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Transcript
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