Download Function Nervous System Endocrine System

Endocrine System
Carl B. Goodman, Ph.D.
College of Pharmacy & Pharmaceutical Sciences
Florida A&M University
308E FSH-SRC
599-3128
[email protected]
Endocrine System: Homeostasis

Hormone
- Regulatory molecules
secreted into blood stream

Endocrine Gland
- Ductless glands contains
secretory cells
- Synthesis or produce
hormones

Effector
- Target cells or tissues
- Contains receptors to
produce some physiological
response
Endocrine System vs Nervous System
Function
Secretory Cells
Nervous System
Neuron
Endocrine System
Glandular Epithelial Cells &
Neurosecretory Cells
Distance
Short (Synapse)
Long (Blood)
Location of Receptors
In Effector Cells
Plasma Membrane Plasma Membrane
& Within the Cell
Characteristics of
Regulatory Effects
Appears Rapid,
Short Lived
Slow, Long Lasting
Diagram
Pre & Post
Neurons
Synaptic Target Cells
Endocrine System vs Nervous System
Function
Overall Function
Nervous System
Regulate Effectors
*HOMEOSTASIS
Endocrine System
Regulate Effectors
*HOMEOSTASIS
Control Feedback Loop
Yes (Nervous Reflex)
Yes (Endocrine Reflex)
Chemical Messenger
Neurotransmitter
Hormone
(Proteins or Steroids)
Effector Tissues
Muscle & Glandular
Tissues
All Cell Types
*Muscles, Bones, Glandular
Effector Cells
Post Synaptic Neurons Target Cells
Endocrine Action
Endocrine System
Endocrine Glands
CNS: Pituitary Gland
Periphery: Pancreas, Thyroid,
Parathyroid, Adrenal, Testes
and Ovaries
Organs with Partial Endocrine
Functions
Hypothalamus,
Pineal
Gland, Stomach, Duodenum,
Liver, Thymus, Heart, Skin,
Kidney, Lung and Placenta
Types of Hormones: Lipid Soluble

Steroids
- Cortisol
- Aldosterone
- Androgens
- Estrogen/Progesterone
- Testosterone
- Calcitrol (Kidney)

Gas
- Nitric Oxide (NO)

Thyroids
- Triiodothyronine (T3)
- Thyroxine (T4)
Types of Hormones: Water Soluble

Glycoproteins
- Follicle Stimulating Hormone (FSH)
- Luteinizing Hormone (LH)
- Thyroid Stimulating Hormone (TSH)

Peptides
- Anti-diuretic Hormone (ADH) (8 AA)
- Oxytocin (8 AA)
- Melanocyte Stimulating Hormone (MSH)
- Thyroid Releasing Hormone (TRH)

Proteins
- Growth Hormone (191), Calcitonin (32 AA),
Prolactin, Insulin (21 & 30 AA), ACTH (39
AA), Parathyroid Hormone (84 AA)

Fatty Acids (Arachidonic acid)
- Leukotrienes
- Prostaglandins
- Thromboxanes
- Prostacyclins
Types of Hormones: Amino Acids

Amines (Water Soluble)
- Norepinephrine (Tyrosine)
- Epinephrine (Tyrosine)
- Melatonin (Tryptophan)
- Serotonin (Tryptophan)
- Histamine (Histadine)

Iodinated Amino Acid
- Thyroxine (T4)
- Triiodothyronine (T3)
Hormone Circulation

Endocrine Action:
hormone is distributed in
blood and binds to distant
target cell

Paracrine Action:
hormone acts locally by
diffusing from its source to
target
cells
in
the
neighborhood

Autocrine Action:
hormone acts on the same
cell that produced it
Hormone Transport in Blood

Protein hormones circulate in free form in blood

Steroid (lipid) & thyroid hormones must attach to
transport proteins (Carrier Molecules) synthesized by liver
– improve transport by making them water-soluble
– slow loss of hormone by filtration within kidney
– create reserve of hormone
• only .1 to 10% of hormone is not bound to transport
protein = free fraction

Synthesis and Metabolism
General Mechanisms of Hormone Action

Hormone binds to cell surface or receptor inside target cell

Cell may then:
– synthesize new molecules (Protein Synthesis)
– change permeability of membrane (Ion channels)
– alter rates of reactions (Enzymes)

Each target cell responds to hormone differently
– Liver cells: insulin stimulates glycogen synthesis
– Adipose: insulin stimulates triglyceride synthesis

Circadian Rhythm for all Hormones (Basal Level)
- Ex. Cortisol: increased daytime and decreased at night
Hormone Interaction

Synergistic

Permissive- a second hormone, strengthens the effects of the first
Ex. thyroid strengthens epinephrine’s effect upon lipolysis or Estrogen
and Progesterone are need for maturation of follicle

Antagonistic
ex. Insulin and Glucagon

Prehormone
ex. T4 converted to T3
ex. Vitamin D3 converted to 1,25 dihydroxyvitamin D3
Role of Hormone Receptors

Constantly being synthesized & broken down

A range of 2,000-100,000 receptors / target cell

Down-regulation (Hypersecretion of Hormone)
– excess hormone, produces a decrease in number of
receptors
• receptors undergo Endocytosis and are degraded
– decreases sensitivity of target cell to hormone

Up-regulation (Hyposecretion of Hormone)
– deficiency of hormone, produces an increase in the number
of receptors
– target tissue more sensitive to the hormone

H + R = HR Complex
Intracellular Chemical Signal

Autocrine: secreted in a local area ex. Prostaglandins

Paracrine: neighboring cell ex. Histamine, Prostaglandins

Hormone: secreted in blood… ex. Insulin, T4, and T3

Neurohormone: produced by neurons ex. Oxytocin, ADH

Neurotransmitter or Neurohumor:

Pheromone:
produced by neurons and secreted
into synapse ex. Acetylcholine and Epinephrine
pheromones
secreted in environment, modifies behavior ex. Sex
Hormone Signal Transduction Pathway
Steroids Hormone
Protein Hormone
Second Messengers




cAMP
cGMP
Phospholipase C
Ca++
Opposing 2nd Messenger System with Same Hormone
 Beta Adrenergic Receptors
- Relaxation/Dilation = cAMP

Alpha Adrenergic Receptors
- Constriction = Phospholipase C
Feedback Control System
Negative Feedback
Positive Feedback
Hypothalamic-Pituitary System
Neurohypophysis
Adenohypophysis
Pituitary Gland = Hypophysis
Hypothalamic-Pituitary System
Pars Tuberalis
Pars Nervosa
Pars Distalis
Pars Intermedia
Posterior Pituitary Gland: Neurohormones
Anti-diuretic Hormone
(ADH) or Vasopressin

Osmoreceptors near Supraoptic
Nucleus (Dehydration) (Alcohol)

H2O is reabsorbed from the
tubules of the kidney and
returned to the blood instead of
the urine (H20 is conserved)

Decrease in rate of perspiration
during dehydration

Raises Blood Pressure by
constricting Arterioles
Oxytocin

Stimulate contraction of
uterine muscle (smooth
muscle)

Initiate milk ejection from
the Alveolar Cells into the
ducts of the breast in
lactating women
Melanocyte-Stimulating Hormone (MSH)

Pars Intermedia (Corticotroph cells)

Melanocytes - Melanin (Darkening of Skin)

Pre-proopiomelanocortin

2o Addision’s Disease (skin darkening)

Estrogen/Progesterone (skin darkening)
Anterior Pituitary Gland

Growth Hormone (Somatotrophin)
 Prolactin
Tropic Hormones
 Adenocorticotrophic Hormone (ACTH)
 Thyroid Stimulating Hormone (TSH)
 Luteinizing Hormone (LH)
 Follicle Stimulating Hormone (FSH)
Growth Hormone

Produced by somatotrophs (191AA)

Within target cells increases synthesis of Somatomedins and
Insulin-like Growth Factors that act locally or enter bloodstream
– common target cells are liver, skeletal muscle, cartilage and
bone
– increases cell growth & cell division by increasing their
uptake of amino acids & synthesis of proteins
– stimulate lipolysis in adipose so fatty acids used for ATP
– retard use of glucose for ATP production so blood glucose
levels remain high enough to supply brain
Abnormal Levels of Growth Hormone
Hypersecretion of GH
Hyposecretion of GH

During the growth years before
ossification of Epiphyseal
plates, causes increase in rate
of skeletal growth = Gigantism


After the growth years =
Acromegaly
-Excess cartilage growth
forming new bones.
-Enlarged hands, feet, jaws,
separation of teeth,
-*Soft Tissue (forehead and
nose)
During the growth years, results
in stunted body growth =
Pituitary Dwarfism
Prolactin

Hypothalamus regulates lactotroph cells

Primary function is to generate/initiate milk secretion
(Lactation)
1.
During Pregnancy, high prolactin promote development of
breast for milk secretion
2.
At Birth of an Infant, suckling reduces levels of hypothalamic
inhibition and prolactin levels rise along with milk production

Mammary glands are primed with E/P, Cortisol, GH, T4 and
Insulin
Nursing ceases & milk production slows

Abnormal Levels of Prolactin
Hypersecretion of Prolactin
Hyposecretion of Prolactin

Causes lactation in non-nursing
women


Disruption of the menstrual
cycle

(Men) can cause impotence
Insignificant except in women,
who want to nurse feed their
babies
ACTH



Hypothalamus releasing
hormones stimulate
corticotrophs
Corticotrophs secrete ACTH
& MSH
ACTH stimulates cells of the
adrenal cortex that produce
glucocorticoids
&




TSH
Hypothalamus regulates
thyrotroph cells
Thyrotroph cells produce
TSH
TSH stimulates the synthesis
& secretion of T3 and T4
Metabolic rate stimulated
Gonadotrophins
Luteinizing Hormone
 Releasing hormones from
hypothalamus stimulate
gonadotrophs
 Gonadotrophs produce LH
 In females, LH stimulates
– secretion of estrogen
– ovulation of 2nd oocyte from
ovary
– formation of corpus luteum
– secretion of progesterone
 In males, stimulates interstitial
cells to secrete testosterone
Follicle Stimulating Hormone
 Releasing hormone from
hypothalamus controls
gonadotrophs
 Gonadotrophs release
follicle stimulating hormone
 FSH functions
– initiates the formation of
follicles within the ovary
– stimulates follicle cells to
secrete estrogen
– stimulates sperm production
in testes
Pathophysiology of HP Axis
Hypothalamus
Pituitary Gland
1. Tumors
- increase release of
hormones
- destruction of
hypothalamus
2. Drugs - increase or decrease
hormones release
3. Heavy blow to the head
4. Infarction of the Primary
plexus of the hypophyseal
portal system
1. Tumors
- increase release of
hormones
- destruction of pituitary
gland
2. Drugs - increase or decrease
hormones release
3. Infarction of the Secondary
plexus of the hypophyseal
portal system
Target Cell Failure

Receptor-associated disorders
– Decrease in number of receptors
– Impaired receptor function
– Presence of antibodies against specific
receptors
– Antibodies that mimic hormone action
– Unusual expression of receptor function
Disease of the Posterior Pituitary

Syndrome of inappropriate antidiuretic
hormone secretion (SIADH)
– Hypersecretion of ADH
– For diagnosis, normal adrenal and thyroid
function must exist
– Clinical manifestations are related to
enhanced renal water retention,
hyponatremia, and hypoosmolarity
Disease of the Posterior Pituitary

Diabetes Insipidus
– Insufficiency of ADH
– Polyuria and polydipsia
– Partial or total inability to concentrate the
urine
– Neurogenic
• Insufficient amounts of ADH
– Nephrogenic
• Inadequate response to ADH
Disease of the Anterior Pituitary

Hypopituitarism
– Pituitary infarction
• Sheehan syndrome
• Hemorrhage
• Shock
– Others: head trauma, infections, and
tumors
Disease of the Anterior Pituitary

Hypopituitarism
– Panhypopituitarism
•
•
•
•
ACTH deficiency
TSH deficiency
FSH and LH deficiency
GH deficiency
Disease of the Anterior Pituitary

Hyperpituitarism
– Commonly due to a benign, slow-growing
pituitary adenoma
– Manifestations
• Headache and fatigue
• Visual changes
• Hyposecretion of neighboring anterior pituitary
hormones
Adrenal Gland



Small bilateral structures located superior or at the
apex of each kidney
Weigh about 5 grams each
2 Major regions: Cortex and Medulla
Cross Section & Histology
Minerocorticoids
Aldosterone
 95% of hormonal activity due to
aldosterone
 Functions
– increase reabsorption of Na+ with Cl- ,
bicarbonate and water following it
– promotes excretion of K+ and H+
Regulation of Aldosterone
Glucocorticoids

95% of hormonal activity is due to cortisol
 Functions = help regulate metabolism
–
–
–
–
increase rate of protein catabolism & lipolysis
conversion of amino acids to glucose
stimulate lipolysis
provide resistance to stress by making nutrients
available for ATP production
– raise BP by vasoconstriction
– anti-inflammatory effects reduced (skin cream)
• reduce release of histamine from mast cells
• decrease capillary permeability
• depress phagocytosis
Pathophysiology of Adrenal Gland
Hypersecretion of Cortisol
Cushing’s Disease/Syndrome
 Central Obesity
 Moon Face & Buffalo Hump
 Hypertension & Hypokalemia
 Hyperglycemia
MCC: Lung Cancer secreting
ACTH
Pathophysiology of Adrenal Gland
Hyposecretion Glucocorticoids
& Minerocorticoids
Addison’s Disease
 Hypotension
 Skin Pigmentation
 Loss of NaCl
 Muscle Weakness
 Unable to resist stress

MCC: Autoimmune Disease
Pathophysiology of Adrenal Gland
Hypersecretion of Aldosterone
Hypersecretion of Androgens
Conn’s Syndrome
 Hypertension
 Hypokalemia
 Metabolic Alkalosis
Congential Adrenal Hyperplasia
 Hirsuitism
• Primary
hyperaldosteronism
(Conn disease)
• Secondary
hyperaldosteronism

MCC: Tumor

MCC: Congential Defect
Androgens

Small amount of male hormone
produced
– insignificant in males
– may contribute to sex drive in females
– is converted to estrogen in
postmenopausal females
Adrenal Medulla





Chromaffin cells receive direct innervation from sympathetic
nervous system
– develop from same tissue as postganglionic neurons
Produce Epinephrine (80%) & Norepinephrine (20%)
Hormones are sympathomimetic
– effects mimic those of sympathetic NS
– Ex. Increase if rate/force of contraction, constricts blood
vessels, dilation of bronchioles, increase metabolic rate
– cause fight-flight behavior (Stress)
Short Term (Epi/NE)
Long Term (Glucocorticoids)
Acetylcholine increase hormone secretion by adrenal medulla
Stimuli: Exercise, Emotional stress, Hypoglycemia
Pathophysiology of Adrenal Medulla
Hypersecretion of Adrenal Medulla Hormones
Episodic Hypertension
 Tumor: Pheochromocytoma
 Epi/NE from adrenal medulla are hormones and their
actions are longer lasting than Epi/NE from the SNS
Hyposecretion of Adrenal Medulla Hormones
 Rare
Thyroid Gland
Thyroid Hormones & Their Effects


T4 (Thyroxine) (Tetra-iodothyronine) 4-Iodine molecules
T3 Triiodothyronine 3-Iodine molecules

Regulates Body’s Metabolic Rate (Calorigenic Effect)
- Increase Oxygen consumption
- Increase Heat production (Heart, Muscle, Visceral Tissues)

Promote Body Growth/Development
- Increase protein synthesis, particularly in muscles and bones
- Initiates cell differentiation

Cardiovascular Effects
- Increase heart rate and contractility
- Increase vascular responsiveness to Epi/NE; Increase BP
Thyroid Hormones & Their Effects

Calcitonin

Produced by the Parafollicular cells (C cells) of the thyroid gland
Inhibits Osteoclast cells
Decrease Ca++ plasma levels
Promote bone deposition
Increase rate of Ca++ and Phosphorus by kidney




Thyroid Hormone Synthesis







Iodide trapping by follicular cells
Synthesis of thyroglobulin (TGB)
Release of TGB into colloid
Iodination of tyrosine in colloid
Formation of T3 & T4 by combining T1
and T2 together
Uptake & digestion of TGB by follicle
cells
Secretion of T3 & T4 into blood
Pathophysiology of Thyroid Gland
Hypersecretion of Thyroid Hormones
Hyposecretion of Thyroid Hormones
Graves’ Disease
 Increase metabolism
 Goiters
 Exophthalamos
Cretinism (Children)
 Mentally retarded
 Stunted growth, dwarfism
 Enlarged tongue and abdomen
MCC: Congential
MCC: Autoimmune
Myxedema (Adults)
 Thick dry skin
 Weakness, fatigue
 Delayed tendon reflex
 Slowed mentation
MCC: Hyperthyroid Trxt
Parathyroid Gland


Regulated by Ca++ Levels (low levels)
Stimulate release of Ca++ from bones
Pathophysiology
 Hypersecretion (Hypercalcemia)
- Factures & cysts of bones
- Calcium deposits in tissues
MMC: Lung Cancer

Hyposecretion (Hypocalcemia)
– Tetany: Flexion of wrist and joints (Carpopedal spasm)
MMC: Removal of thyroid gland
Pancreas
Pancreatic Cell Types

Alpha cells (20%) - Glucagon

Beta cells (70%) - Insulin

Delta cells (5%) -Somatostatin
- Identical to GHIH
- Inhibits both insulin and glucagon
release (Paracrine action)
- Slow absorption of nutrients from GI
tract
 F cells - Pancreatic polypeptide
- Inhibits somatostatin secretion, gall
bladder contraction and secretion of
digestive enzymes by pancreas
THE EFFECTS OF INSULIN ON PLASMA GLUCOSE
Increase in Plasma
Glucose
Pancreas
Beta Cells-Insulin
Adipose Tissue
Skeletal Muscle
Fat
Energy
Liver
Glycogen
Plasma Glucose Levels

All people with diabetes have one thing in common: they have too
much sugar, or glucose, in their blood. A normal blood sugar level for a
person without diabetes is usually about 60-110 milligrams per deciliter
(mg/dL). This is the proper level needed for normal body function.
When the blood sugar level drops too low (hypoglycemia), a person's
ability to reason is impaired; in extreme cases, coma may result. When
the blood sugar is consistently too high (hyperglycemia), a diagnosis
of diabetes is possible.
Diabetes Mellitus

Diabetes mellitus are metabolic diseases
characterized by hyperglycemia resulting
from defects in insulin secretion, insulin
action, or both. Type 2 diabetes, the most
prevalent form of the disease, is often
asymptomatic in its early stages and can
remain undiagnosed for many years.
Approximately 5.4 million adults in the U.S.
have undiagnosed type 2 diabetes.
Diabetes Mellitus
Type I
•
Type 2
Results from an autoimmune
destruction of pancreatic Beta
cells
• Insulin is secreted, but it is
ineffective
in
normalizing
plasma glucose
• Occurs usually at less than 20-30
years of age (Juvenile Onset)
• Cardinal finding-increments in
plasma insulin do not lead to the
expected increases in glucose
disposal. This is referred to as
“Insulin Resistance”
• Cardinal finding-inability to secrete
even the modest amount of
insulin to suppress ketone
formation
• People with type 1 diabetes must
take daily insulin injections to stay
alive. Type 1 diabetes accounts
for 5-10 percent of diabetes.
• Type 2 diabetes accounts for 9095 percent of diabetes. It is
nearing epidemic proportions,
due to an increased number of
older Americans.
Symptoms of DM I & II
Type 1 Diabetes:
· Frequent urination
· Unusual thirst
· Extreme hunger
· Unusual weight loss
· Extreme fatigue
· Irritability
Type 2 Diabetes:
· Any of the type 1 symptoms
· Frequent infections
· Blurred vision
· Cuts/bruises that are slow to heal
· Tingling/numbness in the hands or
feet
· Recurring skin, gum or bladder
infections
* Often people with Type 2 diabetes have no symptoms.
COMPLICATION CAUSED BY
TYPE 2 DIABETES
Unchecked diabetes can lead to serious conditions. These include:

Heart disease, stroke, and blood-vessel (cardiovascular) diseases. Cardiovascular
disease is by far the leading cause of death in the United States, but people with diabetes
are at much higher risk.

Kidney disease. Also called nephropathy, this complication happens when the kidney's
"filter mechanism" is damaged and protein leaks into urine in excessive amounts and
eventually the kidney fails.

Eye diseases. Diabetes is a leading cause of damage to the retina at the back of the eye
and also increases risk of cataracts and glaucoma.

Nervous-system problems. Nerve damage, especially in the legs and feet, may interfere
with the ability to sense pain and contributes to serious infections.
Pathogenesis of Type 2 DIABETES
Progressive metabolic defect whereby a disruption in the
delicate balance by which insulin target tissues communicate
with the pancreatic beta-cells and vice versa to maintain normal
glucose homeostasis

Impaired insulin secretion
 Insulin resistance
 Increased rate of endogenous hepatic glucose production (HGP)
 Progression of insulin resistance leads to a compensatory
hyperinsulinemia
DECREASE INSULIN LEVELS
PRODUCES THREE MAJOR EFFECTS IN DIABETICS
1) Decreased utilization of glucose by the body's cells,
resulting in elevated blood glucose concentrations;
2) Increased mobilization of fats from storage sites,
resulting in abnormal fat metabolism and lipid
deposition in the vascular walls, leading to
atherosclerosis; and
3) Depletion of proteins in body tissues.
HOW DO WE IDENTIFY THOSE
PATIENTS WITH HYPERGLYCEMIA?
“Blood Glucose Tests”
1) Screening Test
2) Diagnostic Test
SCREENING TESTS
It is estimated that about 2.5% of the US population may have diabetes
that will go undetected unless screening tests are performed.
WHO SHOULD BE SCREENED:
 Persons with a strong family history of diabetes mellitus
 Persons who are markedly obese
 Women with an obstetrical history resulting in morbidity or a history of babies of
over 9 pounds at birth
 All women between 24 and 28 weeks of pregnancy
 Anyone with recurrent skin, genital, or urinary tract infections
 Persons older than 65 years of age
 Certain races (American Indian, Hispanic, and African American)
 Persons who have had previous impaired glucose tolerance
 Persons who are hypertensive (blood pressure at or above 140/90)
 Persons who have an HDL cholesterol level (the "good" cholesterol) of 35 mg/dL
or lower and/or a triglyceride level of 250 mg/dL or higher
The American Diabetes Association
Diabetes Risk Test
HEMOGLOBIN A1c (HbA1c)
BLOOD TEST

Measures glycosylated hemoglobin, a molecule that gauges
how well diabetics controlled their blood glucose during the
previous months.

Glycosylated hemoglobin forms when hemoglobin molecules,
which are found in red blood cells, link up with glucose
molecules. The more glucose in the blood, the more hemoglobin
becomes glycosylated. Once glycosylated, hemoglobin stays
that way until the red blood cell dies -- about 120 days.

The result is given as a percentage. People who don't have
diabetes typically have HbA1c readings of about 4% to 5.5%.
Fasting Plasma Glucose Test

The fasting plasma glucose test is the preferred way
to diagnose diabetes. It is easy to perform and
convenient. After you have fasted overnight (at least
8 hours), a single sample of your blood is drawn at
the doctor’s office and sent to the laboratory for
analysis.

Normal fasting plasma glucose levels are less than
110 milligrams per deciliter (mg/dL). Fasting plasma
glucose levels of more than 126 mg/dL on two or
more tests on different days indicate diabetes.
INSULIN PREPARATIONS
Reaches Blood
Peak
Duration of Action
Rapid-acting
(Lispro)
15 minutes
30-90 minutes
5 hours
Short-acting
(Regular)
30 minutes
2-4 hours
4-8 hours
Intermediate-acting
(NPH and Lente)
2-6 hours
4-14 hours
14-20 hours
Long-acting
(Ultralente)
6-14 hours
No peak or a small
peak 10-16 hours
20-24 hours
INSULIN
Pineal Gland

Located dorsal of the diencephalon region near the
3rd ventricle

Comprises 2 systems:
1) NS, receiving visual nerve input
-Helps determine: day length- daily and seasonal cycles (time
length); lunar cycle-menstrual cycle
2) ES, secretes Melatonin (Induces Sleep)
-Support the Biological Clock
-Regulates our eating, sleeping, female reproductive cycle and
behavior
Thymus Gland
• Important role in maturation of T cells
• Hormones produced by gland promote the
proliferation & maturation of T cells
– thymosin
– thymic humoral factor
– thymic factor
– thymopoietin