Download (12) Endocrine System

Endocrine System
Dr. Carmen Rexach
Physiology
Mt San Antonio College
Relationship between endocrine and
neural physiology
• Both neurons and endocrine cells can secrete into the
blood stream
• Endocrine cells and neurons generate electrical
potentials when depolarized
• Peptides produced by endocrine cells have
neurotransmitter function & can act as hormones
• A single cell can produce biogenic amine
neurotransmitters and peptide hormone molecules
• A single gene can be transcribed/translated to produce
either peptide neurotransmitter or hormone
Structural classification of
hormones
• Amino Acid derivatives
• Peptide hormones
• Lipid derivatives
Amino Acid Derivatives
• Derivatives of Tyrosine
– Catecholamines
• epinephrine and norepinephrine
(adrenal medulla)
• dopamine (hypothalamus)
– Thyroid hormones
• T3, T4
• Derivatives of Tryptophan
– Melatonin (pineal gland)
Peptide Hormones
• Short polypeptides (<200 amino acids)
– ADH, ACTH, insulin, PTH, Calcitonin,
ANF, GI tract hormones and others
• Proteins
– TSH,LH, FSH, erythropoietin, renin,
inhibin
Lipid derivatives
• Steroid hormones
– cholesterol derivatives
– androgens, estrogens, progestins, hormones of adrenal
cortex, and others
• Eicosanoids
– arachadonic acid derivatives
– prostaglandins, leukotrienes, thromboxanes,
prostacyclins, etc.
Lipid derivatives
Prohormones and prehormones
• Prohormones
– long chained precursor
– cut and spliced to produce endproduct(s)
• Prehormones
– produced in inactive form
– require modification to become active
– examples
• T4
T3 at target cell
• testosterone
• Vitamin D3
Response at the target cell
• Hormone must be recognized by specific
cell receptor
• Hormone/receptor complex must be
coupled to signal-transduction
mechanism
• The generated signal must cause a
change in intracellular processes by
changing the activity or concentration
of enzymes, carrier proteins, etc.
Hormone interactions
• Synergistic and permissive effects
– synergistic: working together
• additive (epinephrine, norepinephrine on heart)
• complementary (FSH/LH on spermatogenesis)
– permissive: potentiation
• increased response of target cell to a 2nd
hormone
• increased activity of second hormone
• Antagonistic effects: opposition
– insulin/glucagon
Hormone concentration
• Half-life of hormone
– Time required for the blood [hormone] to be
reduced to ½ reference level
• Minutes to days
• Concentration
– physiological level
• amount necessary for normal function
– pharmacological level
• too much
– incidental binding to protein receptors with
similar structure but less affinity
– secondary conversion into other products
– Results: varying effects in body
Upregulation and downregulation
• Upregulation (Priming effect)
– chronically low levels of hormone in ECF
leads to increase of number and sensitivity
of protein receptors for that hormone
• Downregulation (Desensitization)
– chronically high levels of hormone in the ECF
leads to decrease in the number and
sensitivity of protein receptors for that
hormone
– Prevented by pulsatile secretions
Relationship to NIDDM
• Non-insulin dependent diabetes
mellitus
– obesity
– increased sugar consumption leads to increase
in circulating insulin
– chronic increase in insulin levels leads to
downregulation of insulin receptors on cell
surfaces
– cells become refractory to insulin
– can result in atrophy of the β cells and insulin
dependence
Mechanisms of hormone
action
• Same category = similar mechanism
• Determined by:
– location of receptor
– cellular response to receptor activation
• Location of Receptor
– Nonpolar hormones
• in nucleus of target cell
• in cytoplasm of target cell
– Polar hormones
• on outer surface of plasma membrane
Steroid and thyroid
hormones
• Nonpolar
– into plasma attached to carrier proteins
– dissociate in blood near target
– hormone into target
• moves into cell and binds to intracellular
receptor
• alterations allow for direct binding to DNA
• Result: genetic transcription (mRNA
synthesis)
Steroid hormones
Result: turn a key
metabolic pathway
on or off
Steroid Hormones:
In nucleus
• DNA-binding domain
of receptor binds to
specific HRE of the
DNA.
• Dimerization occurs.
– Process of 2 receptor
units coming together
at the 2 half-sites.
• Stimulates
transcription of
particular genes.
Thyroid
hormones
T4
T3
Result: turn
key enzymes
in a metabolic
pathway on or
off
Mechanism of Thyroid
Hormone Action
• T4 passes into cytoplasm
and is converted to T3.
• Receptor proteins located
in nucleus.
– T3 binds to ligand-binding
domain.
– Other half-site is vitamin
A derivative (9-cisretinoic) acid.
• DNA-binding domain can
then bind to the half-site
of the HRE.
– Two partners can bind to
the DNA to activate HRE.
• Stimulate transcription
of genes.
Peptide hormones
• Polar = restricted to cell surface
• Utilize second messenger system
Second messenger = cAMP
α
G-protein
Protein kinase
Adenylate cyclase
ATP
PO43-
cAMP +Pi
Result: Turn key enzyme in a metabolic
pathway on or off
Second messenger = Ca++
epi
α adrenergic receptor
PLC
Ca++
DAG
PIP2
IP3
Ca++
Protein kinase
calmodulin
Epi Can Act Through Two
2nd Messenger Systems
Remember
• Different hormones have different
effects on same target cell
• Response of target cell to same
second messenger can differ in
different cells
Endocrine glands and
their products
Pituitary gland
structure
Anterior pituitary
• Trophic effects:
– High blood
[hormone] causes
target organ to
hypertrophy.
– Low blood
[hormone] causes
target organ to
atrophy.
Hormones of anterior pituitary
• GH = somatotropin
– Generalized growth promoting effects
• TSH = thyrotropin
– Regulates activity of thyroid gland
• ACTH = corticotropin
– Regulates activity of adrenal cortex
• PRL = prolactin
– Mammary growth, development, lactogenesis
• Gonadotropins
– FSH = folliculotropin
– LH = leutotropin
Pituitary hormones: pars
intermedia & posterior
• Pars intermedia
– MSH
– Beta (β)-endorphins
• Posterior pituitary
– ADH
– oxytocin
Hypothalamic Control of
Posterior Pituitary
• Hypothalamus
neuron cell bodies
produce:
– ADH: supraoptic
nuclei.
– Oxytocin:
paraventricular
nuclei.
• Transported along
the hypothalamohypophyseal tract.
• Stored in posterior
pituitary.
• Release controlled
by neuroendocrine
reflexes.
Hypothalamic control of
anterior pituitary
• Hypothalamopituitary portal vessel
• releasing hormones: polypeptides released by
the hypothalamus
– TRH
TSH
– CRH
ACTH
– GnRH
FSH/LH
– GHRH
GH
• inhibiting hormones
– PIH
PRL
– Somatostatin
GH
Negative feedback loops
Hypothalamus
Increased secretion hormone #1
stimulus
-
-
-
Increased plasma hormone #1
Anterior pituitary
Increased secretion hormone #2
Increased plasma hormone #2
3rd Endocrine gland
Increased secretion hormone #3
Increased plasma hormone #3
Target cells of hormone #3
Respond to hormone #3
Positive feedback effect
• Amplifies initial biological effect of
hormone
estradiol
LH
Pituitary gland disorders
Identical twins
Acromegaly
Acromegaly vs. Gigantism
Influence of higher brain
functions
• Emotions
• Stress
• Circadian rhythms
– somatotropin released in greatest
quantities during first 90 minutes of
sleep
– estradiol on GnRH response
Adrenal gland
Functions of the adrenal cortex
• Mineralocorticoids
– zona glomerulosa
– aldosterone = Na+/K+ regulation
• Glucocorticoids
– zona fasciculata
– cortisol and corticosterone
– protein and carbohydrate
metabolism
• Sex steroids
– zona reticularis
– androgens and estrogens =
maintenance of secondary sex
characteristics
Adrenal Cortex
Stress and the adrenal gland
• Stimulate pituitary-adrenal axis
due to chronic controlled stress
– increased secretions of ACTH
– increased secretions of glucocorticoids
• Sympathetic response
– stimulation of adrenal medulla
– response to physical challenge or
physically challenging stressors
Stress and the Adrenal Gland
• Three phase
response
– 1) Alarm phase
• Adrenal glands
activated.
– 2) Stage of
resistance
• Stage of
readjustment.
– 3) Stage of
exhaustion
• Sickness and/or
death if
readjustment is not
complete.
Adrenal gland disorders:
Cushing’s syndrome
Caused by excess production of ACTH
Classic symptoms seen in this 23 y.o. female
hirsutism (face)
central obesity
hyperpigmentation & striae
Cushing’s syndrome
Thyroid gland
Thyroid Hormones
• located just below
the larynx
• largest of the pure
endocrine glands
• Follicular cells
secrete thyroxin
• Parafollicular cells
secrete calcitonin
Production of thyroid
hormones
• 2I- + H2O2
I2
– iodide enters cell by secondary cotransport with Na+
• I2 + HO
Tyrosine
• DIT + DIT
• MIT + DIT
MIT
CH2CHCOOH
DIT
NH2
Tetraiodothyronine
T4 (thyroxine)
T3
triiodothyronine
Production and release
• T3 and T4 produced.
• TSH stimulates pinocytosis into the
follicular cell.
– Enzymes hydrolyze T3 and T4 from
thyroglobulin.
• Attached to TBG and released into
blood.
Secretion of T3/T4
• T4 circulates bound to protein
• Protein allows for transport in the
plasma and through the cytosol in the
cell for access to nuclear receptors
Binding proteins
• three major binding proteins
produced in the liver
– thyroxine-binding pre-albumin (TBPA)
• binds 70-75% of T4
– thyroxine-binding globulin (TBG)
• binds 15-20% of T4
– albumin
• 5-10% of T4
T3 vs T4
• Both of these are water insoluble, but
certain binding proteins have greater
affinity for T4
• T4 concentrations in humans 50x’s greater
than T3
• Functions
– T3 physiologically relevant hormone
– T4 involved in negative feedback loop on pituitary
production of TSH & production of TRH by the
hypothalamus
Effects
• Protein synthesis
• maturation of nervous system
• increased BMR
– during prolonged fasting plasma T3 levels
decrease (ever wonder why it is harder to loose
weight when you start dieting?? Your body is
prolonging your survival by minimizing its
energy usage!)
• Thyroid diseases
– Goiter
– Graves disease
– Cretanism/myxedema
Diseases of the Thyroid
• 1) Iodine-deficiency
(endemic) goiter
• 2) Abnormal growth of the
thyroid gland.
• 3) In the absence of
sufficient iodine, cannot
produce adequate amounts
of T4 and T3.
• 4) Lack of negative
feedback inhibition.
• 5) Stimulates TSH, which
causes abnormal growth.
Goiter
Graves disease: hyperthyroidism
exopthalmos
Digital clubbing
Myxedematous cretinism
20-year-old African
male with three cretin
women of the same age
Characteristics:
Mental retardation
Severe growth retardation
Delayed sexual maturation
Incomplete maturation of
features
Puffy, thickened skin
hypothyroidism
Parathyroid gland
Parathyroid hormone
• Major regulator of Ca++ metabolism
• Effect
– increase plasma Ca++ by
• stimulation of bone resorption
• renal tubular Ca++ reabsorption
• synthesis of 1,25-(OH)2-D3
– decrease plasma PO43-
• Regulated by plasma Ca++
concentration
RICKETS
OSTEOMALACIA:
25 YO FEMALE
Pancreas: Islets of
Langerhans
Islets of Langerhans
• Four major cell types
– Alpha (α) cells = glucagon
– Beta (β) cells = insulin
– Delta (δ) cells = somatostatin (inhibition of
insulin, glucagon, and assimilation rate of
nutrients in GI tract)
– F cells = pancreatic polypeptide (inhibits
pancreatic exocrine secretion)
Pineal gland
• Located in brain in
roof of 3rd
ventricle
Pineal gland
• Major site of melatonin synthesis
– highest levels of secretion at night
• Controversial effects
– Alleviation of jet lag after transmeridial
flights
– Antigonadal effects = inhibition of
melatonin is trigger for puberty onset
• Continuous light leads to early onset of
sexual development
Thymus
Thymus
• Location: behind manubrium of
sternum
• attains weight of approximately 40
grams at puberty, then begins to
involute
• Function: development of immune
response
• Hormone: thymosin
– T cell education
GI tract, gonads, placenta
• GI tract
• Gonads
– Androgens
– Estrogens
– Progestones
• Placenta
–
–
–
–
Estrogens
Progesterone
Human chorionic gonadotropin
somatomamotropin