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Obesity

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Title: Obesity


1
ERM - Course overview
2
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

3
Diseases/DisordersMetabolism
  • Diabetes mellitus, type 1 and type 2
  • Hypercholesterolemia
  • Hypertriglyceridemia
  • Atherosclerosis
  • Obesity/Overweight

4
Diseases/DisordersReproduction
  • Polycystic ovary syndrome
  • Premature ovarian failure
  • Hyperprolactinemia
  • Hypothalamic Amenorrhea
  • Endometriosis
  • Female and Male infertility
  • Preeclampsia
  • Hypertension in pregnancy
  • Fetal Intrauterine growth retardation

5
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.

6
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

7
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

8
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.

9
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.

10
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.

11
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

12
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

13
ERM Lecture 1Endocrine Control Systems
  • ByChristopher K. Glass, M.D., Ph.D.

14
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

15
ENDOCRINOLOGY
  • The science and medical specialty concerned with
    the role of hormonal systems in the regulation of
    physiology (health) and pathophysiology (disease).

16
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

17
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
18
The Birth of Endocrinology 1889 Brown-Sequard
rejuvenates himself
19

Charles-Edouard Browne-Sequard
20
(No Transcript)
21
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)
22
Nervoussystem
Endocrine system
Regulated organor tissue
Figure 1
23
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
24
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
25
Growth anddevelopment
Reproduction
Hormones
Energy production,utilization and storage
Maintenance of internal environment
26
Reproduction
  • Sexual differentiation and puberty
  • Gametogenesis
  • Menstrual cycle
  • Behavior
  • Fertilization
  • Pregnancy
  • Lactation

Figure 4
27
Growth and Development
  • Growth hormone
  • Insulin-like growth factors
  • Thyroid hormones
  • Estrogens
  • androgens

Figure 5
28
Energy balance
  • Energy storage (Insulin)
  • Fat, glycogen
  • Energy expenditure
  • Lipolysis
  • Gluconeogenesis
  • Glycogenolysis

Figure 6
29
Maintenance of Internal Environment
  • Electrolyte balance
  • Blood pressure
  • Heart rate
  • Acid/base balance
  • Body temperature
  • Bone mass

Figure 7
30
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
31
Hormone Interactions
  • One process - multiple hormones
  • Reproduction
  • Energy homeostasis
  • Growth
  • Multiple hormones allow
  • Great range of fine tuning
  • Functional redundancy

Figure 9
32
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
33
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
34
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
35
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)

36
Ligand-dependent signal transduction
Biological Response
Signal Transduction
HOMEOSTASIS
Figure 13
37
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

38
GROWTH FACTOR
Blood Vessel
H
Hormone
AUTOCRINE
PARACRINE
ENDOCRINE
Figure 14
39
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
40
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
41
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
42
Biorhythms
  • Minutes to hours (LH, testosterone)
  • Daily (circadian rhythm of cortisol)
  • Weeks (menstrual cycle)
  • Seasonal (thyroid hormone)

Figure 18
43
Endocrine Pathology
  • Subnormal hormone production
  • Hormone excess
  • Resistance to hormone action
  • Abnormalities of hormone transport and metabolism
  • Multiple hormone abnormalities

Figure 19
44
ENDOCRINOLOGY
Diabetes
Bone Fractures
Osteoporosis
PCOS
NIDDM
REPRODUCTION
Menopause
Infertilty
Heart Disease
METABOLISM
Hypercholesterolemia
Heart Disease
Obesity
Figure 20
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