Download The Endocrine System

The Endocrine System
Hypophyseal-Pituitary
Axis
 Site of Neural – Hormonal interaction
 Sets temporal release of hormones
 Responsible for stress reaction of
hormones
The Hypothalamus & the
Pituitary Gland-- Master
Endocrine Glands!
The Hypothalamus:
 Located in the brain,
this region controls
most endocrine
secretions
 Mainly regulatory
hormones are
released here. Most
control the pituitary
gland
The Pituitary Gland
 Descending from the
hypothalamus, this gland
has two halves: anterior
& posterior
 The anterior half
secretes mainly
regulatory hormones
 The posterior half
secretes hormones, but
manufactures none
Hormones secreted by the
Hypothalamus & Anterior
Pituitary Gland
Hypothalamus
Anterior Pituitary
GHRH (GH-releasing)  GH (growth hormone)
SS (somatostatin, GH-inhib)
“
 ACTH (adrenocorticotropic)
CRH (corticotropin-rel)
GnRH (gonadotropin-rel) 
LH (luteinizing
hormone)
“
PRH (PRL-releasing)
PIH (PRL rel-inhibiting)




FSH (follicle-stimulating)
PRL (prolactin)
“
What do these anterior
pituitary hormones do?
Growth Hormone:
 stimulates cells to grow
and divide
 increases amino acid
transport rate and
protein synthesis
 increases fat metabolism
Typically, GH is secreted
during sleep.
GH secretion increases
when malnourished
GH influences bone
growth via
somatomedin:

GH in blood
GH arrives in liver
liver secretes
somatomedin
cartilage divides
bones grow!



Problems with GH
 Too much GH in children leads to
gigantism
 Too much GH in adults leads to
acromegaly
 Too little GH in children leads to
dwarfism
Other Anterior Pituitary
Hormone Functions
ACTH:
LH & FSH:
 works on the cortex of
the adrenal gland,
influencing the release
of cortisol
 stress can increase
CRH secretion which
will increase ACTH
secretion
 negative feedback
when adrenal cortex
hormones in blood
decrease CRH
 LH in females and in males
leads to sex hormone
secretion
 FSH in females causes growth
and development of egg cellcontaining follicles in the
ovary, and causes estrogen
secretion
 FSH in males instigates sperm
production
 both hormones are regulated
by GnRH, which is not
More Anterior Pituitary
Hormone Functions
PRL:
TSH:
 In females, PRL

promotes lactation
 In males, PRL decreases
LH secretion (note that 
too much PRL would
then decrease androgen
levels and cause

sterility)
 Controlled by both PRH 
and PIH
works on thyroid gland to
either cause or inhibit its
secretion of hormones
works on thyroid gland to
affect its growth (too much
TSH leads to a goiter)
negative feedback via
thyroid hormones in blood
stress or cold temperatures
can change TSH secretion
The Posterior Pituitary
Lobe
No hormones are made here. They are
made in the hypothalamus and just
released here.
Two peptide hormones are released from
the posterior pituitary lobe (the
neurohypophysis):
 ADH (antidiuretic hormone or
Function of Posterior
Pituitary Lobe
Hormones
ADH:
OT:
 as an “antidiuretic,” ADH
decreases urine formation by
having kidneys conserve
water
 also can contract smooth
muscle cells, as found in
blood vessels-- this causes an
increase in blood pressure
 ADH release triggered by
osmoreceptors and inhibited
by stretch receptors in blood
 In females, contracts
the uterine wall smooth
muscles
 In females, helps to
eject milk when
lactating
 No known function in
males, although in both
males and females, OT
can have some
antidiuretic effects
Hypothalamus & Anterior
Pituitary
Hypothalamus
GHRH (GH-releasing)
SS (somatostatin, GH-inhib)
CRH (corticotropin-rel)
GnRH (gonadotropin-rel)
Anterior Pituitary
GH (growth hormone)
“
ACTH (adrenocorticotropic)
LH (luteinizing
hormone)
“
PRH (PRL-releasing)
PIH (PRL rel-inhibiting)
FSH (follicle-stimulating)
PRL (prolactin)
“
Your book’s review
diagram:
HPA Basics
 Hypophysis
 Third Ventricle
 GRH, TRH, CRH, GnRH, Dopamine, Somatostatin
 Neurohypophysis
 Derived from Hypophysis
 ADH, Oxytocin
 Adenohypophysis
 Derived from Rathke’s pouch
 ACTH, LH, FSH, TSH, GH, PRL
Pituitary Diseases

Primary Tumors




Metastasis
Empty Sella


Sheehand’s syndrome
Hyperfunction


Surgical, post-Sheehand’s
Hemorrhage


Adenomas
Craniopharyngioma
Prolactin
Insufficiency
The Endocrine Glands and
Their Hormones
 Pituitary Gland
 A marble-sized gland at the base of the brain
 Controlled by the hypothalamus or other neural
mechanisms and therefore the middle man.
 Posterior Lobe
 Antidiuretic hormone: responsible for fluid
retention
 Oxytocin: contraction of the uterus
The Endocrine Glands and
their Hormones
 Pituitary Gland
 Exercise appears to be a strong stimulant
to the hypothalamus for the release of all
anterior pituitary hormones
 Anterior Lobe
 Adrenocorticotropin
 Growth hormone *
 Thyropin
 Follicle-stimulating hormone
 Luteinizing hormone *
 Prolactin
The Endocrine Glands and
Their Hormones
 Thyroid Gland
 Located along the midline of the neck
 Secretes two nonsteroid hormones
 Triiodothyronine (T3)
 Thyroxine (T4)
 Regulates metabolism
 increases protein synthesis
 promotes glycolysis, gluconeogenesis, glucose
uptake
 Calcitonin: calcium metabolism
Thyroid
Thyroid
 Largest Endocrine organ in the body
 Involved in production, storage, and
release of thyroid hormone
 Function influenced by




Central axis (TRH)
Pituitary function (TSH)
Comorbid diseases (Cirrhosis, Graves, etc.)
Environmental factors (iodine intake)
The Thyroid Gland
Structure:
This bilobed gland contains many follicles. A
follicle is a group of cells encircling a lumen. The lumen
contains material called colloid (a glycoprotein) within it. As
hormones are produced by the cells, the hormones are
either released into the colloid or directly into the blood.
There are also extrafollicular hormone-secreting cells,
called C cells. These are found between lumina.
Hormones Produced:
 Thyroxine (T4)
made in follicle
 Triiodotyronine (T3) made in follicle
 Calcitonin
made by C cells
About the Thyroid
Hormones...
T3 and T4:
Calcitonin:
 Function: metabolism
 Function: decrease
regulation (break down
blood calcium levels
carbohydrates and fats,
and blood phosphate
synthesize proteins)
levels (by helping them
get deposited in bone,
 Can only be made by follicular
and by stimulating
cells when iodides are
excretion of them by
available
kidneys)
 Somewhat hydrophobic and
 Controlled by blood
get carried by proteins in the
calcium levels and
blood.
digestive chemicals
 Controlled by anterior pituitary
lobe TSH
Problems with the
Thyroid Gland
Hyperthyroidism:
 high metabolic rate, hyperactivity, sensitivity to heat, protruding
eyes
 Grave’s disease: when hyperthyroidism is due to an
autoimmune problem (TSH is mimicked by autoantibodies)
Hypothyroidism:
 in the adult: low metabolic rate, sensitivity to cold,
sluggishness
 in an infant: cretinism-- stunted growth, mental retardation,
abnormal bone formation
 Hashimoto’s disease: when hypothyroidism is due to an
autoimmune problem (autoantibodies attack and destroy
follicular cells)
Thyroid (cont)

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

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

Regulates basal metabolic rate
Improves cardiac contractility
Increases the gain of catecholamines
Increases bowel motility
Increases speed of muscle contraction
Decreases cholesterol (LDL)
Required for proper fetal neural growth
Thyroid Physiology
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Uptake of Iodine by thyroid
Coupling of Iodine to Thyroglobulin
Storage of MIT / DIT in follicular space
Re-absorption of MIT / DIT
Formation of T3, T4 from MIT / DIT
Release of T3, T4 into serum
Breakdown of T3, T4 with release of
Iodine
Iodine uptake
 Na+/I- symport
protein controls
serum I- uptake
 Based on Na+/K+
antiport potential
 Stimulated by TSH
 Inhibited by
Perchlorate
Secretion of Thyroid
Hormone
 Stimulated by TSH
 Endocytosis of colloid on apical membrane
 Coupling of MIT & DIT residues
 Catalyzed by TPO
 MIT + DIT = T3
 DIT + DIT = T4
 Hydrolysis of Thyroglobulin
 Release of T3, T4
 Release inhibited by Lithium
Thyroid Hormones
Thyroid Hormone
 Majority of circulating hormone is T4


98.5% T4
1.5% T3
 Total Hormone load is influenced by serum
binding proteins (TBP, Albumin, ??)



Thyroid Binding Globulin 70%
Albumin 15%
Transthyretin 10%
 Regulation is based on the free component
of thyroid hormone
Hormone Binding Factors

Increased TBG


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Decreased TBG



High estrogen states (pregnancy, OCP, HRT, Tamoxifen)
Liver disease (early)
Androgens or anabolic steroids
Liver disease (late)
Binding Site Competition



NSAID’s
Furosemide IV
Anticonvulsants (Phenytoin, Carbamazepine)
Hormone Degredation



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T4 is converted to T3 (active) by 5’ deiodinase
T4 can be converted to rT3 (inactive) by 5
deiodinase
T3 is converted to rT2 (inactive)by 5 deiodinase
rT3 is inactive but measured by serum tests
Thyroid Hormone Control
TRH




Produced by Hypothalamus
Release is pulsatile, circadian
Downregulated by T4, T3
Travels through portal venous system to
adenohypophysis
 Stimulates TSH formation
TSH




Produced by Adenohypophysis Thyrotrophs
Upregulated by TRH
Downregulated by T4, T3
Travels through portal venous system to
cavernous sinus, body.
 Stimulates several processes
 Iodine uptake
 Colloid endocytosis
 Growth of thyroid gland
TSH Response
Iodine states
 Normal Thyroid
 Inactive Thyroid
 Hyperactive Thyroid
Hypothyroid




Symptoms – fatigability, coldness, weight gain,
constipation, low voice
Signs – Cool skin, dry skin, swelling of
face/hands/legs, slow reflexes, myxedema
Newborn – Retardation, short stature, swelling of
face/hands, possible deafness
Types of Hypothyroidism




Primary – Thyroid gland failure
Secondary – Pituitary failure
Tertiary – Hypothalamic failure
Peripheral resistance
Hypothyroid
 Cause is determined by
geography
 Diagnosis
 Low FT4, High TSH
(Primary, check for
antibodies)
 Low FT4, Low TSH
(Secondary or Tertiary,
TRH stimulation test, MRI)
 Treatment
 Levothyroxine (T4) due to longer half life
 Treatment prevents bone loss, cardiomyopathy,
myxedema
Goiter
 Endemic goiter
 Caused by dietary deficiency of Iodide
 Increased TSH stimulates gland growth
 Also results in cretinism
 Goiter in developed countries
 Hashimoto’s thryoiditis
 Subacute thyroiditis
 Other causes
 Excess Iodide (Amiodarone, Kelp, Lithium)
 Adenoma, Malignancy
 Genetic / Familial hormone synthesis defects
Hyperthyroid



Symptoms – Palpitations, nervousness, fatigue,
diarrhea, sweating, heat intolerance
Signs – Thyroid enlargement (?), tremor
Lab workup


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TSH
FT4
RAIU
Other Labs
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Anti-TSH-R Ab, Anti-TPO Ab, Anti-TBG Ab
FT3
FNA
MRI, US
Hyperthyroid
 Common Causes





*Graves
Adenoma
Multinodular Goiter
*Subacute Thyroiditis
*Hashimoto’s Thyroiditis
 Rare Causes
 Thyrotoxicosis factitia, struma ovarii, thyroid
metastasis, TSH-secreting tumor, hamburger
The Endocrine Glands
 Parathyroid Glands
 Secretes parathyroid hormone
 regulates plasma calcium (osteoclast activity)
 regulates phosphate levels
Calcium
Regulation
Parathyroid
Calcium
 Required for muscle contraction, intracellular
messenger systems, cardiac repolarization.
 Exists in free and bound states
 Albumin (40% total calcium)
 Phosphate and Citrate (10% total calcium)
 Concentration of iCa++ mediated by




Parathyroid gland
Parafollicular C cells
Kidney
Bone
Parathyroid Gland
 This gland only
secretes one
hormone:
Parathyroid
Hormone (or
PTH)
 PTH function (we
began learning this
when we studied bone):
 increases blood
calcium (Ca2+)
levels and
decreases blood
phosphate (PO42-
PTH function (continued)
 How does PTH work?
 PTH causes Ca2+ & PO42- to be released from bone
into blood (by increasing osteoclast activity)
 PTH causes the kidneys to remove PO42- ions from
the urine
 PTH increases vitamin D production, so that you
absorb more Ca2+ during digestion
 PTH is regulated by blood calcium levels-- not
by other glands!
Parathyroid Hormone
 Produced by Parathyroid Chief cells
 Secreted in response to low iCa++
 Stimulates renal conversion of 25-(OH)D3 to
1,25-(OH)2D which increases intestinal Ca++
absorption
 Directly stimulates renal Ca++ absorption and
PO43- excretion
 Stimulates osteoclastic resorption of bone
Calcitonin
 Produced by Parafollicular C cells of Thyroid
in response to increased iCa++
 Actions
 Inhibit osteoclastic resorption of bone
 Increase renal Ca++ and PO43- excretion
 Non-essential hormone. Patients with total
thyroidectomy maintain normal Ca++
concentrations
 Useful in monitoring treatment of Medullary
Thyroid cancer
 Used in treatment of Pagets’, Osteoporosis
Vitamin D
 Sources
 Food – Vitamin D2
 UV light mediated cholesterol metabolism – D3
 Metabolism
 D2 and D3 are converted to 25(OH)-D by the liver
 25(OH)-D is converted to 1,25(OH)2-D by the
Kidney
 Function
 Stimulation of Osteoblasts
 Increases GI absorption of dietary Ca++
Hypocalcemia

Decreased PTH




Resistance to PTH



Genetic disorders
Bisphosphonates
Vitamin D abnormalities



Surgery
Hypomagnesemia
Idiopathic
Vitamin D deficiency
Rickets (VDR or Renal hyroxylase abnormalities)
Binding of Calcium


Hyperphosphate states (Crush injury, Tumor lysis, etc.)
Blood Transfusion (Citrate)
Hypercalcemia

Hyperparathyroidism

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Malignancy
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Overproduction of 1,25 (OH)2D
Drug-Induced
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Humoral Hypercalcemia
PTHrP (Lung Cancer)
Osteoclastic activity (Myeloma, Lymphoma)
Granulomatous Diseases


Primary, Secondary, Tertiary
MEN Syndromes
Thiazides
Lithium
Milk-Alkali
Vitamin A, D
Renal failure
Hypercalcemia

Signs & Symptoms

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Medical Treatment

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Bones (Osteitis fibrosa cystica, osteoporosis, rickets)
Stones (Renal stones)
Groans (Constipation, peptic ulcer)
Moans (Lethargy, depression, confusion)
SERM’s (Evista)
Bisphosphonates (Pamidronate)
Calcitonin (for severe cases)
Saline diuresis
Glucocorticoids (for malignant/granulomatous diseases)
Avoid thiazide diuretics
Surgical Treatment


Single vs. Double adenoma – simple excision
Multiple Gland hyperplasia – total parathyroid with autotransplant vs.
3½ gland excision
Primary
Hyperparathyroidism
 Diagnosis
 Signs & Symptoms
 Elevated serum calcium
 Elevated PTH
 Etiology





Solitary Adenoma (80-85%)
Double Adenomas (2-4%)
Muliple Gland Hyperplasia (10-30%)
Parathyroid Carcinoma (0.5%)
MEN syndromes (10% of MGH have MEN 1)
Parathyroidectomy

1990 NIH Guidelines



Serum Ca++ > 12 mg/dl
Hypercalciuria > 400 mg/day
Classic symptoms

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Nephrolithiasis
Osteitis fibrosa cystica
Neuromuscular disease
Cortical bone loss with DEXA Z score < -2
Reduced creatinine clearance
Age < 50
Other considerations



Vertebral osteopenia
Vitamin D deficency
Perimenopause
The Endocrine Glands
 Adrenal Medulla
 Situated directly atop each kidney and
stimulated by the sympathetic nervous
system
 Secretes the catecholamines
 Epinephrine: elicits a fight or flight response
 Increase H.R. and B.P.
 Increase respiration
 Increase metabolic rate
 Increase glycogenolysis
 Vasodilation
The Endocrine Glands
 Adrenal Cortex
 Secretes over 30 different steroid hormones
(corticosteroids)
 Mineralocorticoids
 Aldosterone: maintains electrolyte balance
 Glucocorticoids
 Cortisol:
 Stimulates gluconeogenisis
 Mobilization of free fatty acids
 Glucose sparing
 Anti-inflammatory agent
The Endocrine Glands
 Pancrease:
 Located slightly behind the stomach
 Insulin: reduces blood glucose
 Facilitates glucose transport into the cells
 Promotes glycogenesis
 Inhibits gluconeogensis
 Glucagon: increases blood glucose
The Endocrine Glands
 Gonads
 testes (testosterone) = sex characteristics
 muscle development and maturity
 ovaries (estrogen) = sex characteristics
 maturity and coordination
 Kidneys (erythropoietin)
 regulates red blood cell production
The Endocrine Response to
Exercise
 Table 5.3 Page 172
Regulation of Glucose
Metabolism During Exercise
 Glucagon secretion increases during exercise
to promote liver glycogen breakdown
(glycogenolysis)
 Epinephrine and Norepinephrine further
increase glycogenolysis
 Cortisol levels also increase during exercise for
protein catabolism for later gluconeogenesis.
 Growth Hormone mobilizes free fatty acids
 Thyroxine promotes glucose catabolism
Regulation of Glucose
Metabolism During Exercise
 As intensity of exercise increases, so does
the rate of catecholamine release for
glycogenolysis
 During endurance events the rate of glucose
release very closely matches the muscles
need.
(fig 5.9, pg. 174)
 When glucose levels become depleted,
glucagon and cortisol levels rise significantly
to enhance gluconeogenesis.
Regulation of Glucose
Metabolism During Exercise
 Glucose must not only be delivered to the
cells, it must also be taken up by them.
That job relies on insulin.
 Exercise may enhance insulin’s binding to
receptors on the muscle fiber.
 Up-regulation (receptors) occurs with
insulin after 4 weeks of exercise to increase
its sensitivity (diabetic importance).
Regulation of Fat Metabolism
During Exercise
 When low plasma glucose levels occur, the
catecholamines are released to accelerate
lypolysis.
 Triglycerides are reduced to free fatty acids by
lipase which is activated by: (fig. 5.11, pg.
176)




Cortisol
Epinephrine
Norepinephrine
Growth Hormone
Hormonal Effects on Fluid
and Electrolyte Balance
 Reduced plasma volume leads to release of
aldosterone which increases Na+ and H2O
reabsorption by the kidneys and renal
tubes.
 Antidiuretic Hormone (ADH) is released
from the posterior pituitary when
dehydration is sensed by osmoreceptors,
and water is then reabsorbed by the
kidneys.
Adrenal Glands
An adrenal gland is found on top of each kidney.
Each adrenal gland has two regions that carry out
separate functions!
•The adrenal medulla
•The adrenal cortex
We will cover each of
these two regions
separately in the next few
slides.
The Adrenal Medulla
Acts very much like a part of the sympathetic
nervous system (fight or flight)
Secretes two amines:
 norepinephrine (20%)
 epinephrine (80%)
Stimulated by preganglionic neurons directly, so
controlled by the hypothalamus as if part of the
autonomic nervous system, NOT by tropic
hormones
The Adrenal Cortex
Acts like a regular endocrine organ
Secretes many hormones, but most importantly
secretes the following steroids:
 aldosterone
 cortisol
 sex hormones
Aldosterone and cortisol require further
explanation (while sex hormone production will be
covered later this semester)
More about Adrenal Cortex
Hormones
Aldosterone:
Cortisol:
Considered a
mineralocorticoid
Regulates “mineral electrolyte”
levels in the blood (for example:
Na+ and K+ ions)
How is aldosterone controlled?
 blood plasma ion
concentrations affect its
secretion directly (but not
always strongly)
 kidney secretes renin in
response to altered electrolyte
levels, which triggers
angiotensin activation in the
blood, which leads to
aldosterone secretion
Considered a glucocorticoid
Overall effect of cortisol:
 Helps to keep blood glucose
concentration within a normal
range between meals
Specific actions of cortisol:
 increases amino acid
concentration in the blood (by
inhibiting protein synthesis in
select tissues)
 promotes use of fat for energy
production in our bodies (rather
than glucose)
 stimulates the liver to synthesize
glucose (not from carbohydrates,
but from amino acids and
The Pancreas
 This gland has both endocrine and exocrine
functions… we’ll only cover the endocrine portion
now (exocrine is for digestion)
 The endocrine portion of the gland contains three
types of cells, each making a different hormone,
arranged into groups called Islets of Langerhans
 alpha cells: secrete glucagon
 beta cells: secrete insulin
 delta cells: secrete SS (somatostatin)
 Note that these pancreatic hormones are involved
in blood glucose regulation, and problems with
them can lead to diabetes.
Blood Glucose Regulation by
the
Pancreas
Glucagon:
Insulin:
It works on the liver to
cause the production of
glucose via:
 glycogenolysis
 gluconeogenesis
It is regulated by blood
glucose levels directly:
It works on the liver to
remove glucose from
the blood via:
 making glycogen
 preventing
gluconeogenesis
 increasing glucose
transport into cells
 secreted when blood
glucose drops (before next It is also regulated by
blood glucose levels
meal)
directly
Note: glucagon and insulinPrevents
work in hyperglycemia
opposition, and
Prevents hypoglycemia
their combined effects control blood glucose
Pineal Gland
Secretes only one hormone: melatonin
Involved in your circadian rhythm (your
recognition of day and night times):
 melatonin secretion decreases in the day
 melatonin secretion increases at night
Melatonin is also involved in longer rhythms,
like monthly and seasonal… and is
thought to be involved in the female
menstrual cycle and maybe in the onset of
puberty
Other Endocrine Glands
 Thymus Gland: secretes thymosins
which are involved in white blood cell
production
 Reproductive glands (the gonads): the
ovaries and the testes produce sex
hormones
 Others: too specific for now, we’ll get to
them as we continue this semester.