Endocrine System

CARINA C. GOMEZ, M.D. F.P.S.P.

Department of Physiology
Introduction to
Endocrinology
 ENDOCRINE SYSTEM
■ collection of glands whose
function is to regulate
multiple organs within the
body to;
■ synthesize and secrete
biologic hormones

Taken from: humananatomybody.info

 Chapter 37 Introduction

Dedicated Endocrine Glands

● Table 37-1.
Hormones and Their Sites of Production in
Nonpregnant Adults
Gland Hormone
Hormones Synthesized and Secreted by Dedicated Endocrine
Glands
Growth hormone (GH)
Prolactin
Adrenocorticotropic hormone (ACTH)
Pituitary gland
Organs whose function is Thyroid-stimulating hormone (TSH)
Follicle-stimulating hormone (FSH)
only endocrine except Luteinizing hormone (LH)
Tetraiodothyronine (T4; thyroxine)
gonads (perform exocrine Thyroid gland Triiodothyronine (T3)
Calcitonin
function) — Parathyroid glands Parathyroid hormone (PTH)
Insulin
Islets of Langerhans
gametogenesis (endocrine pancreas)
Glucagon
Somatostatin
Epinephrine
Norepinephrine
Adrenal gland Cortisol
Aldosterone
Dehydroepiandrosterone sulfate (DHEAS)
Estradiol-17β
Ovaries Progesterone
Inhibin
Testosterone
Testes Antimüllerian hormone (AMH)
Inhibin
Hormones Synthesized in Organs with a Primary Function Other
Taken from: Berne and Levy, Medical Physiology, updated edition
Than Endocrine
 Somatostatin
Epinephrine
Norepinephrine
Adrenal gland Cortisol
Aldosterone
Dehydroepiandrosterone sulfate (DHEAS)
Estradiol-17β

Organs with Endocrine Functions

Ovaries Progesterone
Inhibin
Testosterone
Testes Antimüllerian hormone (AMH)
Inhibin
■ organs than contain Hormones Synthesized in Organs with a Primary Function Other
Than Endocrine

endocrine cells whose Antidiuretic hormone (ADH; vasopressin)

Oxytocin
Corticotropin-releasing hormone (CRH)

primary function is not Brain (hypothalamus)

Thyrotropin-releasing hormone (TRH)
Gonadotropin-releasing hormone (GnRH)
Growth hormone–releasing hormone (GHRH)
endocrine Somatostatin
Dopamine
Brain (pineal gland) Melatonin
■ Examples Heart
Kidney
Atrial natriuretic peptide (ANP)
Erythropoietin
Leptin
■ Heart Adipose tissue
Adiponectin
Gastrin
■ Kidney Stomach Somatostatin
Ghrelin
Secretin
■ Liver Cholecystokinin
Glucagon-like peptide-1 (GLP-1)
Intestines Glucagon-like peptide-2 (GLP-2)
■ Gastrointestinal tract Glucose-dependent insulinotropic peptide
(GIP; gastrin inhibitory peptide)
Motilin
■ Some parts of the brain Liver Insulin-like growth factor type I (IGF-I)
Taken from: Produced
Hormones Berne andto
Levy, Medical
a SignificantPhysiology,
Degree byupdated edition
Peripheral
 Adipose tissue
Adiponectin
Gastrin
Stomach Somatostatin
Ghrelin
Secretin
Cholecystokinin

Organs with Specific Cells

Intestines
Glucagon-like peptide-1 (GLP-1)
Glucagon-like peptide-2 (GLP-2)
Glucose-dependent insulinotropic peptid
(GIP; gastrin inhibitory peptide)
Motilin
■ Express intracellular Liver Insulin-like growth factor type I (IGF-I)
Hormones Produced to a Significant Degree by Peripheral
enzymes, ecto- Conversion
Lungs Angiotensin II
enzymes or secreted Kidney 1,25-Dihydroxyvitamin D (vitamin D)
Adipose, mammary glands,
enzymes that modify other organs
Estradiol-17β
Liver, sebaceous gland,
inactive precursors other organs
Testosterone
Genital skin, prostate,
or less active other organs
Many organs
5-Dihydrotestosterone (DHT)
T3
hormones into highly Taken from: Berne and Levy, Medical Physiology, updated edition

active hormones
■ Angiotensin II
■ 1,25 (OH)2D3
 HORMONES
■ from Greek word “
horman” meaning to set
in motion
■ mediators that control Taken from: www.dreamstime.com

mechanism in endocrine
system
■ classes of hormones
■ Protein (100 amino acids) and
Polypeptide Hormones
■ Steroid Hormones
■ Amine Hormones
Taken from: plus.google.com
 PROTEIN / STEROID
HORMONES AMINES
POLYPEPTIDE

smooth ER variable site

SYNTHESIS rough ER amino acids
(cholesterol)
(aromatic)
Hydrophilic (polar)
hydrophobic (lipophilic) hydrophilic
PROPERTY (impermeable)
(permeable) impermeable

Storage and release Synthesis Storage and release

REGULATION (regulatory) (constitutive) (regulatory)

protein bound
non protein bound (free) protein bound
(thyroid hromone)
TRANSPORT dissolved in plasma (t1/2 free form
free form
short) (longer halflife)
catecholamines

STORED yes no yes\no

RELEASE exocytosis diffusion exocytosis

EXCRETION kidney and liver liver (bile) kidney and liver

 PROTEIN /
HORMONES STEROID AMINES
POLYPEPTIDE
Cell membrane
Cytoplasmic
RECEPTOR (catecholamine)
Cell membrane Nuclear
LOCATION Nuclear
(channels and enzyme) (gene transcription)
(thyroid
hormone)
rapid
(catecholamines)
DEGRADA- rapid
slow slow
TION (enzyme)
(thyroid
hormones)
hypothalamus (CRH, adrenal cortex (cortisol,
TRH, GnRH, PRH, aldosterone and androgen
GHRH, ADH and DHT)
oxytocin) ovary (estrogen and catecholamines
pituitary gland (FSH, LH, progesterone) thyroid hormones
EXAMPLES TSH, ACTH, GH and testes (estrogen and serotonin
prolactin testosterone)
pancreatic islets (glucagon, placenta (estrogen and
insulin, somatostatin) progesterone)
parathyroid (PTH) 1,25 (OH)2D3 and retinol
 Regulation of Hormone Secretion
■ Negative Feedback Endocrine axis driven Physiological response
Mechanism feedback loop driven feedback loop

■ prevents overactivity

of hormone ↓ blood calcium

(stimulus)
■ ensure a proper level

of hormone activity at
the target tissue ↑ PTH secretion

■ Two basic configurations

■ Physiological response
driven feedback loop ↑ calcium level
■ Endocrine axis driven
feedback loop.
 Regulation of Hormone Secretion
■ Positive Feedback
Mechanism ↑ estrogen
■ prevents overactivity of
hormone
(+) pituitary gland
■ Example
■ secretion of LH

before ovulation
↑ LH (surge
due to stimulatory
effect of estrogen
■ secretion of

oxytocin during
parturition
Regulation of Hormone Secretion
■ Direct Neural Control
■ secretion of catecholamine frrom adrenal medulla
■ Chronotropic Control
■ Oscillating
■ Pulsatile
■ Diurnal Rhythm
■ Sleep-wake cycle
■ Menstrual Rhythm
■ Seasonal rhythm
■ Developmental Rhythm
 Mechanism of Action
■ First Step
■ Binding of hormone to specific receptors
■ Receptors
■ usually are large proteins (2000 to 100,000 each cell)
■ highly specific
■ can undergo up or down regulation
■ location:

Peptides, Proteins and Catecholamines

- cell membrane
Steroid Hormones
- cytoplasm
Thyroid Hormones
- nuclear
 Mechanism of Action
■ Second Step
■ formation of
hormone-receptor
complex
■ alters the function of
the receptor which
initiates or blocks
the hormonal
effects.

Taken from: Berne and Levy, Medical Physiology, Updated edition

 Mechanism of Action
■ Third Step
■ Some hormones change the membrane permeability
■ by opening or closing ion channels (Epinephrine and
Norepinephrine)
■ Some hormones activate or inactivate intracellular
enzymes.
■ a portion of the receptor protrudes outside and inside the
cell (insulin)
■ Some forms second messengers
■ Some hormones activate genes
■ activate specific portion of the DNA → RNA→ proteins
(thyroid hormones)
Anterior Pituitary
 Rathke’s pouch Neural tissue
Epithelioid cell type Glial cell type
Portal hypophysial vessels Neural connection
Hormone secretion Neurohormone secretion
 Anterior Pituitary Gland
■ a.k.a. Adenohypophysis
■ three parts
■ pars distalis
■ major part (90%)
■ “anterior pituitary gland”
■ pars tuberalis
■ wraps around the stalk
■ pars tuberalis and
infundibulum from
pituitary stalk”
■ pars intermedia
■ regresses and becomes
rudimentary in adult
Different Cell Types (anterior pituitary)
% OF TOTAL
CELL TYPE HORMONE SECRETED SECRETORY CELLS STAIN AFFINITY

Somatotrope Growth hormone (GH) 50 Acidophilic

Lactotrope/ Prolactin (PRL) 10 - 30

mammotrope Acidophilic

Corticotrope ACTH, β-LPH 10 - 20 Basophilic

POMC cells
Thyrotrope TSH 5 Basophilic

Gonadotrope FSH, LH 15 - 20 Basophilic

Growth hormone, Prolactin and ACTH - Simple polypeptides/proteins

TSH, LH and FSH - glycoproteins α and β subunits (hCG)

Taken from: Berne and Levy, Medical Physiology, updated edition
 Growth Hormone (GH)
■ a.k.a. Somatotropin (STH)
■ small protein (191 a.a)
■ exert its effects directly on all
or almost all tissues of the
body (not on target glands).
■ secreted in a pulsatile pattern
■ secretion decreases slowly
with aging (25% at very old
age)

Taken from: Berne and Levy, Medical Physiology, updated edition

Ventromedial nuclues

Regulation - Negative Feedback

dominant
The major long term controller of
adenylate cyclase
cAMP GH secretion —- long term state
of nutrition (protein level)
—
 Figure 75-6 Typical variations in growth hormone secretion throughout the day, demonstrating the
Regulation of Growth Hormone Seretion
especially powerful effect of strenuous exercise and also the high rate of growth hormone secretion
that occurs during the first few hours of deep sleep.

Table 75-3. Factors That Stimulate or Inhibit Secretion of Growth Hormone

Stimulate Growth Hormone
Secretion Inhibit Growth Hormone Secretion
Decreased blood glucose Increased blood glucose
Decreased blood free fatty acids Increased blood free fatty acids
Increased blood amino acids (arginine) Aging
Starvation or fasting, protein deficiency Obesity
Trauma, stress, excitement Growth hormone inhibitory hormone
Exercise (somatostatin)
Testosterone, estrogen Growth hormone (exogenous)
Deep sleep (stages II and IV) Somatomedins (insulin-like growth factors)
Growth hormone-releasing hormone Cortisol, REM sleep
Ghrelin
he Taken from: Guyton and Hall. Medical Physiology, 12 edition
normal concentration of growth hormone in the plasma of an adult is between 1.6 and 3 ng/ml; in
ild or adolescent, it is about 6 ng/ml. These values often increase to as high as 50 ng/ml after
epletion of the body stores of proteins or carbohydrates during prolonged starvation.
nder acute conditions, hypoglycemia is a far more potent stimulator of growth hormone secretion th
Guyton & Hall: Textbook of Medical Physiology, 12e [Vishal] Physiological Functions of Growth Hormone

Adult - 1.6 – 3 ng/ml

Child/adolescence - 6 ng/ml
Prolonged Starvation - 50 ng/ml
(Depletion of CHO and CHON
stores)

Figure 75-6 Typical variations in growth hormone secretion throughout the day, demonstrating the
especially powerful effect of strenuous exercise and also the high rate of growth hormone secretion
that occurs during the first few hours of deep sleep.

Table 75-3. Factors That Stimulate or Inhibit Secretion of Growth Hormone

Taken from: Guyton and Hall. Medical Physiology, 12 edition
Stimulate Growth Hormone !25
Secretion Inhibit Growth Hormone Secretion
Biologic Effects
■ Direct effect (metabolic)
■ stimulates the

secretion
somatomedins C
■ Indirect (growth)
■ through intermediary

substance (IGF 1 and

IGF II)
Somatomedins or IGF
■ intermediate substances through which growth hormone
exerts much of its effects.
■ has long duration of action than growth hormone
■ deficiency
■ “Pygmies of Africa

■ Levi Lorain Dwarf

IGF – I (SOMATOMEDIN C)
- most important
IGF – II
Metabolic Effects
■ ↑ rate of protein synthesis in most cells (begin in
minutes)
■ ↑ mobilization of fatty acids from adipose tissue
(begin several hours)
■ used for energy (spare CHON and CHO)
■ ketogenic effect (ketosis) - cause fatty liver
■ ↓ rate of glucose utilization throughout the body.
(↑ production of glucose in the liver and ↑ insulin
secretion)
■ diabetogenic effect (diabetes)
■ growth hormone -induced insulin resistance
Abnormalities of Growth Hormone
Secretion
■ Dwarfism
■ mostly result from
panhypopituitarism during
childhood (no sexual maturation)
■ Adult – panhypopituitarism
(craniopharyngioma and
chromophobe tumors, tumor
thrombosis
■ can be due to GH or
somatomedin C deficiency.
■ decreased rate of development
Abnormalities of Growth Hormone
Secretion
■ Dwarfism
■ Treatment
■ growth hormone from E coli
by DNA technology
■ A child who has reached
■ age of 10 years may have the
bodily development of a child
aged 4 to 5 years,
■ same person at age 20 years
may have the bodily
development of a child aged 7
to 10 years.
■
Abnormalities of Growth Hormone
Secretion
■ Gigantism
■ due to excessive production
of growth hormone before
puberty.
■ all body tissues grow
rapidly including the bones.
■ accompanied by
hyperglycemia, ketosis and
degeneration of Beta cells
■ usually caused by a tumor.
Abnormalities of Growth Hormone
Secretion
■ Acromegaly
■ due to excessive production
of growth hormone after
puberty.
■ soft tissues grow but not
the bones (except
membranous bones).
■ accompanied by
hyperglycemia, ketosis and
degeneration of Beta cells
■ usually caused by a tumor.
Prolactin (PRL)
■ structurally related to growth hormone and
human placental lactogen (hPL)
■ responsible for lactogenesis
■ characteristics
■ not part of endocrine axis (directly act on
neuroendocrine cells)
■ production is under inhibitory control of

hypothalamus (resection of pituitary stalk) -

increases prolactin)
Prolactin (PRL)
■ its receptor is a member of cytokine family
coupled to JAK/STAT signalling pathway.
■ cause breast development (estrogen and
progesterone.)
■ stimulates milk production/secretion.
■ stimulates maternal behavior.
■ influences reproductive function and immune
responses.
■ (-) ovulation by decreasing GNRH
 Estrogen,TRH, secretin, glucagon,
GIP, stress, breast feeding and sleep
Somatostatin, TSH,
GH, Somatostatin
and dopamine agonist

Dopamine antagonist

increases Prolactin
 Thyroid Stimulating Hormone (TSH)
■ also known as thyrotropin
■ (+) every aspect of thyroid
function
■ Functions
■ Immediate
■ Intermediate
■ Long term

Taken from: www.antiagingpittsburgh.com

 Thyroid Stimulating Hormone (TSH)
■ Immediate
■ ! activity of the iodide
pump
■ ! TPO activity
■ ! iodination of tyrosine
■ induction of pseudopod
extension
■ endocytosis of colloid
■ formation of colloid
droplets in the cytoplasm
■ ! proteolysis of the
thyroglobulin
Taken from: Berne and Levy, Medical Physiology, updated edition
 Thyroid Stimulating Hormone (TSH)
■ Functions
■ Intermediate
■ Protein synthesis
■ Expression of
numerous genes
■ Megalin

■ TPO

■ Thyroglobulin

■ NIS

Taken from: Berne and Levy, Medical Physiology, updated edition

 Thyroid Stimulating Hormone (TSH)
■ Functions
■ Long term
■ ! size and secretory activity of the thyroid cells
■ ! number of thyroid cells
■ ! capillary proliferation and blood flow

Taken from: ntp.niehs.nih.gov Taken from: www.slideshare.net

Follicle Stimulating Hormone (FSH)

■ Stimulates the ovarian follicle growth.

■ (+) granulaosa cells —- estrogen and inhibin

■ Stimulates spermatogenesis.
■ (+) sertoli cells - estrogen, AMH, inhibin
and ABP.
Leutenizing Hormone (LH)
■ Stimulates ovulation and
leuteinization of ovarian follicles.
■ (+) theca cells - progesterone
■ (+) leydig cells — testosterone
secretion.
ADRENOCORTICOTROPIN (ACTH)
 PROOPIOMELANOCORTIN (POMC)

Opioids Peptides
ANTERIOR PITUITARY
INTERMEDIATE LOBE (cortocitropes) ENDORPHINS

Intermediate lobe-cells ENKEPHALINS

Hypothalamus
Lungs
GIT
placenta
Posterior Pituitary
 Posterior Pituitary
❖ Neurohypophysis
❖ Median eminence
❖ Infundibulum
❖ Pars Nervosa
❖ outgrowth of hypothalamus
❖ neural type of cell
❖ has neurovascular connection with
hypothalamus
❖ cell bodies that project to Pars Nervosa
❖ Are located in the
❖ Supraoptic nucleus (SON)
❖ Paraventricular nucleus (PVN)
❖ peptide hormones released
(nonapeptide hormones)
❖ ADH (antidiuretic hormone/
arginine vasopressin)
❖ OXYTOCIN
Taken from: Berne and Levy. Medical Physiology, 6th updated edition
 ADH
■ a.k.a. antidiuretic hormone or arginine
vasopressin
■ Biosynthesis : Hypothalamus (Supraoptic
and Paraventricular nuclei)
■ Receptors : Osmoreceptors (responds to
effective osmoles)
■ Storage and Release : Posterior Pituitary
Gland
Stimuli Affecting Vasopressin Secretion
VASOPRESSIN SECRETION VASOPRESSIN SECRETION
INCREASED DECREASED

Increased extracellular Decreased extracellular fluid

osmolarity (osmotic) osmolarity

Decreased extracellular fluid Increased extracellular fluid

volume and arterial blood volume
pressure (hemodynamic)

Pain, emotion, stress , exercise Alcohol

and standing

Nausea and vomiting Atrial Natriuretic Peptide

Angiotensin II, Carbamazepine

And nicotine
Increased ECF osmolarity (1%) - - thirst center 2 to 3%
 Biologic Effects
■ regulate volume and
osmolarity of urine and
ECF.
■ increases water
permeability in the
collecting duct and
medullary collecting duct AQP3
AQP4
to urea.
UT-A1

■ causes vasoconstriction UT-A3

(V1A) receptor - large

quantities
 ADH ACTION ON THE KIDNEY

■ increases water permeability

■ collecting duct
■ increases urea permeability
■ medullary collecting duct
■ stimulates reabsorption of NaCl
■ thick ascending loop of Henle
(NKCC2 or 1Na+ 1K+ 2Cl-)
■ distal tubule (NCC or Na+Cl- )
■ distal tubule and cortical collecting
duct (eNAC)
■ causes vasoconstriction (V1A)
receptor - large quantities
Types of Vasopressin Receptor
■ VIA receptor
■ mediates vasoconstrictor effect
■ glycogenolysis (liver)
■ VIB receptor
■ mediates increased ACTH secretion in the anterior
pituitary gland.
■ V2 receptor
■ mediates antidiuretic effect
Types of Aquaporins (AQP)
■ Aquaporin I (Kidney)
■ Aquaporin 2 (Kidney)
■ Vasopressin-Responsive Water Channel
■ Aquaporin 3 (Kidney)
■ Aquaporin 4 (Brain)
■ Aquaporin 5 (Salivary Glands, Lacrimal
Glands and Respiratory Tract)
 CLINICAL IMPLICATION

DIABETES INSIPIDUS
Neurogenic Diabetes Insipidus
■ a.k.a. pituitary diabetes insipidus
■ inadequate release of ADH (ADH
deficiency)
■ ADH level is low
■ can be inherited and commonly
caused by brain neoplasms (30%),
head trauma (30%), idiopathic
(30%) infection, vascular lesions
and others
■ treatment is administration of
exogenous ADH
■ polyuria and polydipsia
Nephrogenic Diabetes Insipidus
■ diabetes insipidus with primary defect
in the kidney
■ inability of the kidney to respond to
ADH
■ ADH level is normal or high
■ congenital defect in V2 receptor (X-
linked, 90%) or non functional AQP2
(10%), drugs (lithium), ureteral
obstruction, low protein diet and
hypercalcemia
■ Polyuria and polydipsia
SIADH
■ Syndrome of Inappropriate Hypersecretion of Antidiuretic
Hormone
■ high plasma level of ADH above what would be expected on
the basis of body fluid osmolality and blood volume and
pressure.
■ water is retained hence produce concentrated urine
■ result to body fluid hypoosmolality (dilutional hyponatremia)
■ can be due to brain neoplasm and infection, drugs, cerebral
disease (cerebral salt wasting) and pulmonary disease
(pulmonary salt wasting)
Oxytocin
■ secretion is stimulated by suckling,
dilatation of the cervix and orgasm
■ causes contraction of;
■ smooth muscle of the uterus
■ initiates labor
■ causes birth of the baby
■ reduce post partum bleeding
■ smooth muscle of the breast
■ stimulates milk letdown or ejection
Thyroid Gland
 PYRAMIDAL LOBE

LEFT LOBE RIGHT LOBE

ISTHMUS
THYROID FOLLICLES (ACINI) - FUNCTIONAL UNIT

200 – 300 µm
THYROID FOLLICLES

FOLLICULAR CELLS

COLLOID

PARAFOLLICULAR CELLS
 Thyroid Hormone Synthesis and
Secretion
■ IODIDE TRAPPING
■ OXIDATION OF
IODIDE IONS
■ IODINATION OF
TYROSINE
MOLECULES
■ COUPLING
REACTION TWO PRECURSORS
IODINE
THYROGLOBULIN
 Functions
■ stimulates O2 consumptions of most of the
cells in the body.
■ helps regulate lipid and CHO metabolism.
■ necessary for normal growth and maturation.
■ conversion of beta carotine to vitamin A
 Physiology Effects
■ Increase oxygen consumption
■ Increase cellular rate of metabolism (UCPs)
■ Decrease body weight
■ Increases heat production (thermogenesis)
■ Increases heat loss
■ Increase activity of;
■ CVS
■ Respiratory
■ Renal
■ GIT
■ CNS
 PHYSIOLOGIC EFFECTS
■ Growth and maturation
■ Bone, Hard tissue and Dermis
■ Promote bone development
■ Progression of tooth development and eruption
■ Promote normal cycle of growth and maturation of
epidermis (hair follicles and nails) and its degradative
process.
■ Inhibits the synthesis and increasing the degradation of
mucopolysaccharidesand fibronectin in extracellular
connective tissue
DISORDERS
■ HYPERTHYROIDISM

■ HYPOTHYROIDISM

■ GOITER
HYPERTHYRODISM
■ enlargement of thyroid gland (most cases)
■ excessive TSH
■ immunoglobulin antibodies (TSI) - autoimmunity
■ hyperplasia and infolding of follicular cell
lining
■ increased thyroid hormone secretion
HYPERTHYRODISM
■ Primary Hyperthyroidism
■ Grave’s disease (most common form -- thyrotoxicosis )
↑ T3 and T4 ↓ TSH

■ Secondary Hyperthyroidism
■ secondary to an increase secretion of TSH (pituitary
hyperthyroidism) or TRH (hypothalamic
hyperthyroidism)
■ Causes
■ Pituitary and Hypothalamic tumor
↑ T3 and T4 ↑ TSH
 HYPERTHYRODISM
■ Manifestations
■ ↑ BMR
■ excessive weight loss and appetite
■ heat intolerance, excessive sweating, warm

and soft skin

■ increased water intake

■ ↑ adrenergic activity
■ tachycardia
■ palpitations
 Hyperthyroidism
■ Manifestations
■ Nervous system
■ hyperkinesis
■ nervousness, insomia and other psychic disorders
■ fine tremors
■ diarrhea
■ muscle weakness and fatigue
■ increased pulse pressure
■ exophthalmus
■ edematous swelling and degenerative changes
Adrenal Gland
Aorta, Renal arteries and phrenic arteries
 MINERALOCORTICOIDS
■ Aldosterone - principal mineralocorticoid
■ accounts for about 90%

■ 60% (protein-bound), 40% (free form)

■ halflife – 20 minutes

■ destroyed mainly in the liver (bile/feces, 25%), mainly

excreted in the urine

■ mainly affect electrolytes (minerals K+/Na+) of the ECF.
■ Deoxycorticosterone, Corticosterone,Cortisone, Cortisol and 9α
Fluorocortisol (synthetic)
↓ ABP
 Biologic Effects
■ ! renal tubular reabsorption of sodium (DCT
and CD)
■ ! renal tubular secretion of potassium (DCT and
CD)
■ ! renal tubular secretion of hydrogen (DCT and
CD)
■ maintenance of ECF volume (principal function)
■ same effect (sweat glands, salivary glands,
intestinal epithelial cells (colon)
■ Primary Aldosteronism (Conn’s Syndrome)
■ caused by a tumor of the zona glomerulosa cells or
hyperplasia of the adrenal cortices.
■ manifested by;
■ hypokalemia
■ ! ECFV (slight)
■ plasma Na+ concentration (very slight)
■ Hypertension
■ muscle weakness
 HYPERALDOSTERONISM
hypernatremia ! sodium reabsorption hypertension
hypokalemia ! potassium secretion ! ECFV

" ABP mild alkalosis ! hydrogen secretion ! ABP

" ECFV
" RBF ALDOSTERONE !total peripheral
! Sympathetic discharge
resistance
KIDNEY ADRENAL CORTEX

(+)
RENIN ACE (LUNGS) potent vasoconstrictor

ANGOITENSINOGEN ANGOITENSIN I ANGIOTENSIN II

■ ! aldosterone level " renin level

negative feedback

❑ Secondary Aldosteronism
- ! aldosterone level ! renin
level
tumor (kidney)
 GLUCOCORTICOIDS
■ Cortisol (hydrocortisone) – principal glucocorticoid
■ accounts for about 95% of all glucocorticoid activity
■ 90 - 95% (protein bound), 10 -15% (free form)
■ mainly to globulin (cortisol binding globulin or transcortin) and
albumin
■ halflife – 60 to 90 minutes
■ destroyed mainly in the liver (bile/feces, 25%), mainly
excreted in the urine
■ Corticosterone, Cortisone (synthetic), Prednisone
(synthetic), Methylprednisone (synthetic),
Dexamethasone (synthetic)
 Cortisol
■ glucocorticoid
■ increases blood glucose level
■ has slight mineralocorticoid activity
■ helps to resist physical, mental and other
types of stresses.
■ essential for life
BIOLOGIC EFFECTS
METABOLIC EFFECTS
■ Carbohydrates Metabolism (Diabetogenic Effect)
■ stimulates gluconeogenesis from CHON (liver)
■ main effect
■ decreases glucose utilization by cells
( anti insulin)
■ increases;
■ glucose-6-phosphatase
■ gluconeogenic enzymes
■ critical for the survival during fasting“
■ adrenal diabetes” and “! insulin secretion”
■ Protein Metabolism (Catabolic/Antianabolic)
■ ↑ protein catabolism and ↓ protein synthesis
■ facilitate conversion of protein to glucose
■ ↓ proteins in the body except liver and plasma
■ increases plasma and liver proteins
■ Fat Metabolism (Catabolic/Antianabolic)
■ (+) lipolysis (growth hormone and epinephrine)
- extremities
■ (+) lipogenesis (central portion of the body)
■ (+) ketogenesis
■ Permissive action
■
cortisol may amplify the effect of another
hormone on a process that it does not affect
directly.
■ potentiates and extends the action of glucagon,
epinephrine and growth hormone
Summary
■ Cortisol has; (when stimulated by stress)
■ Diabetogenic Effect (gluconeogenesis and anti-
insulin effect)
■ Lipolytic (extremities), Lipogenetic (central
body region) and Ketogenic Effect
■ Proteolytic Effect
 Cushing’s Syndrome
■ adrenal hypercorticolism
■ causes
■ exogenous corticosteriod
(most common)
■ ACTH secreting tumor
■ functional adrenal tumor
■ functional pituitary
adenoma (Cushing’s
Disease)
Taken from: www.oliveviewim.org
 Hyperadrenalism (Cushing’s
Syndrome)
■ caused by adrenal cortex adenoma, bilateral adrenal
cortex hyperplasia and administration of large amount of
cortisol ! cortisol " ACTH
■ manifested by;
■ Buffalo hump hypertension
■ Moon face hypernatremia
■ Truncal obesity (centripetal) hypokalemia
■ Purplish striae mild alkalosis
■ Weakness vertebral fractures
■ Osteoporosis easy bruisability
■ Diabetes psychiatric disorders
■ Secondary Hypercorticolism
■ pituitary adenoma
■ abnormal function of hypothalamus
■ ectopic secretion of ACTH

! cortisol ! ACTH
 Addison’s Disease
■ a primary adrenal
insufficiency
■ causes
■ atrophy of adrenal cortex
(autoimmune disease) Taken from: diseaselist.org

■ tuberculous destruction
■ cancer invasion (adrenal
cortex)
■ has both glucocorticoid and
mineralocorticoid deficiency

Taken from: www.slideshare.net

 Addison’s Disease
■ manifestations
■ skin pigmentation (high
ACTH) - MC1R
■ circulatory hypovolemia
( ECF volume)
Taken from: diseaselist.org

■ TPR
■ hypotension
■ weight loss ( appetite
and GI dysfunction)

Taken from: www.slideshare.net

 Addison’s Disease
■ manifestations
■ prone to hypoglycemia
■ inability to cope up stress
■ water intoxication
■ muscle weakness Taken from: diseaselist.org

■ anemia
■ GI motility and secretion
■ iron and vitamin B12
absorption
■ disturbances in mood and
behavior - Depression
Taken from: www.slideshare.net
 ANDROGENS
■ Dehydroipeandrosterone (DHEA) and
androstenedione
■ principal cortical androgens
■ responsible for the early development of male sex
organs.
■ converted to testosterone (potent)
■ “musculinizing effect”
■ also secrete estrogen (estradiol) and progesterone
 Androgenital Syndrome
■ develops intense musculinizing effects throughout
the body (virilism)
■ Growth of beard
■ Deeper voice
■ Baldness
■ Musculine hair distribution
■ Growth of clitoris
■ Loss of regular of menses
■ Regression of breast tissue
ADRENAL MEDULLA CHROMAFFIN CELLS
(Neural crest-derived cells)

MIGRATE

ADRENAL CORTEX

BECOME

ENCAPSULATED BY
CORTICAL CELLS

FORMING

ADRENAL MEDULLA
NEUROECTODERMAL (Chromaffin cells)
TISSUE (10 – 20 %)

DEVELOP

CATECHOLAMINES
Epinephrine POSTGANGLIONIC
Norepinephrine SYMPATHETIC NEURONS
 ADRENAL MEDULLA
■ sympathetic ganglion in which the
postganglionic neurons have lost their axons
and become secretory cells.
■ two types of cells
■ Epinephrine-secreting type (80-90%)
■ Norepinephrine-secreting type (10-20%)
■ secretes epinephrine (80-90%),
norepinephrine (10-20%) and dopamine
■ 95% dopamine, 70% epinephrine and
norepinephrine are conjugated to sulfate.
■ halflife is 2 minutes in the circulation
■ excreted in the urine, 50% as free and
conjugated metanephrine and
normetanephrine, 35% VMA and small
amount of free E and NE.
 DEGRADATION
OF
CATECHOLAMINES
 E / NE
CATECHOLAMINES
Epinephrine and norepinephrine
are potent agonists for Circulation
α1 and α2 receptors
β1 and β3 receptors α1, α1, β1, β2, β3
β2 - E > NE

α - NE > E increase sympathetic

response
β - E > NE
PHYSIOLOGICAL DIFFERENCES
PARAMETERS NE E

CO +++ ++++
ABP ++++ ++++
(+)CNS ++++ ++++
Hyperglycemia + ++++
Gonads
 Female Monthly
Sexual Cycle

Average – 28 days
short – 20 days
long – 45 days
Ovarian Cycle

Reproductive years
13 – 46 years

Uterine Cycle
UTERINE CYCLE
LH secretion - high frequency FSH secretion - low frequency
GnRH pulses GnRH pulses

CHILDHOOD – no FSH/LH
9 to 12 y/o – begins to secrete
FSH/LH

(-) PUBERTY

(-) (-)

inhibin MENARCHE
(11 – 15 y/o)
Pancreatic Islets
 Pancreatic Islets Cells
■ A cell (α cell) - glucagon (catabolic hormone)
■ B cell (β cell) - insulin (anabolic hormone)
■ D cell (δ cell) - somatostatin (regulatory hormone)
■ F cell (PP cell) - pancreatic polypeptide
 INSULIN
packed and secreted along
■ a polypeptide with two with insulin (concentration used to
straight peptide chains that monitor beta cell function

are linked together by

disulfide linkages.
■ A chain - 21 amino acids
■ B chain - 30 amino acids
■ belongs to gene family that
includes IGF I and II
■ synthesized as preproinsulin
—- proinsulin —- insulin Taken from: www.diapedia.org
 INSULIN
■ an anabolic hormone that
maintains upper limit of
blood glucose and FFA
level
■ half life is 5 – 8 minutes
■ degraded by insulinase in
the liver, kidney and other
tissues.
Taken from: www.diapedia.org
 INSULIN
■ serum levels normally
begin to rise within 10
minutes after ingestion of
food and reach a peak in
30 – 45 minutes.
■ primary stimulus is
glucose (hyperglycemia)
■ promotes hypoglycemia
 Regulation of Insulin Secretion
Negative Feedback
(Physiological response
driven feedback loop)

↑ blood glucose level

(stimulus)

↑ insulin secretion

↓ glucose level
(response)
 Other excitatory stimuli:
■ GI hormones (GIP, Gastrin, Secretin, CCK, EGluc.)
■ Amino acids (arginine, leucine, lysine)
■ Medium-chain triglycerides
■ β-adrenergic stimulators
■ β-keto acids
■ Glucagon
■ Acetylcholine
■ cAMP and cAMP generating agents
■ STH
■ Cortisol
Inhibitory stimuli:
■ Somatostatin
■ Galanin
■ Potassium depletion
■ Hypoglycemia
■ β-adrenergic blockers
■ α-adrenergic stimulators
■ Insulin
Insulin Receptor Activation (Tyrosine
kinase Receptor)

!123
 Principal Actions of Insulin
■ Rapid (seconds)
■ Increases transport of glucose, amino acids and K+ into insulin
sensitive cells by insertion of glucose transporters
■ Intermediate (minutes)
■ Promotes protein anabolism
■ Prevents protein catabolism
■ Promotes glycogenesis and (-) glycogenolysis
■ Decreases gluconeogenesis
■ Delayed (hours)
■ Promotes lipogenesis and (-) lipolysis
■ General
■ Increases cell growth
 Increases glucose uptake in:
■ Skeletal muscles
■ Cardiac muscles
mainly on these tissues
■ Smooth muscles
■ Adipose tissues
■ Leukocytes
■ Crystalline lens
■ Hypophysis
■ Fibroblasts
■ Mammary glands
■ A cells of the Islets
 Diabetes Mellitus
■ a metabolic disorder charac-
terized by hyperglycemia.
■ insulin levels or
responsiveness of tissue to
insulin (or both) is
insufficient to maintain
normal levels of plasma
glucose.
■ promotes imbalances in
circulating levels of lipids
and lipoprotein.
 Primary defects
■ reduced entry of
glucose into peripheral
tissues
■ increased liberation of
glucose into the blood
from the liver
■ “starvation in the

midst of plenty” Taken from: www.lipidsonline.org

 Manifestations
■ polyuria
■ polydipsia
■ polyphagia
■ hyperglycemia
■ glucosuria
■ pruritus
■ ketosis
■ acidosis
Taken from: dmtype1.blogspot.com

■ coma
 Insulin deficiency
Decreased glucose Increased CHON Increased lipolysis
uptake catabolism

Hyperglycemia Increased plasma a.a. Increased plasma FFA

Glycosuria Nitrogen loss (urine) Ketogenesis
Osmotic diuresis Ketonuria
Electrolyte depletion Ketonemia

Dehydration
Acidosis

Coma
Death
 Diagnosis
■ Fasting Blood Sugar (FBS)
— 80 - 110 mg/dL
■ Oral glucose tolerance test
— < 200 mg/dL (2-hour)
■ Random blood sugar —-
<200 mg/dL
■ symptoms associated with
diabetes mellitus
 Types of Diabetes
■ Type I (IDDM) DM
■ Type II (NIDDM) DM
■ Secondary Diabetes (5%)
■ Chronic Pancreatitis
■ Total Pancreatectomy
■ Cushing’s Syndrome
■ Acromegaly
■ Gigantism
■ Pregnancy
 Causes of Insulin Resistance
■ decreased ability of insulin
to increase GLUT-4
(skeletal muscle) —
Glucometabolic regulation
- Lipotoxicity
■ decreased ability of insulin
to repress hepatic glucose
production — Lipotoxicity
■ inability of insulin to
repress hormone sensitive
lipase or increase LPL.
Hemoglobin A1C (HbA1C )
■ Important circulating
product of glycation
■ Useful marker for long
term glucose regulation
■ Clinically useful for Taken from: www.centennial.rucares.org

determining disease
progression and compliance
with treatment (diabetic
control) —— (8-12 weeks)
Taken from: www.healthline.com
Complications in long-standing diabetes
■ Microvascular
■ retinopathy
■ nephropathy
■ neuropathy
■ Macrovascular
■ Attributed to accelerated atherosclerosis
stroke, MI
 HYPERGLYCEMIA

cellular glucose/cellular toxicity

synthesis polyols, hexosamines AEGs

and diacylglycerol

(+) protein kinase C (+) macrophages and

endothelial cells
oxidative stress

retina, kidney and peripheral nerves !135

 Glucagon
■ A linear polypeptide
■ Produced by A cells of the islets & upper
GIT
■ Promotes hyperglycemia
■ Half-life of 5 – 10 minutes
■ Inactivated mostly in the liver
Regulation of Insulin Secretion
Negative Feedback (Physiological response driven feedback loop)

↓ blood glucose level

(stimulus)

↑ glucagon secretion

↑ glucose level
(response)
 Principal Actions of Glucagon
■ acts on the liver and adipose tissue
■ increases glycogenolysis
■ increases gluconeogenesis
■ promotes ketogenesis
■ promotes lipilysis
■ increases urea production
Calcium and Phosphate
Metabolism
 Calcium in ECF and Soft Tissues
■ Bone: 99%
■ large reservoir
■ Extracellular pool: 1 gm
(0.1%) - (1.2 mmol/L or 2.4
meq/L
■ Intracellular pool: 9.0002
gm
■ Intracellular free: 0.2 mg
EC pool
■ Intracellular (bound to ER, IC free
mitochondria, PM): 9 gm IC bound
TOTAL DIFFUSSABLE 10 55%
Ionized calcium 5 50%
Complexed to HCO3- , 0.5 5% (9%)
Phosphate citrate, etc

TOTAL NON DIFFUSABLE 4.5 45% (41%)

Bound to albumin 3.7 37%
Bound to globulin 0.8 8%

TOTAL PLASMA CALCIUM 10 100%

few percent from the normal value of about 9.4 mg/dl, Thus, the plasma and interstitial fluids have a normal
which is equivalent to 2.4 millimoles of calcium per liter. calcium ion concentration of about 1.2 mmol/L (or
This precise control is essential because calcium plays 2.4 mEq/L, because it is a divalent ion), a level only
a key role in many physiological processes, including one-half the total plasma calcium concentration. This
contraction of skeletal, cardiac, and smooth muscles, ionic calcium is the form that is important for most
10%
blood clotting, and transmission of nerve impulses, to functions of calcium in the body, including the effect of
name just a few. Excitable cells such as neurons are sensi- calcium on the heart, the nervous system, and bone
tive to changes in calcium ion concentrations, and
Complexed formation.
increases in calcium ion concentration above normal
(hypercalcemia) 10%cause progressive depression of the Calcium complexed to
nervous system; conversely, decreases in calcium con- anions 9% (0.2 mmol/L)
centration (hypocalcemia) cause the nervous system to
become more excited.
An important feature of extracellular calcium regula-
tion is that only about 0.1 percent of the total body
Ionized 50%
calcium is in the extracellular fluid, about 1 percent is
in the cells and its organelles, and the rest is stored in Ionized calcium
50%
Protein-bound calcium
50% 41%
bones. Therefore, the bones can serve as large reservoirs, (1.2 mmol/L) (1.0 mmol/L)
Protein calcium
releasing Bound 40%
when extracellular fluid concentration
decreases and storing excess calcium.
Approximately 85 percent of the body’s phosphate is
stored in bones, 14 to 15 percent is in the cells, and less
than 1 percent is in the extracellular fluid. Although extra- Figure 80-1. Distribution of ionized calcium (Ca++), diffusible but
cellular fluid phosphate concentration is not nearly as well un-ionized calcium complexed to anions, and nondiffusible protein-
regulated as calcium concentration, phosphate serves bound calcium in blood plasma.

1001

Serum Calcium Distribution

 Chapter 80 Parathyroid Hormone, Calcitonin, Calcium and
Calcium Homeostasis
Calcium
Cells
ph
intake cal
(13,000 mg) Bone
(1000 mg/day)
(1,000,000 mg) glo
in
Absorption Deposition the
(350 mg/day) (500 mg/day)
Extracellular add
fluid ph
(1300 mg)
Secretion Resorption the
(250 mg/day) (500 mg/day)
pla
Filtration Reabsorption ph
(9980 mg/day) (9880 mg/day)
Feces
(900 mg/day) gre
Kidneys
Urine the
(100 mg/day) ph
Figure 80-3. Overview of calcium exchange between different tissue
 Pathologic Effect
■ Hypercalcemia
■ progressive depression of nervous system (sluggish) - 12mg/dL
■ decreases QT interval
■ lack of appetite
■ constipation
■ precipitation of calciumphosphate crystals
■ Hypocalcemia
■ more excitation of nervous system
■ 50% (6 mg/dL) decrease - tetany (carpopedal spasm) ——
seizures
■ 4mg/dL (lethal)
Physiologic role of Phosphate
■ key intracellular component
■ components of intermediates of
metabolism of ATP, creatine phosphate,
thiamine pyrophosphate, cAMP, DNA and
RNA
■ plays a role in protein and lipid metabolism
■ second messenger
■ serves as backbone of nucleic acid
■ biological buffer
Forms of inorganic phosphate
■ Plasma (mg/L of phosphorus)
■ HPO4
■ H2PO4

acidosis - increases H2PO4 - decreases HPO4

alkalosis - decreases H2PO4 - increases HPO4

 Body Phosphate Distribution

■ Bone: 85%
■ large reservoir
■ Extracellular pool: (<1%)
■ Intracellular pool: (14 -15%)
■ Intracellular free:
■ Intracellular (bound to
organelles)

!147
TOTAL DIFFUSSABLE 3.6 90%
Ionized phosphate 3.36 84%
Complexed to HCO3- 0.24 6%
citrate, etc

TOTAL NON DIFFUSABLE 0.4 10%

Bound to protein 0.4 10%

TOTAL PLASMA PO4 4 100%

Phosphate Homeostasis
 BONE
▪ Components
▪ collagen
▪ Ca++ (type I) and phosphate
salts (hydroapatites)
▪ Functions
▪ Involved in calcium and
phosphate homeostasis
▪ protects vital organs
▪ provides locomotion and
supports load against gravity
 Bone Cells
▪ Osteoblast (bone forming
cells)
▪ modified fibroblast with
extensive growth factor
regulation
▪ requires ossification-specific
transcription factors (Cbfa1/
Runx2) for their
differentiation
▪ can lay down type 1 collagen
and form new bone Taken from: www.saveourbones.com
 Bone Cells
▪ Osteocytes
▪ bone cells that are
formed when the
osteoblasts are
embedded in the matrix
▪ Osteoclast (bone
destroying cells)
▪ members of monocyte
family
Taken from: www.saveourbones.com
100 days T lymphocytes
Bone remodelling
Units (2M)

Modified fibroblast
Cbfa1/runx2 (differentiation
And ossification)

Monocyte / Macrophage family

Cbfa1/runx2 (differentiation
and ossification)

pH = 4.0

BONE RESORPTION
Measurement of Urinary
Pyridinolines
■ Pyridinolines
■ collagen breakdown products
■ index of the rate of bone resorption
 RANK/RANKL/OPG System
■ Osteopetrosis
■ excessive bone density
■ loss of RANKL
■ defective or loss of osteoclasts
■ Osteoporosis
■ reduce bone density (loss of bone matrix)
■ loss of OPG
■ due to high number of hyperactive osteoclast.
(Colles fracture, kyposis and window humps)
Changes in ECF level Normal level
 CALCIUM AND PO4 METABOLISM
THREE HORMONES THREE TARGET ORGANS
■ Parathyroid Hormone (PTH) ■ Bone
■ Calciotropic hormone
■ 1,25 (OH)2 D3 (Calcitriol) ■ Gastrointestinal Tract
■ Calciotropic hormone
■ Calcitonin
■ Kidney

Local Hormone
■ Parathyroid Hormone Related

Protein (PTHrP)
PARATHYROID
GLAND
Contains two distinct cells;
a) Chief cells
- most abundant
- ER, Golgi complex and
secretory granules
- secrete PTH
b) Oxyphil cells
- less abundant
- believed to be a
degenerated chief cells
- contain oxyphil granules
 Parathyroid hormone (PTH)
▪ primary hormone that
protects against
hypocalcemia
▪ primary targets are bone and
kidney
▪ also functions in positive-
feed forward loop ( +
production of 1,25 (OH)2
D 3)

Ganong. Review of Medical Physiology, 24th edition

Chief Cell
↓ Ca++ 0.2meq/L CRE)
→ ↑ 5% from
Basal)
Ganong. Review of Medical
Physiology, 24th edition
 Increases calcium reabsorption
Increases bone (thick ascending LOH and distal
resorption tubule)
Increases phosphate excretion
( - proximal tubule NPT2)
BIOLOGIC EFFECTS OF PTH
Increase the formation
of 1,25 (OH)2 D3
Increases Ca++ and PO4
(No direct action)
 PTH Excess
■ Primary Hyperparathyroidism
■ hyper-secretion from hyper- secreting
parathyroid tumor.
■ usually asymptomtic
■ characterized by
■ Hypophospathemia and phosphaturia
■ Hypercalcemia (cardiac arrest and peptic ulcer formation)
■ Hypercalciuria and elevated hydroxyproline
■ Formation of kidney stones , osteoporosis
■ Personality changes (depression) and fatigue, mental confusion or coma.
 PTH Excess
■ Secondary Hyperparathyroidism
■ due to abnormality in other organs (chronic renal
disease and Rickets ---- ↓ calcium level).
■ development of compensatory parathyroid
hypertrophy.
■ characterized by
■ Hypophospathemia
■ Hypocalcemia
■ Formation of kidney stones
■ Personality changes
 PTH Deficiency
■ Primary Hypoparathyroidism
■ hypo-secretion of PTH
■ Surgical removal or destruction
■ characterized by
■ Hyperphospathemia
■ Hypocalcemia
■ Tetany
 PTH Deficiency
■ Pseudo Hypoparathyroidism
■ signs and symptoms of hypoparathyroidism
exist.
■ due to receptor disease
■ 50% due to reduction of Gs activity
■ phosphaturic action is defective.
■ PTH level is normal or elevated
1,25 (OH)2 D3 (Calcitriol)
▪ from a prohormone vitamin
D.
85% bound to DBP
▪ hormone that protects Half life – several hours

against hypocalcemia.
▪ primary targets are GIT to a
lesser extent bone and
kidney.
▪ circulates in the blood
mainly bound to DBP and to
other proteins (0.4% free)
Ganong. Review of Medical Physiology, 24th edition
Hormone, Calcitonin, Calcium and Phosphate Metabolism, Vitamin D, Bone, and Teeth

, whereas the opposite bone Skin

lcified. Therefore, continual Cholecalciferol (vitamin D3 )
oblastic deposition and cal- Liver

es the shape of bones under Inhibition

UNIT XIV
stance, if a long bone of the 25-Hydroxycholecalciferol
then heals at an angle, the Kidney
nside of the angle causes
Activation Parathyroid
Increased resorption occurs hormone
where the bone is not com-
ncreased deposition on the 1,25-Dihydroxycholecalciferol
one and resorption on the
Intestinal
ome almost straight, espe- epithelium
he rapid remodeling of bone

Calcium- Calcium- Alkaline

binding stimulated phosphatase
tes Osteoblasts. Fracture of
protein ATPase
y activates all the periosteal
nvolved in the break. Also, Inhibition
eoblasts are formed almost Intestinal absorption of calcium
nitor cells, which are bone
lining bone, called the “bone
a short time, a large bulge of
Plasma calcium ion concentration
ganic bone matrix, followed
cium salts, develops between Figure 80-7. Activation of vitamin D3 to form 1,25-
dihydroxycholecalciferol and the role of vitamin D in controlling the
e. This area is called a callus.
plasma calcium concentration.
s use the phenomenon of
ate of fracture healing. This
compounds that we ingest in food are identical to the
Transcriptional Level
1,25 (OH)2D3
(-) 1ɑ -hydroxylase expression
(+) 24 – hydroxylase expression

Calcium Level
↓ Ca++ --- (+) 1ɑ -hydroxylase
expression
↑ PTH (indirect
↑ Ca++ --- (-) 1ɑ -hydroxylase
expression
CaSR (direct) --- PT

Phosphate Level
↓ Ca++ --- (+) 1ɑ -hydroxylase expression
 1,25 (OH)2 D3 Receptors
■ VDR
■ nuclear vitamin D receptor
■ binds to DNA sequences (vitamin D response
elements) as Retinoid X receptor (RXR)
Increases activity of Increases calcium
Increases Ca++ and PO4
osteoblasts which reabsorption (DT) and
phosphate reabsorption in in the intestines
bring about secondary
increase in osteoclast the proximal tubule) (transcellular and
activity paracellular route)
BIOLOGIC EFFECTS OF 1,25 (OH)2 D3
(+) Sodium Phosphate
Sodium Calcium
Cotransport (NPT2)
Exchanger (NCX)
 Vitamin D
■ Deficiency
■ Rickets (children)
■ abnormal growth of long bones (bowed legs) and collapse of
rib cage)
■ Osteomalacia (adult)
■ poorly calcified osteod with pain, vertebral collapse and
fractures
■ Osteoporosis (secondary to elevated PTH)
■ Metabolic
■ Hypocalcemia, Hypomagnesemia and Hypophosphatemia
 THYROID GLAND

■ FOLLICLES
■ colloid (thyroglobulin)
■ cuboidal epithelial cells
(follicular cells)

■ Two Types of Cells

■ Follicular cells -
■ secrete T3 and T4)
■ Parafollicular or C cells
■ secrete calcitonin
Inhibits bone Increases calcium and
resorption —— phosphate excretion
(-) activity of
osteoclast

CALCIUM AND PHOSPHATE LOWERING AGENT

Biologic Effects
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