1. 1
The Endocrine System

2. 2
Outline
• Types of Regulatory Molecules
• Endocrine Glands and Hormones
• Paracrine Regulation
• Hormones That Enter Cells
• Hormones That Do Not Enter Cells
• Posterior and Anterior Pituitary Gland
• Thyroid and Parathyroid Glands
• Adrenal Glands
• Other Endocrine Glands

3. 3
SIGNALING AGENTS & FACTORS
Neurotransmitters
Peptides
Oxygen-based molecules, e.g., NO
Prostanoids
Hormones
Cytokines ( some are Chemokines)
Extracellular-matrix molecules
Nutrients & metabolites
Mechanical stimuli, e.g., fluid shear
Cell-surface glycoproteins
Hormones from endocrine
cells & organs are part of a
much larger picture of the
outside controls on cells
Heat, osmolarity, exogenous chemicals, etc
ENDOCRINE

4. 4
Types of Regulatory Molecules
• Hormone – A regulatory chemical secreted into the
blood by an endocrine gland, or an organ
exhibiting endocrine function.
• Target Cells respond to hormone
– Neurohormone – A chemical messenger
secreted by neuron into the blood rather than
the synaptic cleft.
• Paracrine - regulatory molecules work without
being transmitted by the blood – not endocrine
• Pheromone - communication messengers

5. 5
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Axon
Neurotransmitter
Endocrine gland
Paracrine
regulator
Receptor
proteins
Hormone
carried
by blood
Target cell

6. 6
Endocrine Glands and Hormones
• Hormones secreted by the endocrine glands belong to four
chemical categories:
– Polypeptides - short chains of amino acids less than
100 amino acids (insulin & ADH)
– Glycoproteins- longer than100 A.A. with carbs (FSH
and LH)
– Amines - Amines – A.A. derived from tyrosine and
tryptophan – epinephrine and norepinephrine and
melatonin
– Steroids - lipids derived from cholesterol

sex steroids - testosterone, estadiol, progesterone,
and cortisol – secreted by testes, ovaries, placenta
and adrenal cortex

Corticosteroids - adrenal cortex cortisol and
aldosterone (regulates glucose and salt balance)
– All hormones can be categorized as lipophilic (fat
soluble) or hydrophilic (water soluble).

7. 7
Endocrine Glands and Hormones
• Neural and endocrine interactions
– Endocrine system also interacts and cooperates
with the nervous system to regulate the activities
of the other organ systems of the body.
– Secretory activity of many endocrine glands
controlled by nervous system like

Adrenal medulla, posterior pituitary, and
pineal gland

major site for neural regulation is the brain’s
regulation of the anterior pituitary by the
hypothalmus
However many are not under neural control

8. 8
Human Endocrine System
major glands

9. 9
cvlAl
re
u
o
- - - - - - - diaphragm
Parathyroids
Adrenal
cortex
Thyroid
Pituitary
anterior
Pancreas
Gonads
ENDOCRINE ORGANS I

10. 10
[ non-epithelial origin ]
cvlAl
re
uo
- - - - - - - diaphragm
Parathyroids
Adrenal cortex
Thyroid
Pituitary
anterior
Pancreas
Gonads
ENDOCRINE ORGANS II
[Pineal]
[Heart]
[Adrenal medulla]
[Kidney]
[Placenta]
Plus neuroendocrine cells
developed within mature
gut, airway, etc epithelia
[Pituitary, posterior & Brain]
[Adipose
tissue]

11. 11
TYPICAL ENDOCRINE GLAND - Context
hormone
release
vessels
Clumps of endocrine cells
blood
control
Capillary diffusion
TARGET ORGAN
Target cells,
with receptors
for binding
12
transport3
4 5
Target cells’
response
6
Feedback

12. 12
GLAND(S) WHERE CELL TYPES HORMONES SPECIAL
Thyroid Neck
Follicular cells
C cells
Thyronine
Calcitonin
Follicles
for storage
Parathyroid Neck Chief cells Parathormone
/PTH
Small
Adrenal
medulla
Over
kidney
Chromaffin
cells
Epinephrine
Norepinephrine
Nerve
fibers
Adrenal
cortex
Over
kidney
Zona glomerulosa
Zona fasciculata
Zona reticularis
Mineralocorticoids
Glucocorticoids
Sex steroids
Pineal Brain’s
center
Pinealocytes Melatonin Connected
for light
drive
Zones
ENDOCRINE ORGANS I

13. 13
GLAND(S) WHERE CELL TYPES HORMONES SPECIAL
Pituitary
posterior
Axons of PV &
SO hypothal.
neurons
Oxytocin
Vasopressin
/ADH
Extension
of brain
Pancreas Left
upper
quad
Beta, Alpha,
Delta, PP cells
Insulin Glucagon
Somatostatin
Pancr Peptide
Gonads Pelvic/
Scrotal
Granulosa, Theca
Lutein, & Leydig
Sex steroids
Inhibin
Placenta Uterus Syncytiotrophoblast Female: for amplified
hormonal responses
Female:
cyclic
Pituitary
anterior
Below
brain
MTs STs GTs
THs CTs
Blood drains
hypothal.-
pituitary for
control
Prolactin GH
LH FSH TSH
ACTH
Below
brain
Islets
+Pituicytes
s
ENDOCRINE ORGANS II

14. 14
Paracrine Regulation
• Signaling between cells - Local effect and
short-lived occurs in many organs
• Regulatory molecules
– cytokines - regulate different cells of the
immune system
– growth factors - promote growth and cell
division in specific organs – stimulate cell
division at target cells

15. 15
Paracrine Regulation
• Prostaglandins – most diverse group of paracrine regulators
• participate in regulation of:
– immune system – inflammation, pain and fever
– reproductive system – reproductive function ovulation,
labor,
– digestive system – inhibit gastric secretions, incrfease
motility and fluid absorption
– respiratory system - blood vessels constriction and dilation
in lungs
– circulatory system - blood platelets in blood clotting
– urinary system - renal blood flow vasodilation increasing
urine excretion
• Prostaglandin synthesis inhibited by aspirin.
– nonsteroidal anti-inflammatory drug

Ibuprofen

Work to inhibit inflammation and pain by inhibiting
enzyme necessary to produce prostaglandins –
(cyclooxygenase -2)

16. 16
Hormones That Enter Cells
• Lipophilic hormones pass through the target
cell’s plasma membrane and bind to
intracellular receptor proteins.
– hormone receptor complex then binds to
specific regions of DNA

activate genes and regulate target cells

17. 17
Steroid Hormone Action

18. 18
Hormones That Do Not Enter Cells
• Hormones that are too large or too polar to
cross plasma membranes include all of the
peptide and glycoprotein hormones, as well
as catecholamine hormones epinephrine
and norepinephrine.
– bind to receptor proteins located on the
outer surface of the plasma membrane

cyclic AMP second-messenger system
 IP3/CA++
second-messenger system

19. 19
Action of Epinephrine on a Liver Cell
1. Epinephrine is lipophobic and
needs to bind to specific receptor
proteins on cell surface.
2. Acting through intermediary G
proteins the hormone bound
receptor activates the enzyme
adenenylyl cyclase which converts
ATP to cAMP
3. Cyclic AMP performs as a
2ndary messenger and activates
protein kinase-A an enzyme that
was previously inactive
4. Protein kinase–A
phosphorylates and activates the
enzyme phosphorylase which
catalyses the hydrolysis of glycogen
into glucose.

20. 20
IP3/CA++
Second-Messenger System
1. The hormone epinephrine
binds to specific receptor
proteins on the cell surface.
2. Acting through G- proteins,
the hormone-bound receptor
activates the enzyme
phospholipase C, which converts
membrane phospholipids into
inositol triphosphate (IP3)
3. IP3 diffuses thru the cytoplasm
and binds to receptors on the
endoplasmic reticulum
4. The binding of IP3 to the
receptor stimulates the
endoplasmic reticulum to release
Ca++ into the cytoplasm
5. Some of the released Ca++ binds to the receptor protein called calmodulin
6. The Ca++/Calmodulin complex activates other intracellular proteins – producing the
horomone effects

21. 21
Primary endocrine organs
• Hypothalamus and pituitary gland secrete hormones and
regulate other endocrine organs. They are the main
regulatory organs of the endocrine system.

22. 22
Hypothalamus
• Located below the
thalamus and above
the pituitary gland
(=epiphysis)
• Regulates the
pituitary gland
secretions through
two different
mechanisms

23. 23
Hypothalamus - neurohypophysis
• 1- Neurons, receiving
information from
receptors, fire APs
which travel down to
the post pituitary gland
and stimulate the
release of stored
neurohormones –
Oxytocin (OT) and anti-
diuretic hormone
(ADH)

24. 24
Hormones of the posterior pituitary
Regulation Hormone Target organ Action Pathology
Reflex Oxytocin - Uterus (smooth
muscle)
- breast tubules
(smooth muscles)
-labor and delivery
- milk-let down
--
--
Reflex (osmoreceptor) ADH
(vasopressin)
- DCT in kidney
tubules
- promote H2O
reabsorption
- not enough: diabetes
insipidus
- too much: ↑ BP?

25. 25
Hypothalamus – adenohypophysis
• 2- Upon stimulation, secretory
cells located in the
hypothalamus secrete
“releasing” hormones which
travel down a capillary bed
toward the anterior pituitary
gland (adenopituitary). Each
type of releasing hormones will
stimulate the secretion and
release of a pituitary hormone.
• Hormones which control the
secretion of other hormones are
tropic hormones (found in
hypothalamus and pituitary
gland

26. 26Figure 6.5
Hormones of the hypothalamus and anterior
pituitary gland

27. 27Figure 6.8
Anterior pituitary
Regulation Hormone Target organ Action Pathology
GHRH and GHIH Growth hormone (GH) Many cells
(bones..)
Stimulate cell
growth and
cell division
- not enough:
children 
pituitary dwarfism
too much:
gigantism
(children) –
acromegaly (adult)
PRH - PIH Prolactin (PL) Breast secretory
cells
- milk
secretion
--
TRH Thyroid stimulating
hormone (TSH)
Thyroid gland - promote
thyroid gland
secretion (T3
and T4)
- not enough:
hypothyroidism
(cretinism in
children)
- too much:
hyperthyroidism
CRH Adrenocorticotropic
hormone (ACTH)
Adrenal cortex (3
layers)
- stimulates
secretion of
adrenal cortex
- not enough:
Addison's disease
- too much:
Cushing syndrome
GnRH Gonadotropin
- Follicle stimulating
hormone (FSH)
- Luteinizing hormone
(LH)
Stimulate gamete
maturation
Stimulate
gonadal gland
secretion and
gamete
formation
- infertility

28. 28
Figure 23-17
Same Individual with Acromegaly (evolution over 20
years)

29. 29Figure 6.6
Mechanism of control

30. 30
HYPOPHYSIS/ Pituitary gland
Pituitary stalk
Posterior lobe
Hypoth alamus
Anterior lobe
Dura
IIIrd Ve
Intermediatelobe

31. 31
Pars nervosa
Infundibular
process
Pars intermedia
PITUITARY SUB-DIVISIONS
Hypothalamic
SO & PV nuclei
Hypothalamic
median
eminence
ADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem
neural part of stalk
1
3
2
1
2
3

32. 32
Unlike some other endocrine cells, those of
the anterior pituitary separate their supplying a
hormone from the detection of the need for the
hormone.
The sensitivity to need is performed by
hypothalamic neurons, which can coordinate
requirements for several hormones with drives,
and events outside the person.
Anterior-pituitary cells & hormones
The system also allows for control by inhibitory
factors, as well as + driving hormone-releasing
factors

33. 33
HYPOTHALAMO-HYPOPHYSEAL Portal flow
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe
capillaries
Dura
Hypothalamic
capillary bed
Neurosecretory neurons
Veins
1
2
3
4
5
A portal flow takes venous
blood drained from one organ
and uses it as a supply to
another organ, e.g., gut to liver

34. 34
HYPOTHALAMO-HYPOPHYSEAL Portal flow
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe
capillaries
Hypothalamic
capillary bed
Neurosecretory neurons
Veins
1
2
3
4
5
Portal flow carries factors
from hypothalamic neurons
to pituitary anterior-lobe cells
E.g.,TH-RF
from neuron
causes
Thyrotroph
to release
TSH

35. 35
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe
capillaries
Hypothalamic
capillary bed
Neurosecretory
neurons
Veins
1
2
3
4
5
Mammotrophs MTs
Somatotrophs STs
Gonadotrophs GTs
Thyrotrophs THs
Corticotrophs CTs
Blood drains hypothalamus-pituitary for control by RFs, etc
Prolactin PRL
Growth hormone GH
Luteinizing hormone LH
Follicle-stimulating
hormone FSH
Thyroid-stimulating
hormone TSH
Adrenocorticotrophic
hormone ACTH
Anterior-pituitary cells & hormones

36. 36
Mammotrophs MTs
Somatotrophs STs
Gonadotrophs GTs
Thyrotrophs THs
Corticotrophs CTs
Blood drains hypothalamus-
pituitary for control by RFs, etc
Prolactin PRL
Growth hormone GH
Luteinizing hormone LH/ICSH
Follicle-stimulating hormone
FSH
Thyroid-stimulating hormone
TSH
Adrenocorticotrophic
hormone ACTH cleaved from
pro-opio-melanonocortin/ POMC
Anterior-pituitary cells & hormones
Acidophil
Basophil

37. 37
Anterior-pituitary cells 2
Mammotrophs MTs
Somatotrophs STs
Gonadotrophs GTs
Thyrotrophs THs
Corticotrophs CTs
Prolactin PRL
Growth hormone GH
Luteinizing hormone LH
FSH
TSH
ACTH
Acidophil Basophil Chromophobe
Chromophobes stain weakly, in comparison to CHROMOPHILS -
Acidophils & Basophils
Folliculo-Stellate cells lie amongst the glandular
cells; doing what?

38. 38
Anterior-pituitary cells 3
Corticotrophs CTs ACTH
but by selective enzymatic cleavage of a larger 32kDa
precursor - pro-opiomelanocortin, also made in the
hypothalamus and elsewhere, and there serving to
provide other hormones & neurotransmitters
Pro-opiomelanocortin
ACTH
Pro-ACTH β-LPH
β-Endorphin
β-
MSH
SP
simplified
POMC ~ Pro-opiomelanocortin

39. 39
Anterior-pituitary cells 4
Selective enzymatic cleavage of the precursor - pro-
opiomelanocortin, provides other hormones & transmitters
ACT
H
β-Endorphin
Pro-opiomelanocortinSP
NT 1-76
β-LPHACTH
β-LPHACTH
γ-LPH
NT 1-49
JP
γ -MSH α-MSH β-MSH
elaborate
MSH ~ Melanocyte-stimulating hormone
NT ~ amino-terminal peptides
LPH ~ Lipotropic hormone
Pro-hormone convertase 1
Pro-hormone convertase 1
Pro−γ -MSH
Pro−γ -MSH
After Reudelhuber
TL. J Clin Invest
2003;111:1115-1116

40. 40
NEUROHYPOPHYSIS
Pars nervosa
Hypothalamic SO & PV nuclei
Supraoptic & Paraventricular nuclei
Hypothalamus 1
2
3
Inferior arteries
Veins
Release of hormone is
separated from production
*
*
*
*
Neural stalk
Optic
chiasm

41. 41
NEUROHYPOPHYSIS
Pars nervosa
Hypothalamic SO & PV nuclei
Supraoptic & Paraventricular nuclei
Hypothalamus 1
2
3
Inferior arteries
Veins
*
*
Neural stalk
Optic
chiasm
Note - the supraoptic nucleus is
above the optic nerve & chiasm, but
closer to the chiasm is the small
suprachiasmatic nucleus (relaying
the darkness stimulus indirectly to
the pineal gland).

42. 42
NEUROHYPOPHYSIS
Pars nervosa axons, terminals,
pituicytes & capillaries
Hypothalamic SO & PV nucleiHypothalamus
Infundibular stem
neural part of stalk - axons & glia
1
2
3
Neurosecretory neurons producing
oxytocin & vasopressin/ADH
Inferior arteries
Veins
Release of hormone is
separated from production
* *
*
*

43. 43
NEUROHYPOPHYSIS
Hypothalamic SO & PV nucleiHypothalamus
Neurosecretory neurons producing
oxytocin & vasopressin/ADH
Inferior arteries
Veins
Hormone travels down the
axon bound to the carrier
protein - neurophysin, from
which it is cleaved for release
*
*

44. 44
SUCKLING REFLEX
Hypothalamic SO & PV neuron activation
Hypothalamus
*
BREAST
Myoepithelial-cell
contraction
Sensory response
Oxytocin release
Stimulus1
2
3
4
56
7 Milk ejectionVascular transfer

45. 45
PITUITARY Mid-sagittal section of 1-m embryo
STOMODEUM
PHARYNGEAL ARCHES
PITUITARY
RATHKE’S POUCH
starting in oral ectoderm
BRAIN
I
II

46. 46
PITUITARY DEVELOPMENT II
Neural-tube diencephalic ectoderm
Oral-pharyngeal lining ectoderm
IIIrd Ve
Rathke’s pouch
Pars tuberalis
Pars distalis
Pars intermedia
Pars nervosa
Infundibular stem
Hypothalamus
ADENOHYPOPHYSIS
NEUROHYPOPHYSIS

47. 47
PITUITARY DEVELOPMENT II
Pars tuberalis
Pars distalis
Pars intermedia
Pars nervosa
Infundibular stem
Hypothalamus
Pars nervosa
Infundibular
process
Pars intermedia
Hypothalamic
SO & PV nuclei
Hypothalamic
median
eminence
ADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem
neural part of stalk1
3
2
1
2
3
Cysts
Cysts in Pars intermedia - remnants
of Rathke’s pouch lumen?
Rathke’s pouch lumen

48. 48
Pars nervosa/
Infundibular process
Pars intermedia
Hypothalamic
SO & PV nuclei
Hypothalamic
median eminence
ADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem/
neural part of stalk1
3
2
1
2
3
Cysts
Cysts in Pars intermedia - remnants
of Rathke’s pouch lumen?

49. 49
Posterior Pituitary Gland
• Pituitary gland hangs by a stalk from the
hypothalamus of the brain.
– anterior pituitary - appears glandular
– posterior pituitary - appears fibrous
• Neurons produce antidiuretic hormone
(ADH) and oxytocin.
– stored in, and released from, the posterior
pituitary gland in response to neural
stimulation from the hypothalamus

50. 50
Effects of ADH

51. 51
Anterior Pituitary Gland
• Develops from a pouch of epithelial tissue that pinches off the
roof of the embryo’s mouth.
– produces the hormones it secretes:

growth hormone (GH) stimulates muscles and bones to
grow

adrenocorticotropic hormone (ACTH) regulates glucose
homeostasis

thyroid-stimulating hormone (TSH) stimulates the
production of thyroxin by thyroid gland

luteinizing hormone (LH) ovulation and testosterone
production in testes

follicle-stimulating hormone (FSH) develops ovarian
follicle and sperm in males

prolactin (PRL) stimulates mammary glands to produce
milk

melanocyte-stimulating hormone (MSH) synthesis and
dispersion of melanin pigment

52. 52
Major Pituitary Gland Hormones

53. 53
Anterior Pituitary Gland
• Hypothalamic control of anterior pituitary
gland secretion
– Neurons in the hypothalamus secrete
releasing hormones and inhibiting
hormones into blood capillaries at the base
of the hypothalamus.

Each hormone delivered by
hypothalamohypophysial portal system
regulates secretion or inhibition of a
specific anterior pituitary hormone.

54. 54
Neurons in the hypothalamus secretes hormones that are carried by short
blood vessels directly to the ant. Pituitary gland, where they either stimulate
or inhibit the secretions of the ant pituitary hormones
Cell body
Axons to
primary
capillaries
Primary
capillaries
Pituitary stalk
Posterior pituitary
Anterior pituitary
Secondary
capillaries
Portal
venules

55. 55
Anterior Pituitary Gland
• Negative feedback inhibition acts to maintain
relatively constant levels of the target cell
hormone.
– Positive feedback cannot maintain
constancy of the internal environment.

56. 56
Negative Feedback Inhibition
Hormones secreted by some endocrine glands feed back to inhibit
the secretion of hypothalamic releasing hormones and anterior
pituitary hormones

57. 57
Thyroid and Parathyroid Glands
• Thyroid gland
– Shaped like a shield and lies just below the
Adam’s apple in the front of the neck.

Thyroxine helps set basal metabolic rate
by stimulating the rate of cell respiration.

In children, thyroid hormones also
promote growth and stimulate maturation
of the central nervous system.

unique function in amphibians -
metamorphosis from larvae into adults

58. 58
Regulation of Thyroxine Secretion

59. 59
Thyroid and Parathyroid Glands
• Parathyroid gland and calcium homeostasis
– four small glands attached to the thyroid

produces parathyroid hormone (PTH)

one of only two hormones in humans
that are absolutely essential for survival

stimulates osteoclasts in bone to
dissolve calcium phosphate crystals
and release Ca++
into the blood

60. 60
Regulation of Blood Calcium Levels

61. 61
Calcium Metabolism:
Figure 23-20: Calcium balance in the body

62. 62Figure 19.20

63. 63
THYROID GLAND
Follicular cells
simple cuboidal
epithelium
Colloid / Thyroglobulin
glycoprotein = PAS+
Follicles for storage
C cells/ Parafollicular cells
Capillaries
In the section, the follicles do not hold their spherical shape this
well, and the colloid displays knife chatters and variable staining

64. 64
THYROID GLAND: Physiological variablity
Follicular cells high
cuboidal when very active;
squamous when inactive
Colloid / Thyroglobulin
less in active state,
excessive in goitre
Follicles - size
varies inversely with
activity
C cells/ Parafollicular
cells for calcitonin
Capillaries

65. 65
GOLGI
Amino acids
Sugars
Iodine
Thyroglobulin
Endocytosis
Cleavage
Release of hormones
T3 & T4
Synthesis &
iodination of
thyroglobulin
THYROID FOLLICULAR CELL
TSH

66. 66
Goiter
• Both hypo and hyperthyroidism can have
goiter as a symptom
• Goiter is a swelling of the neck due to
hypertrophy of the thyroid gland
• How can one explain that?

67. 67
Goiter in hypothyroidism
• Most often due to a lack of dietary
iodine
• The thyroid hormone is unable to
synthesize a functional thyroid
hormone (T3 and T4)
• The person express symptoms of
hypothyroidism
• The nonfunctional T3/T4 cannot
promote a negative feedback on
TRH and TSH

 the hypotalamus and pituitary
gland increase their secretions 
the thyroid gland is stimulated to
secrete more T3 and T4 …
• In children, the lack of functional
T3/T4 result in cretinism, a form a
mental retardation

68. 68
Goiter in hyperthyroidism
• The cells secreting TRH or TSH
on the hypothalamus and
pituitary gland (respectively)
have become abnormal and no
longer are sensitive to the
negative feedback  they
continue to secrete TRH or TSH
 continuous stimulation of the
thyroid gland with excess thyroid
hormones being formed

 symptoms of hyperthyroidism

69. 69
PARATHYROID GLAND
Oxyphil cells
Chief cells
Characteristic is the
lack of obvious general
structural features
Small, pale, resemble
lymphocytes, but
have more cytoplasm
Larger, eosinophilic,
darker nuclei,
packed with
mitochondria

70. 70
PARATHYROID GLAND
OXYPHIL CELLS
CHIEF CELLS
have membrane
calcium sensors to
respond to low Ca2+
by releasing
parathyroid
hormone /PTH. PTH
stimulates
osteoclasts to
release Ca2+
from
bone & has
conserving renal
effects
derivatives of Chief cells

71. 71
Osteoclast
Ruffled border agitating
released enzymes & acid
Eaten-out hole is
a Howship’s
lacuna
BONE REMODELING
Osteoclasts as a team eating
out a resorption tunnel
Sealing ring
of tight
attachment
to bone
BONE
MATRIX
BONE

72. 72
ONCOCYTIC CONVERSION
As cuboidal epithelia and glands age, a few of
their epithelial cells lose most of their normal
organelles and fill up with mitochondria.
Mitochondria-rich cells are eosinophilic.
This event results in two classes of cell:
those that are functioning normally and need
many mitochondria - gastric parietal cells, renal
proximal-tubular cells, striated-duct cells, etc; &
non-functional mitochondria-stuffed cells in older
epithelia. These have acquired two names: the
usual - oncocyte, and, as an exception, the
archaic oxyphil cell in the parathyroids. & Hurthle cells
in thyroid
:

73. 73
Adrenal Glands
• Adrenal glands are located above each
kidney.
– Each gland composed of inner portion
(adrenal medulla) and outer layer (adrenal
cortex).
• Adrenal medulla
– receives neural input from axons of
sympathetic division of the autonomic
nervous system, and secretes epinephrine
and norepinephrine in response

74. 74
Adrenal Glands
• Adrenal cortex
– Hormones from adrenal cortex are
collectively referred to as corticosteroids.

Cortisol maintains glucose homeostasis,
and modulates some aspects of the
immune response.

Aldosterone stimulates the kidneys to
reabsorb Na+
and secrete K+
into the
urine.

75. 75
Adrenal Glands

76. 76
Cortex
Medulla
Capsule
Adrenal vein
ADRENAL/SUPRARENAL GLAND
The adrenal embryologically is a composite of the:
medulla derived from ectoder mal neural-crest cells; &
cortex formed from mesoder m next to the mesonephros

77. 77
ADRENAL CORTEX
Cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
]
]
small balls of cells
straight bundles of paler cells
cords of cells in a network
sparse
Stroma of
reticular
fibers &
vessels
Capsule

78. 78
ADRENAL CORTICAL HORMONES
Cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
]
]
makes mineralocorticoids, e.g.,
aldosterone
makes glucocorticoids, e.g., cortisol
makes sex steroids, e.g., androstenedione

79. 79
Zona glomerulosa regulated by
Renin-angiotensin system
Zona fasciculata driven by ACTH
Zona reticularis driven by LH & ACTH
]
]
to make & release mineralocorticoids
to make glucocorticoids
to make sex steroids* & glucocorticoids
Zona-fasciculata steroid-synthesizing cell
Cholesterol droplets
(often dissolved out)
Smooth ER, often tubular
(bag-of-worms visual effect)
Mitochondria with tubular
cristae
dehydroepiandrosterone*

80. 80
Zona glomerulosa
regulated by
Renin-angiotensin
system
mineralocorticoids
glucocorticoids
sex steroids* &
glucocorticoids
]
]
Zona reticularis
driven by LH & ACTH
Zona fasciculata
driven by ACTH

81. 81
Zona-fasciculata steroid-synthesizing cell
Cholesterol droplets
(often dissolved out)
Smooth ER, often tubular
(bag-of-worms visual effect)
Mitochondria with
tubular cristae
Inner mitochondrial
membrane has a P450
enzyme for steroid
biosynthesis

82. 82
Zona glomerulosa ]
JG cells
Renin
Converting
Enzyme
DISTAL
TUBULE
Angiotensinogen
Angiotensin I
Angiotensin II
Aldosterone
Vasoconstriction
Sodium + water
reabsorption (so blood pressure up)
JUXTAGLOMERULAR APPARATUS 6
Outside
kidney
Renin is a protease

83. 83
Aldosterone
Zona glomerulosa
JG cells
Renin
Converting
Enzyme/ ACE
Angiotensinogen
Angiotensin I
Angiotensin II
Vasoconstriction
RENIN-ANGIOTENSIN SYSTEM
DISTAL
TUBULE
Outside
kidney
ACE is in many tissues, and the angiotensin II
receptor is widespread, so that the RA system
is very endocrine in affecting most of the
body, not just vessels, adrenal & kidney

84. 84
ADRENAL MEDULLA
Chromaffin cells
Sympathetic axons
Central vein
Occasional neuron
terminating
mainly on
chromaffin
cells
Chromaffin cells so named, because of chromaffin reaction
- a brown darkening of medulla seen when catecholamines
react with dichromate & other oxidising agents

85. 85
ADRENAL MEDULLA
Chromaffin cells
make epinephrine
& norepinephrine
Sympathetic axons
Central vein
Occasional neuron
terminating
mainly on
chromaffin cells
Epinephrine & norepinephrine are catecholamines stored,
in association with the protein chromogranin, in dense-
cored granules/ vesicles. E & NE augment sympathetic
autonomic nervous-system actions

86. 86
CATECHOLAMINE SYNTHESIS
Chromaffin cells make epinephrine & norepinephrine
TYROSINE
tyrosine hydroxylase
DOPA/Dihydroxyphenylalanine
DOPAMINE
aromatic L-amino acid decarboxylase/AADC
dopamine β-hydroxylase/DBH
NOREPINEPHRINE
EPINEPHRINE/Adrenalin
phenylethanolamine-N-methyltransferase
[rate-limiting?]

87. 87Figure 6.12b

88. 88Figure 21.15

89. 89
Adrenal gland hormones
Regulation Glands Hormones Target
organs
Action Pathology
Reflex Adrenal medulla Epinephrine ANS target
organs
Fight/flight Stress
Blood Pressure Adrenal cortex - Mineralocorticoid =
aldosterone
DCT from renal
tubule
- promote sodium
reabsorption
Not enough"
Addison disease
CRH  ACTH Glucocorticoid =
cortisone
Many cells Mobilize fuels –
stress adaptation
Excess hormone:
Cushing
syndrome
GnRH  GN Estrogen
Testosterone
Sexual organs - Sex organ
maintenance
- Gamete
development
Infertility

90. 90

91. 91
Pancreas
• Located adjacent to the stomach and is
connected to the duodenum by the
pancreatic duct.
– Secretes bicarbonate ions and a variety of
digestive enzymes into small intestine.

β cells of islets of Langerhans secrete
insulin, and α cells secrete glucagon.

antagonistic

Insulin lowers while glucogen
raises blood glucose.

92. 92
PANCREAS
Duodenum
Exocrine acini
digestive enzymes
Lobule
}
Endocrine islet
metabolic hormones
Ducts
alkaline ions
Enteroendocrine cells
hormones

93. 93
Islet of Langerhans
ISLET: Cell types & products
Beta cell - insulin (majority)
Alpha cell - Glucagon
Delta cell - Somatostatin
PP cell - Pancreatic polypeptide
Beta & Alpha cells are directly sensitive to glucose level

94. 94
Antagonistic Actions of Insulin and Glucagon

95. 95
Glucose regulation
• Glucose level controlled by
insulin and glucagon
• Insulin promotes a
decrease in blood glucose
• Glucagon promotes an
increase in blood glucose

96. 96
Glucose regulation

97. 97Figure 3.21
Fate of glucose

98. 98
Diabetes mellitus
• Type I: autoimmune disease  beta cells of
the islets of Langerhans are destroyed by
antibodies
• Type II: The cells become insulin-resistant
 glucose does not enter the cells as
readily

99. 99
Diabetic foot

100. 100
Other Endocrine Glands
• Ovaries and testes
– produce androgen

secondary sexual characteristics
• Pineal gland
– secretes melatonin

regulates biological clocks

101. 101
Other Endocrine Glands
• Molting and metamorphosis in insects
– Hormone secretions influence both
molting and metamorphosis in insects.

Brain hormone stimulates production of
ecdysone (molting hormone).

high levels cause molting to occur

juvenile hormone

high levels prevent transformation to
an adult

102. 102
Other Endocrine Glands
• Endocrine disrupting chemicals
– chemicals that interfere with hormone
function

Any chemical that can bind to receptor
proteins and mimic the effects of the
hormone is called a hormone agonist.

Any chemical that binds to receptor
proteins and has no effect, but blocks
the hormone from binding is a hormone
antagonist.

103. 103
Cerebral
Cortex
Cerebellum
Pineal gland
Brain Stem
Eye & optic
nerve
Central sympathetic
pathways
Suprachiasmatic
nucleus
Thoracic cord
Sympathetic
preganglionic
S Cervical ganglion
Sympathetic
postganglionics
PINEAL ACTIVATION PATHWAY
1
3
4
2
5
7
Darkness increases HIOMT
enzyme to make melatonin HydroxyIndole-O-MethylTransferase
1 7
6

104. 104
Cerebral Cortex
Cerebellum
Pineal gland
Brain Stem
Eye & optic
nerve
Central sympathetic
pathways
Suprachiasmatic
nucleus
Thoracic cord
Sympathetic
preganglionic
S Cervical ganglion
Sympathetic
postganglionics
PINEAL ACTIVATION PATHWAY
1
3
4
2
5
6
1 7
7 melatonin
light off
Melanopsin in retinal ganglion cells
is the photosensitive mediator

105. 105
Cerebral Cortex
Cerebellum
PINEAL GLAND
Brain Stem
Eye & optic
nerve
Central sympathetic
pathways
Suprachiasmatic
nucleus
Thoracic cord
Sympathetic
preganglionic
S Cervical ganglion
Sympathetic
postganglionics
PINEAL ACTIVATION PATHWAY
1
3
4
2
5
7
Darkness increases HIOMT
enzyme to make melatonin HydroxyIndole-O-MethylTransferase
6
melatonin
light off

106. 106
cvlAl
re
uo
- - - - - - -
ENDOCRINE ORGANS II
Plus neuroendocrine cells
developed within mature
gut, airway, etc epithelia
[Kidney]
[Heart] ANF
EPO
Renin
VIP
Gastrin
Secretin, etc
Gonads
[Placenta]
hCG
Estrogen
Progesterone
Sex steroids
[Adipose
tissue]
Leptin

107. 107
ATRIAL HEART & ANF
Atrial myocytes have a well developed Golgi complex and
secretory granules
Reticular fiber
Atrial Natriuretic Factor (ANF) in the granules STIMULATES:
diuresis; sodium excretion (natriuresis); vasorelaxation;
& INHIBITS the Renin-Angiotensin system & aldosterone
secretion

108. 108
Enteroendocrine cell types I
Enteroendocrine cell
small, pale, few; granules
are located basally for
release into the lamina
propria
Entero is misleading because: some cell
types are confined to the stomach; and
peptides & amines are signaling agents in
other epithelia and other systems e.g. brain
G cell - gastrin
S cell - secretin
I cell - cholecystokinin
ECL cell - histamine
D cell (antral) - somatostatin
EC cell - serotonin
A cell - ghrelin

109. 109
Enteroendocrine cell types II
Motilin cell: why not ‘M’ cell? There already is one, involved in immunity
G cell - gastrin
S cell - secretin
I cell - cholecystokinin
ECL cell - histamine
L cell - glucagon-like peptide (GLP-1 & 2)
peptide Y (PYY)
oxyntomodulin
K cell - gastric inhibitory
polypeptide/GIP
N cell - neurotensin
M? cell - motilin
D cell (antral) - somatostatin
Coordinated with extrinsic &
intrinsic neural controls and
interacting amongst
themselves
EC cell - serotonin
A cell - ghrelin

110. 110
EXOCRINE PANCREAS Controls
Duodenum
Exocrine aciniEnteroendocrine cells
Secretin & CCK
digestive enzymes
HCO3
-
ions
RESPONSE
Acid Fats Peptides
STIMULI
CONTROLLER
+ Vagal cholinergic control

111. 111
SOURCES OF ‘GUT’ HORMONES
RECTUM
LIVER
PANCREAS
GALL
BLADDER
STOMACH
SMALL
GUT
LARGE
GUT
Bile
gastrin ghrelin
Duodenum
cholecystokinin motilin
somatostatin
neurotensin
GIP-1
GLP-1&2
Peptide Y
insulin glucagon
PPY somatostatin
secretin
Oxyntomodulin

112. 112
SOURCES OF ‘GUT’ HORMONES
PANCREAS
STOMACH
SMALL GUT
LARGE GUT
gastrin ghrelin
Duodenum cholecystokinin motilin
somatostatin
neurotensin
GIP-1
GLP-1&2 Peptide Y
insulin glucagon PPY somatostatin
secretin
Oxyntomodulin

113. 113
Enteroendocrine cell types III
Immunostaining for the peptide or chromogranin and
fluorescence methods for the amine derivatives now provide
clear identification of the cells, but against a background of the
old silver-based cell nomenclature
A messy story*, because of the various staining reactions of
enteroendocrine cells (particularly with silver methods) based on the
peptide hormones, the associated chromogranin storage protein in
the granules, and any catecholamine, serotonin or histamine
content.
ECL cell - EnteroChromaffin-Like cell

114. 114
Adipocyte hormones & other metabolic players
RECTUM
LARGE
GUT
LIVER
SMALL
GUT
STOMACH
PANCREAS
GALL
BLADDER
E
S
O
P
H
A
G
U
S
MOUTH
APPENDI X
SALIVARY
GLAND
AIRWAY
HYPOTHALAMUS
Appetites
Homeostasis
Emotion
CEREBRAL CORTEX
Cerebellum
Pons
Mid-
brain
Medulla
PITUITARY
TALUS
CALCANEUS Metatarsa
l
FEMUR
Fat cell
Adipocytes
MUSCLE

115. 115
Adipocyte hormones -
LIVER
HYPOTHALAMUS
TALUS
CALCANEUS Metatarsa
l
FEMUR
Fat cell
Adipocytes
MUSCLE
LEPTIN
ADIPONECTIN
for energy balance and
glucose homeostasis

116. 116
Visceral/abdominal fat & type II diabetes, etc
LIVER
HYPOTHALAMUS
TALUS
CALCANEUS Metatarsa
l
FEMUR
Fat cell
Adipocytes
MUSCLE
LEPTIN
ADIPONECTIN
MACROPHAGES(MΦs)
Macrophages accumulate in the stroma of
the fatty tissue, become activated to
release abnormal cytokines , e.g., TNF-
α ,that disrupt many metabolic pathways
so that the visceral adipose tissue is
permanently inflamed and dangerous, e.g.
Adipocyte production of adiponectin falls
Insulin signalling goes bad, etc.

117. 117
TESTIS & LEYDIG CELLS
Peritubular
myoid cells
LEYDIG
INTERSTITIAL
CELLS
Acidophil
Much smooth ER
Lipid droplets
Crystals of Reinke
SERTOLI CELLS
Sperm
layered
SPERMATOGENIC CELLS
{stratified
germinal
epithelium
BASAL LAMINA
SEMINIFEROUS
TUBULE
SEMINIFEROUS
TUBULE

118. 118
HORMONES
PITUITARY
GONADOTROPHS
HYPOTHALAMIC
NEURONS
INTERSTITIAL
CELLS
SEMINIFEROUS
TUBULE
PENIS
SEMINAL
VESICLE
PROSTATE
RETE
TESTIS
TUBULUS
RECTUS EFFERENT
DUCT
EPIDIDYMIS
DUCTUS
DEFERNS
BULBOURETHRAL
GLAND
urethra
Androgens
Courtship
& Coital
behaviors
GnRHFSH
LH
1
2 3
4
5 Secondary
sexual
characters
6
7
Somatic growth &
metabolism