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THIRD EDITION
HUMAN PHYSIOLOGY
AN INTEGRATED APPROACH
Dee Unglaub Silverthorn, Ph.D.
Chapter 7
The Endocrine System
PowerPoint® Lecture Slide Presentation by
Dr. Howard D. Booth, Professor of Biology, Eastern Michigan University
Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings
About this Chapter
• Expand on integration of chemical and nervous
coordination
• Form and function of key endocrine glands
• Classification, structure and synthesis of
hormones
• Pathways of nervous to endocrine regulation
• How target cells/tissues are impacted
• Some pathologies of the endocrine system
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Summary of the Endocrine System
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Figure 7-2-1: ANATOMY SUMMARY: Hormones
Summary of the Endocrine System
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Figure 7-2-2: ANATOMY SUMMARY: Hormones
Summary of the Endocrine System
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Figure 7-2-3: ANATOMY SUMMARY: Hormones
Mechanism of Hormone Action
• Hormones produce one or more of the following
cellular changes in target cells
• Alter plasma membrane permeability
• Stimulate protein synthesis
• Activate or deactivate enzyme systems
• Induce secretory activity
• Stimulate mitosis
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Chemical Regulating Systems: Overview
• Pheromones: organism to organism
communication
• Hormones: cell to cell communication molecules
• Made in gland(s) or cells
• Transported by blood
• Distant target tissue receptors
• Activates physiological response
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Protein and Polypeptide Hormones:
Synthesis and Release
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Figure 7-3: Peptide hormone synthesis, packaging, and release
Hormones
• Three types
• Proteins
• Glycoproteins
• Small peptides
• Large proteins
• Lipids
• Cholesterol derivatives
• Eicosanoids
• Amino acid derivatives
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Amino Acid-Based Hormone Action:
cAMP Second Messenger
• Hormone (first messenger) binds to its receptor,
which then binds to a G protein
• The G protein is then activated as it binds GTP,
displacing GDP
• Activated G protein activates the effector enzyme
adenylate cyclase
• Adenylate cyclase generates cAMP (second
messenger) from ATP
• cAMP activates protein kinases, which then cause
cellular effects
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Amino Acid-Based Hormone Action:
PIP-Calcium
• Hormone binds to the receptor and activates
G protein
• G protein binds and activates a phospholipase
enzyme
• Phospholipase splits the phospholipid PIP2 into
diacylglycerol (DAG) and IP3 (both act as second
messengers)
• DAG activates protein kinases; IP3 triggers release
of Ca2+ stores
• Ca2+ (third messenger) alters cellular responses
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Protein and Polypeptide Hormone Receptors
• Surface receptor
• Hormone binds
• Transduction
• Enzyme activation
• Open channels
• Second messenger
systems
• Synthesis
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Figure 7-5: Membrane receptors for peptide hormones
Amine Hormone Structures and Functions
• Made of 1-2 amino acids, derived from tyrosine or
tryptophan
• Receptors
• Surface
• Intracellular
• Small size, OH group
• Benzine ring
• Examples
• Thyroxin
• Epinephrine
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Amine Hormone Structures and Functions
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Figure 7-8: Tyrosine-derived amine hormones
Steroid Hormones: Structure and Action
• From cholesterol, lipophilic, enter target cell,
• Cytoplasmic or nuclear receptors (mostly)
• Activate DNA for protein synthesis
• Slower acting, longer half-life
• Examples: cortisol, estrogen & testosterone
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Steroid Hormones
• Steroid hormones and thyroid hormone diffuse easily
into their target cells
• Once inside, they bind and activate a specific
intracellular receptor
• The hormone-receptor complex travels to the nucleus
and binds a DNA-associated receptor protein
• This interaction prompts DNA transcription to produce
mRNA
• The mRNA is translated into proteins, which bring
about a cellular effect
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Steroid Hormones: Structure and Action
Figure 7-7: Steroid hormone action
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Steroid Hormones
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Figure 16..3
Steroid Hormones: Structure and Action
Figure 7-6: Steroid hormones are derived from cholesterol
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Target Cell Specificity
• Hormones circulate to all tissues but only activate
cells referred to as target cells
• Target cells must have specific receptors to which
the hormone binds
• These receptors may be intracellular or located on
the plasma membrane
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Target Cell Activation
• Target cell activation depends on three factors
• Blood levels of the hormone
• Relative number of receptors on the target cell
• The affinity of those receptors for the hormone
• Up-regulation – target cells form more receptors
in response to the hormone
• Down-regulation – target cells lose receptors in
response to the hormone
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Hormone Concentrations in the Blood
• Hormones circulate in the blood in two forms –
free or bound
• Steroids and thyroid hormone are attached to
plasma proteins
• All others are unencumbered
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Hormone Concentrations in the Blood
• Concentrations of circulating hormone reflect:
• Rate of release
• Speed of inactivation and removal from the
body
• Hormones are removed from the blood by:
• Degrading enzymes
• The kidneys
• Liver enzyme systems
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Control of Hormone Release
• Blood levels of hormones:
• Are controlled by negative feedback systems
• Vary only within a narrow desirable range
• Hormones are synthesized and released in
response to humoral, neural, and hormonal
stimuli
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Endocrine Reflex Pathways: Overview
• Stimulus
• Afferent signal
• Integration
• Efferent signal (the hormone)
• Physiological action
• Negative feedback
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Multiple Stimuli for Hormone Release:
Nervous & Endocrine
• Stimuli
• Stretch
• Glucose
• Insulin levels
• Reflex
• Lower blood glucose
• Reduces stimulus
• Reduces insulin release
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Endocrine Reflex Pathways: Overview
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Figure 7-9: Hormones may have multiple stimuli for their release
Neurohormones: secreted into the Blood by Neurons
• Adrenal Medulla–catecholamines
• Hypothalamus to:
• Anterior pituitary
• Trophic Hs
• Growth H.
• Prolactin
• Posterior pituitary
• Vasopressin
• Oxytocin
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Neurohormones: secreted into the Blood by Neurons
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Figure 7-12: Synthesis, storage, and release of posterior pituitary hormones
Pituitary-Hypothalamic Relationships:
Posterior Lobe
• The posterior lobe is a downgrowth of
hypothalamic neural tissue
• Has a neural connection with the hypothalamus
(hypothalamic-hypophyseal tract)
• Nuclei of the hypothalamus synthesize oxytocin
and antidiuretic hormone (ADH)
• These hormones are transported to the posterior
pituitary
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Major Endocrine Organs: Pituitary (Hypophysis)
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Figure 16.5
The Posterior Pituitary and Hypothalamic
Hormones
• Posterior pituitary – made of axons of
hypothalamic neurons, stores antidiuretic
hormone (ADH) and oxytocin
• ADH and oxytocin are synthesized in the
hypothalamus
• ADH influences water balance
• Oxytocin stimulates smooth muscle contraction in
breasts and uterus
• Both use PIP-calcium second-messenger
mechanism
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Oxytocin
• Oxytocin is a strong stimulant of uterine
contraction
• Regulated by a positive feedback mechanism to
oxytocin in the blood
• This leads to increased intensity of uterine
contractions, ending in birth
• Oxytocin triggers milk ejection (“letdown” reflex)
in women producing milk
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Oxytocin
• Synthetic and natural oxytocic drugs are used to
induce or hasten labor
• Plays a role in sexual arousal and satisfaction in
males and nonlactating females
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Antidiuretic Hormone (ADH)
• ADH helps to avoid dehydration or water overload
• Prevents urine formation
• Osmoreceptors monitor the solute concentration of
the blood
• With high solutes, ADH is synthesized and released,
thus preserving water
• With low solutes, ADH is not released, thus causing
water loss from the body
• Alcohol inhibits ADH release and causes copious
urine output
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Pituitary-Hypothalamic Relationships:
Anterior Lobe
• The anterior lobe of the pituitary is an
outpocketing of the oral mucosa
• There is no direct neural contact with the
hypothalamus
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Endocrine Control: Three Levels of Integration
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Figure 7-13: Hormones of the hypothalamic-anterior pituitary pathway
Pituitary-Hypothalamic Relationships:
Anterior Lobe
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Adenohypophyseal Hormones
• The six hormones of the adenohypophysis:
• Are abbreviated as GH, TSH, ACTH, FSH, LH,
and PRL
• Regulate the activity of other endocrine glands
• In addition, pro-opiomelanocortin (POMC):
• Has been isolated from the pituitary
• Is enzymatically split into ACTH, beta
endorphin, and several Melanocyte Stimulating
Hormones and Lipotropins
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Diagram of the POMC Gene
• Pro-opiomelanocortin (POMC) is a precursor
polypeptide with 241 amino acid residues. POMC is
synthesized from the 285-amino-acid-long polypeptide
precursor pre-pro-opiomelanocortin (pre-POMC), by
the removal of a 44-amino-acid-long signal peptide
sequence during translation.
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Activity of the Adenophypophysis
• The hypothalamus sends a chemical stimulus to
the anterior pituitary
• Releasing hormones stimulate the synthesis
and release of hormones
• Inhibiting hormones shut off the synthesis and
release of hormones
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Activity of the Anterior Pituitary (Adenophypophysis)
• The tropic hormones that are released are:
• Thyroid-stimulating hormone (TSH),
Thyrotropin
• Adrenocorticotropic hormone (ACTH),
Corticotropin
• Follicle-stimulating hormone (FSH), a
Gonadotropin
• Luteinizing hormone (LH), a Gonadotropin
• Growth Hormone (GH), Somatotropin
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Endocrine Control: Three Levels of Integration
• Hypothalamic stimulation–from CNS
• Pituitary stimulation–from hypothalamic trophic
Hs
• Endocrine gland stimulation–from pituitary
trophic Hs
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Negative Feedback Controls:
Long & Short Loop Reflexes
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Figure 7-14: Negative
feedback loops in the
hypothalamicanterior
pituitary pathway
Negative Feedback Controls:
Long & Short Loop Reflexes
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Figure 7-15: Control pathway for cortisol secretion
Thyroid Gland
• The largest endocrine gland, located in the
anterior neck, consists of two lateral lobes
connected by a median tissue mass called the
isthmus
• Composed of follicles that produce the
glycoprotein thyroglobulin
• Colloid (thyroglobulin + iodine) fills the lumen of
the follicles and is the precursor of thyroid
hormone
• Other endocrine cells, the parafollicular cells,
produce the hormone calcitonin
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Thyroid Gland
Figure 16.7
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Thyroid Hormone
• Thyroid hormone – the body’s major metabolic
hormone
• Consists of two closely related iodine-containing
compounds
• T4 – thyroxine; has two tyrosine molecules plus
four bound iodine atoms
• T3 – triiodothyronine; has two tyrosines with
three bound iodine atoms
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Effects of Thyroid Hormone
• TH is concerned with:
• Glucose oxidation
• Increasing metabolic rate
• Heat production
• TH plays a role in:
• Maintaining blood pressure
• Regulating tissue growth
• Developing skeletal and nervous systems
• Maturation and reproductive capabilities
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Synthesis of Thyroid Hormone
• Thyroglobulin is synthesized and discharged into
the lumen
• Iodides (I–) are actively taken into the cell, oxidized
to iodine (I2), and released into the lumen
• Iodine attaches to tyrosine, mediated by peroxidase
enzymes, forming T1 (monoiodotyrosine, or MIT),
and T2 (diiodotyrosine, or DIT)
• Iodinated tyrosines link together to form T3 and T4
• Colloid is then endocytosed and combined with a
lysosome, where T3 and T4 are cleaved and diffuse
into the bloodstream
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Synthesis of Thyroid Hormone
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Figure 16.8
Transport and Regulation of TH
• T4 and T3 bind to thyroxine-binding globulins
(TBGs) produced by the liver
• Both bind to target receptors, but T3 is ten times
more active than T4
• Peripheral tissues convert T4 to T3
• Mechanisms of activity are similar to steroids
• Regulation is by negative feedback
• Hypothalamic thyrotropin-releasing hormone
(TRH) can overcome the negative feedback
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Growth Hormone (GH) or Somatotropin
• Produced by somatotropic cells of the anterior
lobe that:
• Stimulate most cells, but target bone and
skeletal muscle
• Promote protein synthesis and encourage the
use of fats for fuel
• Most effects are mediated indirectly by
somatomedins
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Growth Hormone (GH)
• Antagonistic hypothalamic hormones regulate GH
• Growth hormone–releasing hormone (GHRH)
stimulates GH release- aka Somatoliberin or
Somatocrinin
• Growth hormone–inhibiting hormone (GHIH)
inhibits GH release- aka Somatostatin
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Metabolic Action of Growth Hormone
• GH stimulates liver, skeletal muscle, bone, and
cartilage to produce insulin-like growth factors
• Direct action promotes lipolysis and inhibits
glucose uptake
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Metabolic Action of Growth Hormone
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Figure 16.6
Multiple Hormones Can Target a Cell/Tissue
• Growth H
• Somatomedins
• Thyroxin
• All have receptors
on many tissues
• Stimulate
pathways for
growth
Figure 7-17: A complex endocrine pathway
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More Impacts on Target Cells
• Synergism: multiple stimuli more than additive
• Cortisol +5
• Glucagon +10
• Epinephrine +20 (added = +35)
• Synergistic effect + 140
• Antagonism: Two hormones opposing each other
in their function, ie. glucagon opposes insulin
• Permissiveness: need 2nd hormone to get full
expression, ie. one hormone enhances target
organ’s response to a second hormone that is
secreted later
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Permissive Actions of Thyroid Hormone
• Thyroxin (T4) is needed for the function of
epinephrine in fatty acid release since
Thyroxin induces synthesis of epinephrine
receptor
• Thyroid hormone is also
Permissive (needed) for GH secretion and action
Permissive (needed) for development of central
nervous system
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More Impacts on Target Cells
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Figure 7-18: Synergism
Pathologies: Over or Under Production
• "no bad hormones – just too much or too little"
• Exogenous medication
• Replaces & exceeds normal
• Cause atrophy of gland
• Hypersecretion: too much
• Tumors or cancer
• Grave's disease- thyroxin
• Hyposecretion: too little
• Goiter – thyroxin
• Diabetes – insulin
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Thyroid Stimulating Hormone (Thyrotropin)
• Tropic hormone that stimulates the normal
development and secretory activity of the thyroid
gland
• Triggered by hypothalamic peptide thyrotropinreleasing hormone (TRH)
• Rising blood levels of thyroid hormones act on the
pituitary and hypothalamus to block the release of
TSH
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Adrenocorticotropic Hormone (Corticotropin)
• Stimulates the adrenal cortex to release
corticosteroids
• Triggered by hypothalamic corticotropinreleasing hormone (CRH) in a daily rhythm
• Internal and external factors such as fever,
hypoglycemia, and stressors can trigger the
release of CRH
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Adrenal (Suprarenal) Glands
• Adrenal glands – paired, pyramid-shaped organs
atop the kidneys
• Structurally and functionally, they are two glands
in one
• Adrenal medulla – nervous tissue that acts as
part of the SNS
• Adrenal cortex – glandular tissue derived from
embryonic mesoderm
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Adrenal Cortex
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Figure 16.12a
Adrenal Cortex
• Synthesizes and releases steroid hormones called
corticosteroids
• Different corticosteroids are produced in each of
the three layers
• Zona glomerulosa – mineralocorticoids
(chiefly aldosterone)
• Zona fasciculata – glucocorticoids
(chiefly cortisol)
• Zona reticularis – gonadocorticoids
(chiefly androgens)
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Mineralocorticoids
• Regulate the electrolyte concentrations of
extracellular fluids
• Aldosterone – most important mineralocorticoid
• Maintains Na+ balance by reducing excretion of
sodium from the body
• Stimulates reabsorption of Na+ by the kidneys
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Glucocorticoids (Cortisol)
• Help the body resist stress by:
• Keeping blood sugar levels relatively constant
• Maintaining blood volume and preventing
water shift into tissue
• Cortisol provokes:
• Gluconeogenesis (formation of glucose from
noncarbohydrates)
• Rises in blood glucose, fatty acids, and amino
acids
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Excessive Levels of Glucocorticoids
• Excessive levels of glucocorticoids:
• Depress cartilage and bone formation
• Inhibit inflammation
• Depress the immune system
• Promote changes in cardiovascular, neural, and
gastrointestinal function
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Gonadocorticoids (Sex Hormones)
• Most gonadocorticoids secreted are androgens
(male sex hormones), and the most important one
is testosterone
• Androgens contribute to:
• The onset of puberty
• The appearance of secondary sex
characteristics
• Sex drive in females
• Androgens can be converted into estrogens after
menopause
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Adrenal Medulla
• Made up of chromaffin cells that secrete
epinephrine and norepinephrine
• Secretion of these hormones causes:
• Blood glucose levels to rise
• Blood vessels to constrict
• The heart to beat faster
• Blood to be diverted to the brain, heart, and
skeletal muscle
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Adrenal Medulla
• Epinephrine is the more potent stimulator of the
heart and metabolic activities
• Norepinephrine is more influential on peripheral
vasoconstriction and blood pressure
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Stress and the Adrenal Gland
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Figure 16.15
Symptoms of Cushing’s
•
Facial redness
•
Rounding of the face (moon face)
•
Unexplained weight gain around belly
•
Buffalo hump, or hump on back of neck
•
Pink or purple stretch marks
•
Thicker or more visible body and facial hair
•
Acne
•
Muscle weakness
•
Extreme fatigue
•
Thin and fragile skin that bruises easily
•
Depression, anxiety and irritability
•
Slow healing of cuts, insect bites and infections
•
Bone thinning
•
Recurrent infections
•
Sleep disturbances, night sweats, awake at midnight or 4 am
•
High blood pressure
•
Diabetes mellitus
•
Irregular or absent menstrual periods in females
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Cushing’s Syndrome
Clinical features
•
•
General
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Central obesity
Proximal muscle weakness
HTN
Headaches
Dermatologic
•
•
•
•
•
•
Wide purple striae
Spontaneous ecchymoses
Facial plethora
Hyperpigmentation
Acne, hirsutism
Fungal skin infections
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Endocrine/Metabolic
•
Hypokalemic alkalosis
Hypokalemia
Osteopenia
Hypogonadism
Glucose intolerance
Hyperlipidemia
Hyperhomocysteinemia
Kidney stones
Polyuria
Hypercoagulability
Neuropsychiatric
•
•
•
Insomnia
Depression, frank psychosis
Impaired cognition and short-term
memory
Cushing’s Syndrome
Clinical features
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Presentation
Weight Gain
Glucose Intolerance
HTN
Hypokalemia
Infections
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Pathologies: Over or Under Production
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Figure 7-19: Negative feedback by exogenous cortisol
Gonadotropins
• Gonadotropins – follicle-stimulating hormone
(FSH) and luteinizing hormone (LH)
• Regulate the function of the ovaries and testes
• FSH stimulates gamete (egg or sperm)
production
• Absent from the blood in prepubertal boys and
girls
• Triggered by the hypothalamic gonadotropinreleasing hormone (GnRH) during and after
puberty
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Gonads: Female
• Paired ovaries in the abdominopelvic cavity
produce estrogens and progesterone
• They are responsible for:
• Maturation of the reproductive organs
• Appearance of secondary sexual characteristics
• Breast development and cyclic changes in the
uterine mucosa
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Functions of Gonadotropins
• In females
• LH works with FSH to cause maturation of the
ovarian follicle
• LH works alone to trigger ovulation (expulsion
of the egg from the follicle)
• LH promotes synthesis and release of estrogens
and progesterone
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Gonads: Male
• Testes located in an extra-abdominal sac
(scrotum) produce testosterone
• Testosterone:
• Initiates maturation of male reproductive
organs
• Causes appearance of secondary sexual
characteristics and sex drive
• Is necessary for sperm production
• Maintains sex organs in their functional state
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Functions of Gonadotropins
• In males
• LH stimulates interstitial cells of the testes to
produce testosterone
• LH is also referred to as interstitial cellstimulating hormone (ICSH)
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Prolactin (PRL)
• In females, stimulates milk production by the
breasts
• Triggered by the hypothalamic prolactin-releasing
hormone (PRH)
• Inhibited by prolactin-inhibiting hormone (PIH)
• Blood levels rise toward the end of pregnancy
• Suckling stimulates PRH release and encourages
continued milk production
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Pathologies: Due to Receptors
• Downregulation – hyperinsulinemia
• Transduction abnormalities
• Testicular feminization syndrome: Cause by a
defective receptor for Testosterone
• Pseudohypoparathyroidism: caused by
defective G Protein Signal Transduction
• Abnormalities of control mechanisms
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Pathologies: Primary and Secondary Hypersecretion
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Figure 7-20: Primary and secondary hypersecretion of cortisol
Pineal Gland
• Small gland hanging from the roof of the third
ventricle of the brain
• Secretory product is melatonin
• Melatonin is involved with:
• Day/night cycles
• Physiological processes that show rhythmic
variations (body temperature, sleep, appetite)
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Pineal Gland and Melatonin
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Figure 7-22-1: The pineal gland
Circadian Clock
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Pineal Gland and Melatonin
• Melatonin: Influences body clock & antioxidant
activity
• Other roles need research: SAD (Seasonal
Affective Disorder) & sexual behavior (?)
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Pineal Gland and Melatonin
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Figure 7-22-2: The pineal gland
Recommendations for Jet Lag
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Summary
• Endocrine glands throughout body are key to
chemical integration and homeostasis
• Protein, polypeptide, amine and a few steroid
hormones are plasma soluble and target membrane
• Surface receptors transduce signals into cell and
activate via second messengers
• Most steroid and some amine hormones are
lipophilic, can pass into cell, bind on cytoplasmic
or nuclear receptors and activate DNA for protein
synthesis
• Hypothalamus, pituitary trophic hormone
pathways coordinate endocrine regulation
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