The endocrine system coordinates body functions through chemical messenger systems including hormones. Hormones can act locally as neurotransmitters or at distant sites as endocrine hormones. They are classified based on their site of secretion and target cells. The pituitary gland regulates other endocrine glands and has anterior and posterior lobes that secrete hormones like growth hormone, ACTH, TSH, and oxytocin. Hormones act through cell surface receptors and intracellular signaling to regulate processes like growth, metabolism, and reproduction.

1. Endocrine system Physiology

2. Presented by/
Dr/ dina hamdy merzeban

3. Coordination of body functions occur by
interplay of several types of chemical
messenger systems

4. Neurotransmitters are released by axon terminals of neurons into the synaptic
junctions and act locally to control nerve cell functions
Endocrine hormones are released by glands or specialized cells into the circulating
blood and influence the function of target cells at another location in the body
Neuroendocrine hormones are secreted by neurons into the circulating blood and
influence the function of target cells at another location in the body
Paracrine are secreted by cells into the extracellular fluid or gap junctions and
affect neighboring target cells of a different type
Autocrine are secreted by cells into the extracellular fluid and affect the function of
the same cells that produced them

6. Cytokines
Cytokines are peptides secreted by cells into the extracellular
fluid and can function as autocrine, paracrine, or endocrine
hormones

7. Chemical
Structure of
Hormones:
Proteins and
polypeptides
Steroid hormones
Derivatives of the
amino acid tyrosine
 Hormones of the
anterior and
posterior pituitary
glands.
 Pancreatic hormones
(insulin and
glucagon)
 Parathyroid
hormone
 Calcitonin hormone
 Hormones of adrenal
cortex (cortisol and
aldosterone)
 hormones secreted
by ovaries (estrogen
and progesterone),
 testes (testosterone),
placenta (estrogen
and progesterone).
 -thyroid hormones
thyroxine and
triiodothyronine)
 The adrenal medullae
(epinephrine and
norepinephrine).

8. Feedback Control of Hormone Secretion
Negative feedback:
Most of Hormones are
regulated by Negative
Feedback that Prevents
over activity of Hormone
Systems
Positive feedback
occurs when the
biological action of the
hormone causes
additional secretion of
the hormone

9. Mechanisms of Action of
Hormones
On the surface
of the cell
membrane
In the cell
cytoplasm
In the cell
nucleus

10. INTRACELLULAR
SIGNALING AFTER
HORMONE RECEPTOR
ACTIVATION:

11. CELL
SURFACE
RECEPTROS
Ion Channel–Linked Receptors: Virtually all the
neurotransmitter substances, such as acetylcholine
and norepinephrine, combine with receptors in the
postsynaptic membrane
Enzyme-Linked Hormone Receptors
GTP-binding proteins : The trimeric G proteins are
named for their ability to bind guanosine
nucleotides
Second Messenger Mechanisms for Mediating
Intracellular Hormonal Functions

12. CELL
SURFACE
RECEPTROS
◦ Ion Channel–Linked Receptors: Virtually all the
neurotransmitter substances, such as acetylcholine
and norepinephrine, combine with receptors in the
postsynaptic membrane. This almost always causes a
change in the structure of the receptor, usually
opening or closing a channel for one or more ions.
Many hormones activate receptors that indirectly
regulate the activity of target proteins (e.g., enzymes
or ion channels) by coupling with groups of cell
membrane proteins called heterotrimeric

13. CELL
SURFACE
RECEPTROS
◦Enzyme-Linked Hormone
Receptors. Some receptors, when
activated, function directly as
enzymes or are closely associated
with enzymes that they activate.
◦e.g. tyrosine kinase activity of
insulin receptors

14. CELL
SURFACE
RECEPTROS
◦ GTP-binding proteins (G proteins): The trimeric G
proteins are named for their ability to bind guanosine
nucleotides. In their inactive state, the α, β, and γ
subunits of G proteins form a complex that binds
guanosine diphosphate (GDP) on the α subunit.
◦ When the receptor is activated, it undergoes a
conformational change that causes the GDP-bound
trimeric G protein to associate with the cytoplasmic
part of the receptor and to exchange GDP for
guanosine triphosphate (GTP).
◦ the α subunit dissociate from the trimeric complex
and associate with other intracellular signaling
proteins; these proteins, in turn, alter the activity of
ion channels or intracellular enzymes.

16. CELL
SURFACE
RECEPTROS
◦Second Messenger Mechanisms for
Mediating Intracellular Hormonal
Functions
◦One of the means by which hormones exert
intracellular actions is to stimulate
formation of the second messenger inside
the cell membrane.
◦the second messenger then causes
subsequent intracellular effects of the
hormone.

17. Second
Messenger
Mechanisms
for
Mediating
Intracellular
Hormonal
Functions
adenylyl Cyclase cAMP Second Messenger System
:
Binding of the hormones with the receptor causes
Stimulation of adenylyl cyclase, a membrane-
bound enzyme then catalyzes the conversion of a
small amount of cytoplasmic adenosine
triphosphate (ATP) into cAMP inside the cell.
This then activates cAMP-dependent protein
kinase, (PKA) which phosphorylates specific
proteins in the cell, triggering biochemical
reactions that ultimately lead to the cell’s response
to the hormone.

18. Adenylyl Cyclase cAMP Second
Messenger System
Binding of the hormones with
the receptor causes Stimulation
of adenylyl cyclase, a
membrane-bound enzyme then
catalyzes the conversion of a
small amount of cytoplasmic
adenosine triphosphate into
cAMP inside the cell
This then activates cAMP-
dependent protein kinase,
which phosphorylates specific
proteins in the cell, triggering
biochemical reactions that
ultimately lead to the cell’s
response to the hormone

19. This Photo by Unknown author is licensed under CC BY-SA.

20. Second
Messenger
Mechanisms
for
Mediating
Intracellular
Hormonal
Functions
Cell Membrane Phospholipid Second Messenger System :
Some hormones activate transmembrane receptors that activate the enzyme
phospholipase C attached to the inside projections of the receptors. This
enzyme catalyzes the breakdown of some phospholipids in the cell membrane,
especially phosphatidylinositol Biphospahte (PIP2), into two different second
messenger products: inositol triphosphate (IP3) and diacylglycerol (DAG). The
IP3 mobilizes calcium ions from mitochondria and the endoplasmic reticulum,
and the calcium ions then have their own second messenger effects, such as
smooth muscle contraction and changes in cell secretion. DAG, the other lipid
second messenger, activates the enzyme protein kinase C (PKC), which then
phosphorylates a large number of proteins, leading to the cell’s response.

22. This Photo by Unknown author is licensed under CC BY-SA-NC.

23. Second
Messenger
Mechanisms
for
Mediating
Intracellular
Hormonal
Functions
Calcium-Calmodulin Second Messenger System
Another second messenger system operates in response to the
entry of calcium into the cells. Calcium entry may be initiated by:
Changes in membrane potential that open calcium
channels.
A hormone interacting with membrane receptors that open
calcium channels.
◦ On entering a cell, calcium ions bind with the protein
calmodulin. This protein has four calcium sites, and when
three or four of these sites have bound with calcium, the
calmodulin changes its shape and initiates multiple effects
inside the cell, including activation or inhibition of protein
kinases.

25. INTRACELLULAR
RECEPTROS
• Several hormones, including adrenal and gonadal steroid
hormones, thyroid hormones, retinoid hormones, and vitamin D
• lipid soluble hormones readily cross the cell membrane and
interact with receptors in the cytoplasm or nucleus. The activated
hormone-receptor complex then binds with a specific regulatory
(promoter) sequence of the DNA called the hormone response
element, and in this manner either activates or represses
transcription of specific genes and formation of mRNA. Therefore,
minutes, hours, or even days after the hormone has entered the
cell, newly formed proteins appear in the cell and become the
controllers of new or altered cellular functions.

26. “GENOMIC ACTIONS”
Cytoplasmic
receptors: Steroid
Hormones : Sex
hormones, Adrenal,
Vitamin D
Nuclear receptors:
Thyroid hormone

27. Pituitary
The Pituitary Gland Has Two Distinct Parts— The
Anterior and Posterior Lobes

28. ANTERIOR PITUITARY
Somatotropes secrete: human
growth hormone
Corticotropes secrete:
adrenocorticotropin
Thyrotropes secrete: thyroid-
stimulating hormone

29. ANTERIOR PITUITARY
• Gonadotropes secrete: gonadotropic hormones, which include both
luteinizing hormone and follicle-stimulating hormone
• Lactotropes secrete: prolactin

30. POSTERIOR PITUITARY
• Antidiuretic hormone controls the rate of water excretion into the urine,
thus helping to control the concentration of water in the body fluids

31. POSTERIOR PITUITARY
• Oxytocin helps express milk from the glands of the breast to the nipples during suckling and
helps in the delivery of the baby at the end of gestation
• Thyrotropin-releasing hormone , which causes release of thyroid- stimulating hormone
• Corticotropin-releasing hormone , which causes release of adrenocorticotropin
• Growth hormone–releasing hormone , which causes release of growth hormone, and growth
hormone inhibitory hormone , also called somatostatin, which inhibits release of growth
hormone
• Gonadotropin-releasing hormone , which causes release of the two gonadotropic hormones,
luteinizing hormone and follicle- stimulating hormone
• Prolactin inhibitory hormone , which causes inhibition of prolactin secretion

32. GROWTH HORMONE
It is a polypeptide hormone also called Somatotropin

33. Mechanism of action :
• STAT5 transcription factors, , which leads to
initiation of transcription of certain genes for protein
synthesis
• Insulin receptor substrates 1 that lead to the
activation of enzymes involved in the metabolic
processes in the cell
• Phosphorylation of MAPK

34. PHYSIOLOGICAL FUNCTIONS OF
GROWTH HORMONE
• Enhancement of Amino Acid Transport through the Cell Membranes
• Enhancement of RNA Translation to Cause Protein Synthesis by the Ribosomes
Protein: Growth Hormone Promotes Protein Deposition in Tissues
Increased Nuclear Transcription of DNA to Form RNA
Lipids: Growth Hormone Enhances Fat Utilization for Energy and leading to release
of ketone bodies “Ketogenic” Effect
• Decreased glucose uptake in tissues such as skeletal muscle and fat
• Increased glucose production by the liver
• Increased insulin secretion
Carbohydrates: Growth Hormone Decreases Carbohydrate Utilization Growth
hormone causes multiple effects that influence carbohydrate metabolism, including
Growth Hormone Stimulates visceral growth

35. PHYSIOLOGICAL
FUNCTIONS OF
GROWTH HORMONE
Growth Hormone Stimulates Cartilage and Bone Growth

36. PHYSIOLOGICAL FUNCTIONS OF
GROWTH HORMONE
• Decreased secretion
• PANHYPOPITUITARISM: This term means decreased secretion of all the anterior pituitary hormones
• SHEEHAN’S SYNDROME: Happens as a result of sever postpartum hemorrhage that leads to destruction
of anterior pituitary hormones
• PITUITARY DWARFISM. Most instances of dwarfism result from deficiency of GH secretion during
childhood
• Increased secretion
• GIGANTISM. Occasionally, growth hormone– producing cells of the anterior pituitary gland become
excessively active
• ACROMEGALY. If a tumor occurs AFTER adolescence— that is, after the epiphyses of the long bones have
fused with the shafts—the person cannot grow taller, but the bones can become thicker and the soft tissues
can continue to grow

37. PHYSIOLOGICAL FUNCTIONS OF
GROWTH HORMONE
• Enlargement is especially marked in the bones of the hands and feet and
in the membranous bones, including the cranium, nose, bosses on the
forehead, supraorbital ridges, lower jawbone, and portions of the
vertebrae, because their growth does not cease at adolescence

38. PROLACTIN
In females: Amenorrhea and galactorrhea In males: Infertility
In both sexes: decreased libido
Treatmentofhyperprolactinemia:Dopamineagon
ist

39. POSTERIOR
PITUITARY GLAND
• Antidiuretic hormone , also called
vasopressin, formed primarily in the
supraoptic nuclei
• Oxytocin

40. ANTIDIURETIC HORMONE
• V1 : Acts via G coupled protein by inositol phosphate pathway , to increase intracellular Ca2+
• V2 : Acts through G coupled protein of Adenyl cyclase pathway that increases the intracellular cAMP
• V3 : Acts through G coupled protein on phospholipase
• RENAL EFFECTS
• ON BLOOD VESSELS
• In case of STRESS
• Hypovolemia, >> results in a decrease in atrial pressure and central venous pressure >> decreased firing of atrial stretch
receptors >> Afferent nerve fibers from these receptors synapse
• Hypotension,whichdecreasesarterial baroreceptorfiring,leadsto enhanced sympathetic activity that increases AVP release
• Hypothalamic osmoreceptors sense extracellular osmolarity and stimulate AVP release when osmolarity rises, as occurs
with dehydration

41. ANTIDIURETIC HORMONE
• Angiotensin II receptors located in a region of the hypothalamus regulate AVP release – an
increase in angiotensin II simulates AVP release
• Stress: increases ADH through CRH-ADH
• Drugs: Morphine, Nicotine, Anesthesia
• Low osmolarity of the plasma
• Hypervolemia
• α- Adrenergic stimulation
• Ethyl Alcohol
• Diabetes insipidus
• SyndromeofInappropriateAntidiureticHormoneSecretion

42. OXYTOCIN
Mechanism of Action: Binds to G-protein coupled receptor to increase cytoplasmic Ca+ level which in order increases smooth muscle
contraction
In Male: contraction of the vas deferens
Females: Contraction of the uterus
helps semen transport into the uterus
During labor: Strong uterine contraction
to expel the baby
During lactation: myoepithlial cells
contraction to squeeze the milk
Conditioned reflex: Higher centers stimulation: Seeing, Hearing the cry of baby, smelling, or just thinking of the baby
Mechanism of secretion: Neurohormonal reflex
Unconditioned reflex
• Genital manipulation
• Massage of the nipple during lactation

43. ◦ Decreased secretion
◦ PANHYPOPITUITARISM: This term means decreased secretion of all the anterior pituitary
hormones
◦ SHEEHAN’S SYNDROME: Happens as a result of sever postpartum hemorrhage that leads to
destruction of anterior pituitary hormones
◦ PITUITARY DWARFISM. Most instances of dwarfism result from deficiency of GH secretion during
childhood
◦ Increased secretion
◦ GIGANTISM. Occasionally, growth hormone– producing cells of the anterior pituitary gland
become excessively active
◦ ACROMEGALY. If a tumor occurs AFTER adolescence— that is, after the epiphyses of the long
bones have fused with the shafts—the person cannot grow taller, but the bones can become
thicker and the soft tissues can continue to grow

44. Mechanisms of Action of
Hormones
In the cell nucleus
◦ Enlargement is especially marked in the bones of the hands and feet and in the
membranous bones, including the cranium, nose, bosses on the forehead,
supraorbital ridges, lower jawbone, and portions of the vertebrae, because their
growth does not cease at adolescence
◦ In females: Amenorrhea and galactorrhea
◦ In males: Infertility
◦ In both sexes: decreased libido
◦ Treatmentofhyperprolactinemia:Dopamineagonist

45. POSTERIOR
PITUITARY
GLAND
Antidiuretic hormone , also called vasopressin, formed primarily in
the supraoptic nuclei
◦ Oxytocin

46. ANTIDIURETIC HORMONE
V1 : Acts via G coupled protein by
inositol phosphate pathway , to
increase intracellular Ca2+
V2 : Acts through G coupled protein
of Adenyl cyclase pathway that
increases the intracellular cAMP
V3 : Acts through G coupled protein
on phospholipase
•RENAL EFFECTS
•ON BLOOD VESSELS
•In case of STRESS
Hypovolemia, >> results in a
decrease in atrial pressure and
central venous pressure >>
decreased firing of atrial stretch
receptors >> Afferent nerve fibers
from these receptors synapse
Hypotension,whichdecreasesarterial
baroreceptorfiring,leadsto enhanced
sympathetic activity that increases
AVP release
Hypothalamic osmoreceptors sense
extracellular osmolarity and
stimulate AVP release when
osmolarity rises, as occurs with
dehydration

47. ANTIDIURET
IC
HORMONE
Angiotensin II receptors located in a region of the
hypothalamus regulate AVP release – an increase in
angiotensin II simulates AVP release
Stress: increases ADH through CRH-ADH
Drugs: Morphine, Nicotine, Anesthesia
Low osmolarity of the plasma
Hypervolemia
α- Adrenergic stimulation
Ethyl Alcohol
Diabetes insipidus
SyndromeofInappropriateAntidiureticHormoneSecretion
Causes: Drugs Cancer

48. OXYTOCIN
Mechanism of secretion: Neurohormonal reflex
Unconditioned reflex
•Genital manipulation
•Massage of the nipple during lactation
Conditioned reflex: Higher centers stimulation: Seeing, Hearing the cry of baby, smelling, or just thinking of the baby
Mechanism of Action: Binds to G-protein coupled receptor to increase cytoplasmic Ca+ level which in order increases smooth muscle contraction
In Male: contraction of the vas deferens
Females: Contraction of the uterus helps semen transport into the uterus
During labor: Strong uterine contraction to expel the baby
During lactation: myoepithlial cells contraction to squeeze the milk

49. THYROID
GLAND
GLUT4 is insulin dependent, it’s contained in vesicles in the
cytoplasm, these vesicles move to the cell membrane once
Insulin binds to its receptor
Non- insulin dependent tissues , have glucose transporters on
the cell membrane in absence of Insulin
EXERCISE increases the movement of GLUT4 vesicles towards
cell membrane through the action of 5’AMP activated kinase

50. MECHANISM OF INSULIN
SECRETION
The beta cells have a large number of glucose transporters that permit a rate of glucose influx that is
proportional to the blood concentration in the physiological range
Glucose is phosphorylated to glucose-6-phosphate by glucokinase
The glucose-6-phosphate is subsequently oxidized to form adenosine triphosphate
ATP inhibits the ATP-sensitive potassium channels of the cell
Opening voltage-gated calcium channels, which are sensitive to changes in membrane voltage
Influx of calcium that stimulates fusion of the docked insulin- containing vesicles with the cell
membrane and secretion of insulin into the extracellular fluid by exocytosis
ON CARBOHYDRATE METABOLISM
N.B: There is Lack of Effect of Insulin on Glucose Uptake and Usage by the Brain

51. MECHANISM OF INSULIN
SECRETION
ON LIPID METABOLISM
◦ Insulin has several effects that lead to fat storage in adipose tissue
◦ Increases Fat synthesis in the liver, the glucose is first split to pyruvate in the
glycolytic pathway, and the pyruvate subsequently is converted to acetyl coenzyme A
, the substrate from which fatty acids are synthesized
◦ Most of the fatty acids are then synthesized within the liver and used to form
triglycerides, the usual form of storage fat
◦ Insulin inhibits the action of hormone-sensitive lipase
◦ Insulin promotes glucose transport through the cell membrane into the adipose
tissue cells in the same way that it promotes glucose transport into muscle cells

52. MECHANISM OF INSULIN
SECRETION
ON PROTEIN METABOLISM AND GROWTH
◦ Insulin stimulates transport of many of the amino acids into the cells
◦ Insulin increases the translation of messenger RNA, thus forming new proteins
◦ Over a longer period of time, insulin also increases the rate of transcription of
selected DNA genetic sequences in the cell nuclei, thus forming increased quantities
of RNA and still more protein synthesis
◦ Insulin inhibits the catabolism of proteins, thus decreasing the rate of amino acid
release from the cells, especially from the muscle cells
◦ In the liver, insulin depresses the rate of gluconeogenesis
◦ Insulin and Growth Hormone Interact Synergistically to Promote Growth

53. MECHANISM OF INSULIN
SECRETION
Promotes Muscle Glucose Uptake and Metabolism to produce energy during exercise
Promotes glucose uptake and oxidation by all tissues
Storage of Glycogen in Muscle
Insulin Promotes Liver Uptake, Storage, and Use of Glucose
◦ Insulin inactivates liver phosphorylase, the principal enzyme that causes liver glycogen to split
into glucose
◦ Increases the activity of the enzyme glucokinase, which is one of the enzymes that causes the
initial phosphorylation of glucose
◦ Promotesglycogensynthesis,includingespeciallyglycogen synthase
◦ Insulin Promotes Conversion of Excess Glucose into Fatty Acids and Inhibits Gluconeogenesis in
the Liver

54. CONTROL OF
INSULIN
SECRETION
Insulin causes K+ to enter the cells
through its activation of Na+-K+
ATPase
K+ depletion causes inhibition of
Insulin secretion , this happens in 1ry
Hyperaldosteronism and patients
treated with thiazide diuretic)

55. INSULINOMA—
HYPERINSULINISM About 10 to 15 percent of these adenomas are
malignant, In case of high levels of insulin cause
blood glucose to fall to low values, the metabolism
of the central nervous system becomes depressed
Consequently, in patients with insulin-secreting
tumors or in patients with diabetes who administer
too much insulin to themselves, the syndrome
called insulin shock may occur as follows
Proper treatment for a patient who has
hypoglycemic shock or coma is immediate
intravenous administration of large quantities of
glucose

56. GLUCAGON
Breakdown of liver glycogen
Increased gluconeogenesis in the liver

57. PHYSIOLOGICAL ACTIONS OF
GLUCAGON
Increased Blood Glucose Concentration
◦ Glucagon activates adenylyl cyclase in the hepatic cell
membrane
◦ Which causes the formation of cyclic adenosine
monophosphate
◦ Which activates protein kinase regulator protein
◦ Which activates protein kinase
◦ Which activates phosphorylase b kinase
◦ Which converts phosphorylase b into phosphorylase a
◦ Which promotes the degradation of glycogen into
glucose-1- phosphate
◦ Which is then dephosphorylated; and the glucose is
released from the liver cells

58. Glucagon Increases
Gluconeogenesis
Stimulates lipolysis, Keogenesis and fat
utilization for energy production

59. Regulation of Glucagon
Secretion
Increased Blood Glucose Inhibits
Glucagon Secretion

60. Regulation of
Glucagon
Secretion
Increased Blood Amino Acids Stimulate Glucagon Secretion
Exercise Stimulates Glucagon Secretion

61. SOMATOSTATIN
Somatostatin acts locally within the islets of Langerhans in
a paracrine way to depress the secretion of both insulin
and glucagon
Somatostatin decreases the motility of the stomach,
duodenum, and gallbladder
Somatostatindecreasesbothsecretionandabsorptioninthe
gastrointestinal tract

62. SUMMARY OF BLOOD
GLUCOSE
REGULATION
The liver acts as a Glucostat : That is, when the blood glucose rises to a
high concentration after a meal and the rate of insulin secretion also
increases, as much as two thirds of the glucose absorbed from the gut is
almost immediately stored in the liver in the form of glycogen
Both insulin and glucagon function as important feedback control
systems for maintaining a normal blood glucose concentration
Also, in severe hypoglycemia, a direct effect of low blood glucose on the
hypothalamus stimulates the sympathetic nervous system
And finally, over a period of hours and days , both growth hormone and
cortisol are secreted in response to prolonged hypoglycemia

63. Importance of Blood Glucose
Regulation
In case of hypoglycemia: Glucose is the only nutrient that normally
can be used by the brain, retina, and germinal epithelium of the
gonads in sufficient quantities to supply them optimally with their
required energy

64. In case of
hyperglycemi
a
Glucose can exert a large amount of osmotic pressure in the
extracellular fluid, and if the glucose concentration rises to
excessive values, this can cause considerable cellular
dehydration
An excessively high level of blood glucose concentration causes
loss of glucose in the urine
Loss of glucose in the urine also causes osmotic diuresis by the
kidneys, which can deplete the body of its fluids and
electrolytes
Long-term increases in blood glucose may cause damage to
many tissues, especially to blood vessels

65. DIABETES MELLITUS
Type I diabetes, also called
insulin-dependent diabetes
mellitus , is caused by lack of
insulin secretion
Type II diabetes, also called
non-insulin-dependent
diabetes mellitus , and is
initially caused by decreased
sensitivity of target tissues to
the metabolic effect of insulin

66. DIABETES
MELLITUS
Microvasularcomplications:retinopathy,peripheralneur
opathy, Nephropathy
Macrovasular complications: Atherosclerosis, Ischemic
heart diseases, cerebrovascularStrokes
Fasting blood glucose more than: 126 mg/dl
HBA1C more than: 6.4 %
Homeostatic model assessment index: evaluates B-cell
function and Insulin resistance

67. Adrenal gland There are two adrenal glands, one
at the superior pole of each
kidney
The adrenal glands are essential
for life
Severe illness results from their
atrophy and death follows their
complete removal

68. CELL SURFACE RECEPTROS
Ion Channel–Linked Receptors: Virtually all the neurotransmitter
substances, such as acetylcholine and norepinephrine, combine
with receptors in the postsynaptic membrane
GTP-binding proteins : The trimeric G proteins are named for their
ability to bind guanosine nucleotides
Enzyme-Linked Hormone Receptors
Second Messenger Mechanisms for Mediating Intracellular
Hormonal Functions

69. Adenylyl Cyclase cAMP Second
Messenger System
Binding of the hormones with the receptor causes Stimulation of
adenylyl cyclase, a membrane-bound enzyme then catalyzes the
conversion of a small amount of cytoplasmic adenosine
triphosphate into cAMP inside the cell
This then activates cAMP-dependent protein kinase, which
phosphorylates specific proteins in the cell, triggering biochemical
reactions that ultimately lead to the cell’s response to the
hormone

70. Cell Membrane
Phospholipid Second
Messenger System
Calcium-
Calmodulin
Second
Messenger
System
Another second
messenger
system operates
in response to the
entry of calcium
into the cells
Changes in
membrane
potential that
open calcium
channels
A hormone
interacting with
membrane
receptors that
open calcium
channels

71. INTRACELLULAR
RECEPTROS

72. “GENOMIC ACTIONS”
Intracellular Hormone
Receptors and
Activation of Genes
Cytoplasmic receptors:
Steroid Hormones : Sex
hormones, Adrenal,
Vitamin D
Nuclear receptors:
Thyroid hormone

73. Pituitary
The Pituitary Gland Has Two Distinct Parts— The Anterior and
Posterior Lobes

74. ANTERIOR PITUITARY
Somatotropes
secrete: human
growth hormone
Corticotropes
secrete:
adrenocorticotropin
Thyrotropes
secrete: thyroid-
stimulating
hormone

75. ANTERIOR PITUITARY
Gonadotropes secrete: gonadotropic hormones, which include
both luteinizing hormone and follicle-stimulating hormone
◦ Lactotropes secrete: prolactin

76. POSTERIOR PITUITARY
Antidiuretic hormone controls the rate of water excretion into the
urine, thus helping to control the concentration of water in the
body fluids

77. POSTERIOR PITUITARY
Oxytocin helps express milk from the glands of the breast to the nipples during suckling and
helps in the delivery of the baby at the end of gestation
◦ Thyrotropin-releasing hormone , which causes release of thyroid- stimulating hormone
◦ Corticotropin-releasing hormone , which causes release of adrenocorticotropin
◦ Growth hormone–releasing hormone , which causes release of growth hormone, and
growth hormone inhibitory hormone , also called somatostatin, which inhibits release of
growth hormone
◦ Gonadotropin-releasing hormone , which causes release of the two gonadotropic
hormones, luteinizing hormone and follicle- stimulating hormone
◦ Prolactin inhibitory hormone , which causes inhibition of prolactin secretion

78. POSTERIOR PITUITARY
Oxytocin helps express milk from the glands of the breast to the
nipples during suckling and helps in the delivery of the baby at the
end of gestation
◦ Hypothalamo-hypophyseal tract connects Hypothalamus with
posterior pituitary

79. GROWTH HORMONE
It is a polypeptide hormone also called Somatotropin

80. Mechanism
of action :
STAT5 transcription factors, , which
leads to initiation of transcription
of certain genes for protein
synthesis
Insulin receptor substrates 1 that
lead to the activation of enzymes
involved in the metabolic
processes in the cell
Phosphorylation of MAPK

81. PHYSIOLOGICAL
FUNCTIONS OF
GROWTH
HORMONE
Protein: Growth Hormone Promotes Protein Deposition in Tissues
Lipids: Growth Hormone Enhances Fat Utilization for Energy and leading to release of ketone bodies “Ketogenic” Effect
Enhancementof Amino Acid Transport through the Cell Membranes
Enhancementof RNA Translation to Cause Protein Synthesis by the Ribosomes
Increased Nuclear Transcription of DNA to Form RNA
Carbohydrates: Growth Hormone Decreases Carbohydrate UtilizationGrowth hormone causes multiple effects that influence
carbohydrate metabolism, including
Decreased glucose uptake in tissues such as skeletal muscle and fat
Increased glucose production by the liver
Increased insulin secretion

82. Growth Hormone
Stimulates Cartilage and
Bone Growth
Although growth hormone stimulates increased
deposition of protein and increased growth in
almost all tissues of the body, its most obvious
effect is to increase growth of the skeletal frame
This results from multiple effects of growth
hormone on bone, including increased deposition
of protein both in cartilage and bones causing
formation of new cartilage and bone cells
These effects lead to increased length of the bones
before puberty and increased thickness of the
bones after puberty

83. GROWTH HORMONE EXERTS MUCH
OF ITS EFFECT THROUGH
INTERMEDIATE SUBSTANCES
CALLED “SOMATOMEDINS”
Growth Hormone Stimulates visceral growth

84. PROLACTIN Thyroglobulin synthesis : glycoprotein produced by the follicular cells of the
thyroid and used entirely within the thyroid gland to form T3 and T
Iodide trapping
The basal membrane of the thyroid cell has the specific ability to pump the
The energy for transporting iodide against a concentration gradient comes from
the sodium-potassium ATPase pump, which pumps sodium out of the cell,
thereby establishing a low intracellular sodium concentration and a gradient for
Iodide is transported out of the thyroid cells across the apical membrane into
the follicle by a chloride-iodide ion counter-transporter molecule

85. PROLACTIN Oxidation: The first essential step in the formation of the thyroid
hormones is conversion of the iodide ions to an oxidized form of iodine,
that is then capable of combining directly with the amino acid tyrosine
Iodination of Tyrosine and Formation of the Thyroid Hormones
“Organification” of Thyroglobulin: The binding of iodine with the
thyroglobulin molecule is called organification of the thyroglobulin
COUPLING
Thyroxine , which is formed when two molecules of diiodotyrosine are
joined together; the thyroxine then remains part of the thyroglobulin
molecule
Triiodothyronine , one molecule of monoiodotyrosine couples with one
molecule of diiodotyrosine

86. PROLACTIN
Release of Thyroxine and Triiodothyronine from the Thyroid Gland:
Thyroglobulin itself is not released into the circulating blood in
measurable amounts; instead, thyroxine and triiodothyronine
must first be cleaved from the thyroglobulin molecule, and then
these free hormones

87. PROLACTIN
Daily Rate of Secretion of Thyroxine and Triiodothyronine: About
93 percent of the thyroid hormone released from the thyroid
gland is normally thyroxine and only 7% is triiodothyronine
However, during the next few days, about one half of the
thyroxine is slowly deiodinated to form additional triiodothyronine

88. Mechanism of Action
Non-Genomic Actions: include the
regulation of ion channels and
oxidative phosphorylation and appear
to involve the activation of
intracellular secondary messengers
such as cyclic AMP or protein kinase
signaling cascades

89. PHYSIOLOGICAL FUNCTIONS OF THE THYROID
HORMONES
Increase the
metabolic activities
of almost all the
tissues of the body
Effect of Thyroid
Hormone on
Growth

90. PHYSIOLOGICAL FUNCTIONS OF THE
THYROID HORMONES
Effects of Thyroid Hormone on Metabolism
Effect of Thyroid Hormone on Sexual Function : For normal sexual function, thyroid secretion needs to be approximately
normal
Increased Requirement for Vitamins
On Body Weight: Greatly increased thyroid hormone almost always decreases the body weight, and greatly decreased
thyroid hormone almost always increases the body weight
On plasma lipids: thyroid hormones decrease plasma cholesterol and increase its secretion in bile and stool
Effect on CVS
On CNS : Thyroid has an excitatory effect on the CNS functions : A- Muscle tremors
Other endocrine glands: thyroid hormone increases the levels of insulin, cortisol and parathyroid hormone

91. REGULATION OF THYROID
HORMONE SECRETION
TSH : Increases Thyroid Secretion
◦ Cyclic Adenosine Monophosphate Mediates the Stimulatory Effect of
TSH
◦ Increased proteolysis of the thyroglobulin that has already been stored
in the follicles
◦ Increased activity of the iodide pump, which increases the rate of
“iodide trapping” in the glandular cells
◦ Increased iodination of tyrosine to form the thyroid hormones
◦ Increased size and increased secretory activity of the thyroid cells

92. N.B. ANTERIOR PITUITARY
SECRETION OF TSH IS
REGULATED BY THYROTROPIN-
RELEASING HORMONE FROM
THE HYPOTHALAMUS
Effect of change in temperature

93. N.B. ANTERIOR PITUITARY
SECRETION OF TSH IS
REGULATED BY THYROTROPIN-
RELEASING HORMONE FROM
THE HYPOTHALAMUS
Feedback mechanism

94. ABNORMALITIES OF
THE THYROID
HORMONE

95. Hyperthyroidism
Graves’ disease, the most common
form of hyperthyroidism, is an
autoimmune disease in which
antibodies called thyroid-stimulating
immunoglobulins
Thyroid Adenoma

96. Hyperthyroidism
Nervousness and high excitability

97. Hyperthyroidism
Intolerance to heat and increased sweating
◦ Weight loss
◦ Tremors of the hands
◦ Exophthalmos
◦ Tachycardia and palpitations

98. Hypothyroidism
Myxedema: Hypothyroidism
in adult life, characterized by
cold intolerance, depressed
mental and sexual functions,
husky voice, and weight gain
Cretinism: Hypothyroidism
in the neonatal period, lead
to irreversible mental,
physical and sexual growth
retardation

99. ENDOCRINE PANCREAS
The acini, which secrete digestive juices into the duodenum

100. ENDOCRINE PANCREAS
The islets of Langerhans, which secrete insulin and glucagon
directly into the blood

101. ENDOCRINE
PANCREAS
The beta cells, constituting about 60 percent
of all the cells of the islets, lie mainly in the
middle of each islet and secrete insulin
The alpha cells, about 25 percent of the total,
secrete glucagon
The delta cells, about 10 percent of the total,
secret somatostatin
The PP cell, is present in small numbers in the
islets and secretes a hormone called
pancreatic polypeptide

102. INSULIN
Insulin receptor is a combination of
four subunits held together by
disulfide linkages: two alpha
subunits that lie entirely outside the
cell membrane and two beta
subunits that penetrate through the
membrane, protruding into the cell
cytoplasm
NB: Overlap in the secretions of
androgens and glucocorticoids exist
between the fasciculata and
reticularis
Being lipophilic, the adrenocortical
hormones are all carried in the blood
extensively bound to plasma proteins
Cortisol is bound mostly to a plasma
protein specific for it called
corticosteroid binding globulin ,
about 15% is bound to albumin, only
10% is free

103. INSULIN
Rapid : Cell membrane becomes more
permeable to Glucose, K+

104. INSULIN
Intermediate : Change the activity of intracellular enzymes
◦ Secondary Active transport: – SGLT1, SGLT2; SGLT2 inhibitors are widely used for lowering blood glucose as they
increase glucose loss in urine
◦ Facilitated Diffusion: GLUT 1- GLUT7
◦ Zona glomerulosa
◦ Zona fasciculata
◦ Zona reticularis
◦ Hormones produced by the adrenal cortex are steroids derived from the common precursor cholesterol
◦ These comprise mineralocorticoids, glucocorticoids and sex hormones
◦ The three categories of adrenal steroids are produced in anatomically distinct portions of the adrenal cortex as a
result of differential distribution of the enzymes required to catalyze the different biosynthetic pathways leading to
the formation of each of these steroids
◦ Zona Glomerulosa

105. INSULIN
Intermediate : Change the activity of intracellular enzymes
◦ Outermost zone – just below the adrenal capsule is very thin and secretes
mineralocorticoids
◦ They maintain Na+ and K+ balance and ECF volume
◦ Mineralocorticoid of most importance is aldosterone
◦ Zona Fasciculata
◦ It is the middle widest zone – between the glomerulosa and reticularis
◦ Primary secretion is glucocorticoids
◦ Glucocorticoids play a major role in glucose metabolism, as well as protein and lipid
metabolism
◦ Zona Reticularis

106. Mineralocorticoids
¯It regulates the electrolyte
concentrations of extracellular fluids
¯Mineralocorticoids include mainly
aldosterone and deoxy-
corticosterone
¯Mineralocorticoids are essential for
life, without aldosterone, a person
rapidly dies from circulatory shock

107. Action of aldosterone
NB: Aldosterone also increases Na+ absorption from other body
fluid as well as from GIT mucosa
Angiotensin II stimulates conversion of corticosterone to
aldosterone in the zona glomerulosa cells and secretion of
aldosterone from these cells
Direct stimulation of adrenal cortex by a rise in plasma K+
concentration

108. Glucocorticoids
Physiological actions of glucocorticoids

109. GLUCOCORTICOIDS
Effect on metabolism

110. Glucocorticoids
Stimulation of gluconeogenesis by the
liver
Decrease the utilizationof glucose by
muscle and adipose tissue and lowers
their sensitivity to insulin
Increase protein degradation in many
tissue especially muscle, increases the
blood amino acid concentration, thus
providing more amino acids to liver or
for tissue repair
Decreased protein synthesis
Increase lipolysis (the mobilized fatty
acids are available as an alternative
metabolic fuel for tissues that can use
this energy source as an alternativeto
glucose, conserving glucose for the
brain
In diabetics, it increases ketone body
formation
Permissive action
Role in adaptation to stress

111. Glucocorticoids
Gluconeogenesis
Rises in blood
glucose, fatty
acids, and amino
acids

112. Glucocorticoids Other effects
Cortisol has a very slight mineralocorticoid activity
During fetal life, cortisol accelerates the maturation of surfactant in the lung
When cortisol or synthetic cortisol like compounds are administered to yield higher than
physiologic concentrations of glucocorticoids during treatment of certain diseases; or in case
of its hypersecretion by adrenal cortex
Corticosteroids are anti-inflammatory and immunosuppressive
It suppress the inflammatory reaction by reducing phagocytic action of white blood cells ,
inhibiting release of the lysosomal enzymes and decreasing capillary permeability
Suppresses allergic reactions by preventing release of histamine from the mast cells

113. Glucocorticoids Other undesirable effects may be observed with
prolonged exposure to higher than normal
concentrations of glucocorticoids
Cortisol increases the production of red blood cells by
mechanisms that are unclear
The administration of large doses of cortisol causes
significant atrophy of all the lymphoid tissue
throughout the body, which in turn decreases the
output of both T cells and antibodies from the
lymphoid tissue

114. Glucocorticoids
NB: This occasionally can lead to fulminating infection and death
from diseases that would otherwise not be lethal, such as
fulminating tuberculosis in a person whose disease had previously
been arrested

115. Glucocorticoids
Hypothalamic control is via CRH
CRH is secreted into the hypothalamic-hypophyseal portal blood and sent to the anterior pituitary
CRH binds to receptors causing synthesis of POMC a precursor of ACTH
POMC is a large precursor of MSH, and β- endorphin
ACTH being tropic to zona fasciculata and zona reticularis
Negative feedback system involving the hypothalamus and anterior pituitary
Diurnal rhythm: The plasma cortisol concentration display a characteristic diurnal rhythm, with the
highest level occurring in the morning and lowest level at mid night
Stress: The magnitude of the increase in plasma cortisol concentration is proportional to intensity of
the stressful stimuli

116. THE ADRENAL SEX
HORMONES
Adrenal androgen “Dehydroepiandrosterone” and
androstenedione

117. The adrenal sex hormones
Development and
maintenance of
female sex drive
Have no
masculinizing
effect in their
normal amount

118. The adrenal
sex hormones ACTH controls
adrenal androgen
secretion
Adrenal androgens
feedback outside
the hypothalamus
pituitary adrenal
cortex loop
Instead of inhibiting
CRH, it inhibits
gonadotropin
releasing hormone,
just as testicular
androgen do
Adrenal androgen
secretion undergoes
a marked surge, at
the time of puberty,
and peaks between
the ages 25 and

119. Disorders of the
adrenal cortex
Is most commonly caused by autoimmune destruction of the adrenal cortex by erroneous
production of adrenal cortex – attacking antibodies
Characterized by deficiency of all adrenocortical hormones and hyper- pigmentation
Pituitary or hypothalamic abnormality
Does not exhibit hyper-pigmentation
Aldosterone levels are normal
Decreased sodium
Decrease ECF volume
Hyperkalemia → disturbs cardiac rhythm and metabolic acidosis
Patient dies in shock if untreated
Disruption in glucose concentration

120. Disorders of
the adrenal
cortex
Reduction in metabolism of fats and proteins
Decreased resistance to different types of stress
Pigmentation of mucous membranes, pressure areas of
skin areola & nipple due to increased ACTH secretion
Loss of pubic and axillary hair in females
Anemia

121. NB: Addisonian
crisis
Primary hyperaldosteronism
Caused by over activity of the zona
glomerulosa as a result of hypersecreting
adrenal tumor
Caused by inappropriately high activity of the
renin – angiotensin system
The symptoms of both are related to
exaggerated effects of aldosterone

122. NB: ADDISONIAN
CRISIS
High blood pressure

123. NB: Addisonian
crisis
Metabolic alkalosis , decreases the plasma
Ca++
Overstimulation of the adrenal cortex by
excessive amount of CRH or ACTH
Adrenal tumors that uncontrollably secrete
cortisol independent of ACTH
ACTH secreting tumors located in places other
than the pituitary, most commonly in the lung
Administration of pharmacological doses of
glucocorticoids

124. NB: Addisonian
crisis
↑ Cortisol and androgen levels
↑ ACTH , ↓ ACTH
Hyperglycemia, glucosuria
Central obesity , round face supraclavicular fat
↑ Protein catabolism leads to muscle wasting and fatigue
Poor wound healing and easy bruisability
Hypertension
Osteoporosis
The protein poor thin skin of the abdomen becomes over overstretched by the excessive
underlying fat deposits forming irregular reddish purple linear streaks
Virilization of women

125. Adrenogenital syndrome
Male pattern of
body hair
Deepening of the
voice and more
muscular arms
and legs

126. Adrenogenital syndrome
The breast become smaller, and menstruation may cease , and
sterility occur
◦ Female infants born with a male – type external genitalia

127. ADRENOGENITAL
SYNDROME
Pre-pubertal males: Precocious pseudo-puberty

128. Adrenogenita
l syndrome
Over activity of adrenal androgens in adult
males has no apparent effect
The adrenogenital syndrome is most
commonly caused by enzymatic defect in
the cortisol steroidogenic pathway
The decline in cortisol secretion removes –
ve feedback effect on the hypothalamus
and anterior pituitary →↑ CRH and ACTH
→↑ androgen pathway

129. Adrenal
medulla
The adrenal medulla forms about 20% of the
adrenal gland
It is a modified postganglionic sympathetic
neuron where the neurons have lost their
axons and become secretory cells
Controlled by preganglionic sympathetic
innervation
Secretes epinephrine and norepinephrine

130. Adrenal medulla
Hormones are secreted and stored in the adrenal medulla and released in response to
appropriate stimuli by exocytosis
◦ Epinephrine is primarily a hormone produced by the adrenal medulla, whereas
norepinephrine is also a neurotransmitter of major importance in sympathetic nervous
system
◦ Adrenomedullary hormones are not essential for life, but virtually all organs in the body
are affected by these catecholamines
◦ The effects of epinephrine and norepinephrine are brought about by actions on two
classes of and β adrenergic receptors
◦ Epinephrine and norepinephrine exert similar effects in many tissues, with epinephrine
generally reinforcing sympathetic nervous activity
Both hormones increase the force and rate of contraction via β1 receptors

131. Adrenal
medulla
Both hormones also increase myocardial excitability
Increase arterial blood pressure
Norepinephrine produces vasoconstriction in almost all organs via a1
Epinephrine promotes vasodilation of the blood vessels that supply skeletal
muscle and the heart through β2 receptor activation
Epinephrine constricts blood vessels which have α-adrenergic receptors in their
smooth muscle
A central role of epinephrine is to increase the availability of metabolites for the
intensive physical activity involved in the acute stress situation described
The release of glucose from the liver to the blood is increased by epinephrine in
several ways: it increases glycogenolysis, and stimulates gluconeogenesis

132. Adrenal
medulla
Epinephrine stimulates glycogenolysis in skeletal
muscles, leading to the formation of lactic acid
In pancreatic beta cells, epinephrine inhibits the
production of insulin, and stimulates glucagon
In adipose tissue, epinephrine stimulates the lipolysis
Epinephrine increases the overall metabolic rate
Catecholamines affect the central nervous system to
promote a state of arousal and increased CNS alertness

133. Endocrine control of
calcium metabolism
About 99% of the Ca 2+ in the body is in crystalline
form within the skeleton and teeth
◦ About 0.9% is found intra-cellular within the
soft tissues
◦ Less than 0.1 % is present in the ECF
◦ Half of the ECF Ca2+ either is bound to
plasma proteins and therefore restricted to
the plasma or is complexed with PO4 3
◦ The other half of the ECF Ca2+ is freely
diffusible and can readily pass from the
plasma into the interstitial fluid and interact
with the cells

134. Endocrine control of
calcium metabolism
Neuromuscular excitability

135. Endocrine control of calcium metabolism
Excitation-
contraction
coupling in cardiac
and smooth muscle
Stimulus-secretion
coupling

136. Endocrine control of
calcium metabolism
Maintenance of tight junctions
between cells

137. Endocrine control of
calcium metabolism
Clotting of Blood

138. Endocrine
control of
calcium
metabolism
Calcium homeostasis: Involves the immediate
adjustments required to maintain constant free
plasma Ca2+ concentration on a minute
Calcium balance: Involves the more slowly
responding adjustments required to maintain a
constant total amount of Ca2+ in the body
The principal regulator of Ca2+ metabolism is
the parathyroid hormone
Vitamin D also contributes in important ways
to Ca2+ balance, and the third hormone is
calcitonin

139. Parathyroid
gland
Location: Four glands imbedded on
posterior surface of Thyroid
Secretes: Parathyroid hormone
Function: Calcium regulation
Produce parathyroid hormone
Increases blood concentration of Ca2+

140. Parathyroid
hormone The primary hormone
controlling Ca2+ is
parathyroid hormone,
PTH is essential for
life
PTH raises the Ca++
concentration in the
plasma
This hormone also
lowers PO4 3- in the
blood
There is an inverse
relationship between
Ca++ & PO4 3- levels
in the blood plasma;
the product of their
two concentrations
must be constant

141. Mechanism
of action of
PTH
BONE
PTH uses bone as a bank from which it withdraws Ca2+ as needed to maintain
plasma Ca2+ level
PTH has two major effects on the bone that raise plasma Ca2+ concentration
PTH quickly releases Ca++ from the small labile pool in bones
It stimulates the transfer of Ca2+ from the bone fluid across the osteocytic-
osteoblastic bone membrane into the plasma by means of PTH activated Ca2+
pumps located in the osteocytic osteoblastic bone membrane
Ca2+ is quickly replaced in this area from mineralized bone

142. Second
Under conditions of chronic hypocalcemia
PTH influences the slow exchange of Ca2+
between bone itself and ECF by promoting
actual localized dissolution of bone
It stimulates osteoclast to eat up bone,
increasing the formation of more osteoclasts,
and transiently inhibiting the bone forming
activity of osteoblast
Prolonged excess PTH secretion over months
or years eventually lead to the formation of
cavities throughout the bone, that are filled
with very large, overstuffed osteoclasts
KIDNEY
PTH increases reabsorption of calcium &
reduces reabsorption of phosphate
Net effect of its action is increased calcium &
reduced phosphate in plasma
It enhances the activation of vitamin D by the
kidney

143. Second
INTESTINE
◦ PTH indirectly increases both Ca2+ and PO43- absorption from the
small intestine by helping active vitamin D
◦ The PTH induced removal of extra PO43- from the body fluids is
essential for preventing reprecipitation of Ca2+ freed from bone

144. The solubility product plasma
concentration of Ca2+ X plasma
concentration of PO 3- constant.

145. A rise of their concentrations will raise this value above the
solubility product and results in the precipitation of the salt
When plasma PO43- level rises, some plasma Ca2+ is forced back
into bone through hydroxyapatite crystal formation, reducing
plasma Ca level and keeping constant the calcium phosphate
product

146. A rise of their concentrations will raise this
value above the solubility product and results
in the precipitation of the salt
PTH secretion is increased in response
to a fall in plasma Ca2+ concentration
and decreased by a rise in plasma
Ca2+ levels
A rise in PO43- will decrease
extracellular Ca2+ causing an increase
in PTH
1, 25 2 D3 inhibits the formation of
PTH and so decreases its secretion

147. Calcitonin Calcitonin is a polypeptide hormone secreted by the
parafollicular or “C” cells of the thyroid gland
It is released in response to high plasma calcium
Calcitonin acts on bone osteoclasts to reduce bone
resorption
Net result of its action is a decline in plasma calcium &
phosphate
It is not essential for maintaining either Ca2+ homeostasis
or balance, it is important in extreme hypercalcemia

148. Calcitonin First: On short term basis calcitonin decreases Ca2+ movement
from the bone fluid into the plasma
Second: On long term basis calcitonin decreases bone
resorption by inhibiting the activity of osteoclasts
It stimulates secretion of Ca2+ and PO43- in urine
It inhibits 1a hydroxylase activity of the proximal tubules
Increase plasma Ca2+ stimulates calcitonin secretion and a fall
in plasma Ca2+ inhibits calcitonin secretion
Calcitonin plays a role in protecting skeletal integrity when
there is a large Ca2+ demand as in pregnancy or breast feeding

149. Vitamin D
Food
UV light mediated cholesterol
metabolism

150. Vitamin D
It must be activated by two sequential
biochemical alterations that involve
the addition of two hydroxyl groups
The first of these reactions occurs in
the liver and the second in the kidneys

151. VITAMIN D3
Increase Ca2+ and PO43-
absorption in the intestine

152. Vitamin D3
It stimulates Ca2+
and PO43-
reabsorption in
the kidney
Increases the
responsiveness of
bone to PTH

153. Calcium
Disorders Hyperparathyroidism: can occur by excess PTH secretion
The affected individual can be asymptomatic or symptoms can be severed
Hypercalcemia reduces the excitability of muscle and nervous tissue, leading
to muscle weakness, decreased alertness, poor memory and depression
Other effects are the thinning of bones, development of kidney stones and
digestive disorders such as peptic ulcers, nausea and constipation
Hyperparathyroidism has been called a disease of bones, stones and
abdominal groans
PTH hyposecretion leads to hypocalcemia and hyperphosphatemia

154. Calcium Disorders
Causes: Iatrogenic or
autoimmune attack against
the parathyroid glands
Tetany is a clinical state of
increased neuro-muscular
excitability caused by a
slight decrease in the
plasma level of ionized
calcium
In complete absence of PTH:
Death results within a few
days, usually because of
asphyxiation caused by
hypocalcemic spasm of
respiratory muscles
A deficiency of vitamin D
decreases intestinal
absorption of calcium