Obesity

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ERM - Course overview
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Diseases/DisordersEndocrinology

• Hypothyroidism/Hyperthyroidism
• Adrenal insufficiency
• Cushing's disease
• Hyperaldosteronism
• Diabetes Insipidus
• Syndrome of Inappropiate ADH
• Hypopituitarism
• Osteoporosis/Osteopetrosis/Osteomalacia
• Primary and Secondary Hyperparathyroidism
• Hypercalcemia of Malignancy

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Diseases/DisordersMetabolism

• Diabetes mellitus, type 1 and type 2
• Hypercholesterolemia
• Hypertriglyceridemia
• Atherosclerosis
• Obesity/Overweight

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Diseases/DisordersReproduction

• Polycystic ovary syndrome
• Premature ovarian failure
• Hyperprolactinemia
• Hypothalamic Amenorrhea
• Endometriosis
• Female and Male infertility
• Preeclampsia
• Hypertension in pregnancy
• Fetal Intrauterine growth retardation

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Course Material

• ERM is primarily a lecture-based course.
  Students will be responsible for the material
  presented in lecture, the material contained in
  the syllabus, and information discussed at small
  group discussions. The course syllabus is
  required and available for purchase at the
  Bookstore.

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The Syllabus

• Illustrations that contain fine print and/or
  otherwise did not reproduce well will be posted
  on the course website for printing at one
  figure/page.
• To report errors or request clarifications
  regarding the syllabus, email Dr. Glass at
  ckg_at_ucsd.edu

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On line resources

• UCSD Access Medicine Collection
• Basic and Clinical Endocrinology, 7th Ed
• Williams Obstetrics, 22nd Ed
• The Metabolic Basis of Inherited Disease
• Harrisons Online
• http//www.accessmedicine.com/home.aspx

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Small Group Discussions / Problem-based Learning

• Small Group Discussions (SGD) will be held to
  discuss clinical cases. SGD will be organized
  into two Problem-based learning exercises and one
  focused discussion section. Attendance and
  participation in case discussions will contribute
  to approximately 10 of the overall course grade.
  All students have been assigned to a small group
  and you will find your group and the room
  assignments in the syllabus as well as on the
  website.

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Exams

• There will be three sectional 50-minute exams
  during the quarter and a two-hour final exam. The
  dates and times of the exams are indicated in the
  course schedule.
• Exam I 100 points (25-30 questions)
• Exam II 100 points (25-30 questions)
• Exam III 100 points (25-30 questions)
• Final 200 points (50-60 questions)
• Subtotal 500 points
• SGD (10) 50 points
• Total 550 points
• Students who obtain a score of 65 (358 total
  points) or better will be considered to have
  passed the course.

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Practice Exams

• Practice Exams for the first two midterm exams
  are provided in the syllabus
• Practice Exams for the third midterm and final
  are being updated to reflect new lecture material
  and will be distributed electronically later
  during the quarter.

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Core Course Committee

• Dr. Christopher Glass - Chair - ckg_at_ucsd.edu
• Dr. Jerrold Olefsky
• Dr. R. Jeffrey Chang
• Dr. Nai Wen Chi
• Sara Bakhtary, MSI
• Kathy Eng MSII

Course Coordinator

• Alexandra Howarth - azhowarth_at_ucsd.edu

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Course Lecturers

• Dr. Christopher Glass
• Dr. Jerrold Olefsky
• Dr. Wulf Palinksy
• Dr. Sunder Mudaliar
• Dr. Joseph Witztum
• Dr. Michael Gottshalk
• Dr. George Dailey
• Dr. Leonard Deftos
• Dr. Wulf Dillman

• Dr. R. Jeffrey Chang
• Dr. Sanjay Agarwal
• Dr. Robert Resnik
• Dr. Michael Kettel

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ERM Lecture 1Endocrine Control Systems

• ByChristopher K. Glass, M.D., Ph.D.

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Learning Objectives

• Students will be able to describe
• general functions of hormones
• general features of hormone interactions
• the chemical nature of hormones
• general principles of feedback relationships
• describe general categories of endocrine pathology

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ENDOCRINOLOGY

• The science and medical specialty concerned with
  the role of hormonal systems in the regulation of
  physiology (health) and pathophysiology (disease).

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Definitions

• HORMONE a molecule secreted into the circulation
  by specialized gland cells to be transported to
  target cells where it can stimulate or inhibit
  biological responses
• TARGET CELL a specialized cell that has the
  ability to bind to a particular hormone by means
  of a receptor molecule
• RECEPTOR a protein that reversibly binds a
  hormone with high affinity and specificity. The
  hormone-receptor complex can generate a signal
  that leads to biological responses in a target
  cell

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The pre-hormone era Antiquity Ancient cultures
discover the effects of castration on
secondary sexual characteristics 1849 Berthold
reports that transplantation of a
roosters testes to another part of the body
prevents the usual effects of
castration 1855-1856 Addison publishes his
monograph on the Constitu- tional and local
effects of disease of the supra-renal capsules.
Brown-Sequard performs adrenalectomies and
proves the adrenal glands are essential for
life, but concludes that they serve to detoxify
the blood. 1873 Gull describes the syndrome of
myxedema
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The Birth of Endocrinology 1889 Brown-Sequard
rejuvenates himself
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Charles-Edouard Browne-Sequard
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(No Transcript)
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The concept of a hormone is established 1891 Mur
ray successfully treats a myxedematous patient
with extracts made from the thyroid glands of
sheep. 1896-1900 Knauser and Halban
independently demonstrate that transplantation
of the ovaries prevents the effects
of castration in rabbits and guinea
pigs. 1902 Starling discovers secretin and
coins the term hormone (from the Greek
ormaw to excite). 1910 Cushing reports on
the effects of experimental hypopysectomy in
dogs and describes the infuluence of the
pituitary on gonadal function. Gudernatsch
describes the effects of thyroid extracts on
the metamorphosis of tadpoles. 1914 Kendall
crystallizes thyroxine Wilson, J.D., J Clin
Endo Metab 711403 (1990)
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Nervoussystem
Endocrine system
Regulated organor tissue
Figure 1
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Endocrine Glands
Hypothalamus
Pituitary

• The principle endocrine glands in the human
  body. Each endocrine gland secretes unique
  hormones into the circulation where they are
  transported to act on target cells to evoke
  specific biological responses that control
  homeostasis.

Thyroid
Parathyroids
Stomach /intestine
Pancreas
Adipose Tissue
Adrenals
Gonads
Figure 2
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Endocrine Gland Hormones
Function Pituitary, Anterior ACTH Adrenal
Control FSH Gonad Regulation GH Growth
Stimulation LH Gonad Regulation Prolactin Br
east Milk Production TSH Thyroid
Control Pituitary, Posterior ADH Water
Conservation Oxytocin Uterus Contraction
and Breast Milk Excretion Thyroid Thyroxine
Metabolic Rate Control Parathyroid PTH
Calcium
metabolism Gut Gut Hormones Food
Digestion Pancreas Insulin Glucose
Metabolism Glucagon Adrenals Cortisol Body
Preservation Aldosterone Salt
Conservation Epinephrine Stress
Response Ovaries Estradiol Female
Characteristics Progesterone Testes Testoster
one Male Characteristsics Adipose
Tissue Leptin Energy Homeostasis
Figure 3
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Growth anddevelopment
Reproduction
Hormones
Energy production,utilization and storage
Maintenance of internal environment
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Reproduction

• Sexual differentiation and puberty
• Gametogenesis
• Menstrual cycle
• Behavior
• Fertilization
• Pregnancy
• Lactation

Figure 4
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Growth and Development

• Growth hormone
• Insulin-like growth factors
• Thyroid hormones
• Estrogens
• androgens

Figure 5
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Energy balance

• Energy storage (Insulin)
• Fat, glycogen
• Energy expenditure
• Lipolysis
• Gluconeogenesis
• Glycogenolysis

Figure 6
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Maintenance of Internal Environment

• Electrolyte balance
• Blood pressure
• Heart rate
• Acid/base balance
• Body temperature
• Bone mass

Figure 7
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Hormone Interactions

• Testosterone
• One hormone - multiple actions
• Induction of male differentiation of the Wolffian
  ducts
• Induction of spermatogenesis
• Growth of beard and body hair
• Promotion of muscle growth

Figure 8
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Hormone Interactions

• One process - multiple hormones
• Reproduction
• Energy homeostasis
• Growth
• Multiple hormones allow
• Great range of fine tuning
• Functional redundancy

Figure 9
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The Chemical Nature of Hormones

• Peptide Hormones
• Complex polypeptides (e.g., leutinizing hormone)
• Intermediate-sized polypeptides (e.g., insuling,
  glucagon)
• Small peptides (e.g., thyrotropin releasing
  hormone)
• Dipeptides (e.g., thyroxine)
• Amino acid derivatives (e.g., catecholamines,
  histamine)

Figure 10
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Mechanism of peptide hormone action
Interstitial fluid (binding proteins and proteases
Receptor
Interstitial fluid (binding proteins and proteases
Blood vessel
Hormone
Signal Trans- duction
H
H
H
H
H
H

• Biological Response
• Proliferation
• Cytodifferentiation
• Secretion
• Contraction
• Apoptosis

Target cell
Endocrine cell
Figure 11
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The Chemical Nature of Hormones

• Non-peptide Hormones
• Steroid hormones
• Androgens
• Estrogens
• Glucocorticoids
• Mineralocorticoids
• Progestins
• Non-steroid hormones
• Vitamin D
• Retinoids
• Fatty acid derivates (e.g., prostaglandins)

Figure 12
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Classes of Receptors

• Intracellular receptors (e.g., estrogen,
  androgen, cortisol)
• Membrane receptors
• Intrinsic catalytic activity
• Protein tyrosine kinases (e.g., insulin, IGF-1)
• Kinase-linked
• JAK/STAT coupled receptors (e.g., growth
  hormone, leptin)
• G-protein linked
• cAMP/Protein kinase A (e.g., ACTH, LH)
• Ca2/protein kinase C (e.g., GnRH, PGF2a)

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Ligand-dependent signal transduction
Biological Response
Signal Transduction
HOMEOSTASIS
Figure 13
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Autocrine/Paracrine Concept

• Hormone signaling and biological responses can
  be modulated, either amplified or attenuated, by
  locally produced ligands, many of which are the
  growth factors

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GROWTH FACTOR
Blood Vessel
H
Hormone
AUTOCRINE
PARACRINE
ENDOCRINE
Figure 14
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Hormone synthesis, storage and release

• Rate of synthesis usually an important
  determinant of release
• Some peptide hormones stored to a limited extent
  in secretory granules
• Many peptide hormones require proteolytic
  processing to be biologically active
• Some hormones undergo modifications in peripheral
  tissues that are required for full biological
  activity

Figure 15
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Transport

• Water soluble hormones are transported in plasma
  in solution - no carrier proteins needed
• Less soluble hormones are carried in plasma on
  transport proteins
• General transport protein
• e.g., albumin
• Specific transport proteins
• e.g., thyroxine binding globulin, cortisol
  binding globuline

Figure 16
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The hypothalamic-pituitary endocrine gland
cascade is regulated through a process involving
negative feedback loops hormones from the
endocrine glands feedback on the hypothalamus and
pituitary to inhibit their hormone secretion.
1. Hypothalamus
2. Portal system
3. Pituitary
8. Negative Feedback Loops
4. Pituitary HORMONE
5. Endocrine gland
6. Endocrine Hormone
7. Target cells and Biological responses
Figure 17
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Biorhythms

• Minutes to hours (LH, testosterone)
• Daily (circadian rhythm of cortisol)
• Weeks (menstrual cycle)
• Seasonal (thyroid hormone)

Figure 18
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Endocrine Pathology

• Subnormal hormone production
• Hormone excess
• Resistance to hormone action
• Abnormalities of hormone transport and metabolism
• Multiple hormone abnormalities

Figure 19
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ENDOCRINOLOGY
Diabetes
Bone Fractures
Osteoporosis
PCOS
NIDDM
REPRODUCTION
Menopause
Infertilty
Heart Disease
METABOLISM
Hypercholesterolemia
Heart Disease
Obesity
Figure 20