret milk.

2. PERMISSIVE EFFECT – one hormone enhances the responsiveness


of a target organ to a second hormone.
– e.g. estradiol induces formation of receptors for progesterone.
HORMONE INTERACTIONS

3. ANTAGONISTIC – action of one inhibits the effect


of the other
– e.g. pancreatic islets secrete Insulin and Glucagon.
Circulating transport
Protein
Principle Hormone
Transport Protein Transported

Specific
Corticosteroid binding globulin Cortisol, aldosterone
(CBG, transcortin)
Thyroxine binding globulin (TBG) Thyroxine, triiodothyronine
Sex hormone-binding globulin Testosterone, estrogen
(SHBG)
Nonspecific
Albumin Most steroids, thyroxine,
triiodothyronine
Transthyretin (prealbumin) Thyroxine, some steroids
Hormone Action

• Hormones alter target cell activity by one of the following


mechanisms:
• Ion Channel–Linked Receptors.
• G Protein–Linked Hormone Receptors.
• Enzyme-Linked Hormone Receptors.
• Intracellular Hormone Receptors and Activation of
Genes (steroid and thyroid hormones)
Hormone Action

• Hormones circulate to all tissues but only activate cells referred


to as target cells

• Target cells must have specific receptors to which the


hormone binds
Location of receptors:

• 1. In or on the surface of the cell membrane. The membrane


receptors are specific mostly for the protein, peptide, and
catecholamine hormones.

• 2. In the cell cytoplasm. The primary receptors for the different


steroid hormones are found mainly in the cytoplasm.

• 3. In the cell nucleus. The receptors for the thyroid hormones


are found in the nucleus and are believed to be located in direct
association with one or more of the chromosomes.
Steroid and Thyroid Hormones
(Genomic action)
• Steroid hormones and thyroid hormone diffuse easily into their
target cells
• Once inside, they bind and activate a specific intracellular receptor
• The hormone-receptor complex travels to the nucleus and binds a
DNA-associated receptor protein
• This interaction prompts DNA transcription to produce mRNA
• The mRNA is translated into proteins, which bring about a cellular
effect
Steroid & Thyroid Hormones - Mechanism of Action(Genomic Action)
Cyclic Adenosine Monophosphate (cAMP) Second Messenger
Mechanism(Non genomic action)
Hormone (first messenger) binds to its receptor, which then binds to
a G protein

The G protein is then activated as it binds GTP, displacing GDP

Activated G protein activates the effector enzyme adenylate cyclase

Adenylate cyclase generates cAMP (second messenger) from ATP


cAMP activates protein kinases, which then cause cellular effects
Cell Membrane Phospholipid: Second Messenger System
(Non genomic action)
Hormone binds to the receptor and activates
G protein

G protein binds and activates a phospholipase enzyme

Phospholipase splits the phospholipid PIP2 into diacylglycerol


(DAG) and IP3 (both act as second messengers)

DAG activates protein kinases; IP3 triggers release of Ca2+ stores


Ca2+ (third messenger) alters cellular responses
The Insulin Receptor & Mechanisms of Insulin Action
(Non genomic action)
Target Cell Activation

• Target cell activation depends on three factors


• Blood levels of the hormone
• Relative number of receptors on the target cell
• The affinity of those receptors for the hormone

• Up-regulation – target cells form more receptors in response to


the hormone

• Down-regulation – target cells lose receptors in response to the


hormone
Hormone Concentrations in the Blood

• Hormones circulate in the blood in two forms –


free or bound
• Steroids and thyroid hormone are attached to plasma
proteins
Hormone Concentrations in the Blood

• Concentrations of circulating hormone reflect:


• Rate of release
• Speed of inactivation and removal from the body
• Hormones are removed from the blood by:
• Degrading enzymes
• The kidneys
• Liver enzyme systems
EDOCRINE SYSTEM
HYPOTHALAMUS
• ‘Master Gland’
• Function : Control centre
• Attached to roof of third
ventricle, near thalamus
• Continuously receive
information on status of body
systems via nerve impulses
• Monitors composition &
temperature of blood
• Messages interpreted, evaluated
: outgoing messages dispatched
via nerves / hormones
• Plays role in feedback systems
that govern secretions of
endocrine system

Endocrine System…. Professor KS Satyapal 4


2. PITUITARY GLAND
• Pea sized mass of glandular
tissue
• Lies in sella turcica
• Slender stalk: Infundibulum
connects pituitary gland to
hypothalamus
• 2 parts : Neurohypophysis
Adenohypophysis
Indirectly controls :
• Growth
• Metabolism
• Sexual reproduction
• Lactation

Endocrine System…. Professor KS Satyapal 5


2. PITUITARY GLAND: PARTS
Neurohypophysis Adenohypophysis
Small posterior lobe Large anterior lobe
Stores hormones Releases hormones
Oxytocin Growth hormone (GH)
Anti Diuretic hormone Thyroid Stimulating hormone
(ADH) (TSH)
Adenocorticotropic hormone
(ACTH)
Lutenizing hormone (LH)

Follicle stimulating hormone


(FSH)
Melanocyte stimulating
hormone (MSH)
Prolactin (PRL)

Endocrine System…. Professor KS Satyapal


2. PITUITARY GLAND: HORMONES

HORMONES EFFECTS
Posterior Oxytocin (OC) Stimulates contraction of uterus & contractile
Pituitary cells of breast
ADH Prevents excess urine production
GH General body growth
ACTH Stimulate adrenal cortex to release hormone
TSH Controls thyroid gland
Anterior
Pituitary LH Stimulates sexual & reproductive function
FSH Stimulate production of sperm & egg in
ovaries & testis
MSH Related to skin pigmentation
PRL Initiates milk production in breast

Endocrine System…. Professor KS Satyapal


3. THYROID GLAND
• Located in middle anterior
part of neck: below larynx, in
front of trachea
• “Butterfly” shape
• 2 lobes connected by isthmus

• ↑ in size : puberty &


pregnancy
• Rich blood supply: able to
deliver high levels of
hormones in short period of
time
• Produces Thyroxin (T4) &
Tri-iodothyronine (T3)
• Calcitonin : involved in
calcium & phosphate
homeostasis
Endocrine System…. Professor KS Satyapal
4. PARATHYROID GLAND

• Small rounded mass


• Attached to posterior surface of
thyroid gland
• Produces Parathyroid hormone
(PTH)
• Controls homeostasis of calcium
& phosphate in blood by
activating Vitamin D

Endocrine System…. Professor KS Satyapal


5. THYMUS

• Plays a role in the immune


system

• Produces thymosin, thymic


humaral factor & thymic factor

• Responsible for maturation of


T-lymphocytes

Endocrine System…. Professor KS Satyapal


HARMONES OF THYROID, PARATHYROID & THYMUS

ORGAN HORMONE EFFECT


Thyroid gland T3 & T4 energy utilization
(Follicular cells)
 oxygen consumption
growth & development
Thyroid gland Calcitonin  Calcium ion concentration
(C cells) in body fluids
Parathyroid PTH  Calcium ion concentration
in body fluids
Thymus Thymosin Maturation & functional
competence of immune
system

Endocrine System…. Professor KS Satyapal


6. ADRENAL GLAND

• Located superior to the


kidney

• Divided into: (i) outer cortex


(ii) inner
medulla

Endocrine System…. Professor KS Satyapal


6. ADRENAL GLAND

ADRENAL CORTEX ADRENAL MEDULLA


Secretes steroid hormones Secretes hormones
controlled by ANS

Glucocorticoids Epinephrine (Adrenaline)


(metabolism) eg. cortisol
Mineralocorticoids Norepinephrine
(homeostasis of ions) eg. (Noradrenaline)
Aldosterone

Gonadocorticoids
(oestrogens & androgens)

Endocrine System…. Professor KS Satyapal


ADRENAL HORMONES
REGION HARMONES EFFECT
Cortex Mineralocorticoid: ­ Renal reabsorption of sodium ions
1. Zona glomerulos Aldosterone & water.
­ renal potassium ion loss
2. Zona fasciculata Glucocorticoid: Releases amino acids from skeletal
cortisol muscle & lipids from adipose.
Promotes liver glycogen & glucose
formation
Anti inflammatory effect

3. Zona Reticularis Androgens

Medulla Epinephrine cardiac activity


(Adrenaline), blood pressure
Norepinephrine glycogen breakdown
(Noradrenaline)
blood glucose

Endocrine System…. Professor KS Satyapal


7. PANCREAS
• Flattened organ
• Lies retroperitoneally &
transversly across posterior
abdominal wall
• Posterior to stomach, between
doudenum on right & spleen on
left
• Classified as exocrine &
endocrine
Hormones:
• Islets of Langerhans secrete:
Glucagon,  cells :  blood
glucose
Insulin,  cells:  blood glucose
• Growth harmone inhibiting
hormone (GHIH),  cells :
inhibits glucagon & insulin

Endocrine System…. Professor KS Satyapal


HORMONES OF PANCREAS

CELLS HARMONE EFFECT

Alpha () cells Glucagon Glucose synthesis & glycogen


breakdown in liver
 Blood glucose concentration
Beta () cells Insulin Stimulation of lipids & glycogen
storage & formation
 Blood glucose concentration
Delta () cells Somatostatin Inhibits secretion of insulin &
glucagon

Endocrine System…. Professor KS Satyapal


12 & 13. TESTES & OVARIES
TESTES:
• Located within scrotum
• Produce testosterone
• Stimulates development of male
sexual characteristics

OVARIES:
• Located in pelvic cavity
• Produce oestrogen &
progesterone
• Responsible for development &
maintenance of female
characteristics & menstrual cycle

Endocrine System…. Professor KS Satyapal


HORMONES OF REPRODUCTIVE SYSTEM

CELLS HORMONES EFFECT


Testes 1. Testosterone 1. Maturation of sperm
Interstitial cells 2. Inhibin Male secondary sex characteristics
2. Inhibits secretion of FSH
Ovaries 1. Oestrogen 1. Follicle maturation
Follicle cells 2. Inhibin Female secondary sex characteristic
2. Inhibits secretion of FSH
Corpus Luteum Progesterone Prepare uterus for implantation
Prepare breast for secretory function

Endocrine System…. Professor KS Satyapal


OTHER ENDOCRINE TISSUES
KIDNEYS:
• Renal Erythropoietic factor: erythropoietin

HEART:
• Atrial Natriuretic factor (ANF)

GIT:
• Stomach gastrin, enteric gastrin, secretin, cholecystokinin,
enterocinin, gastric inhibiting hormone

PLACENTA:
• Human chorionic gonadotropin, oestrogen, progesterone,
relaxin

Endocrine System…. Professor KS Satyapal


Thanks

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