Title: Obesity
1ERM - Course overview
2Diseases/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
3Diseases/DisordersMetabolism
- Diabetes mellitus, type 1 and type 2
- Hypercholesterolemia
- Hypertriglyceridemia
- Atherosclerosis
- Obesity/Overweight
4Diseases/DisordersReproduction
- Polycystic ovary syndrome
- Premature ovarian failure
- Hyperprolactinemia
- Hypothalamic Amenorrhea
- Endometriosis
- Female and Male infertility
- Preeclampsia
- Hypertension in pregnancy
- Fetal Intrauterine growth retardation
5Course 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.
6The 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
7On 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
8Small 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.
9Exams
- 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.
10Practice 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.
11Core 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
12Course 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
13ERM Lecture 1Endocrine Control Systems
- ByChristopher K. Glass, M.D., Ph.D.
14Learning 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
15ENDOCRINOLOGY
- The science and medical specialty concerned with
the role of hormonal systems in the regulation of
physiology (health) and pathophysiology (disease).
16Definitions
- 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
17The 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
18The Birth of Endocrinology 1889 Brown-Sequard
rejuvenates himself
19Charles-Edouard Browne-Sequard
20(No Transcript)
21The 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)
22Nervoussystem
Endocrine system
Regulated organor tissue
Figure 1
23Endocrine 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
25Growth anddevelopment
Reproduction
Hormones
Energy production,utilization and storage
Maintenance of internal environment
26Reproduction
- Sexual differentiation and puberty
- Gametogenesis
- Menstrual cycle
- Behavior
- Fertilization
- Pregnancy
- Lactation
Figure 4
27Growth and Development
- Growth hormone
- Insulin-like growth factors
- Thyroid hormones
- Estrogens
- androgens
Figure 5
28Energy balance
- Energy storage (Insulin)
- Fat, glycogen
- Energy expenditure
- Lipolysis
- Gluconeogenesis
- Glycogenolysis
Figure 6
29Maintenance of Internal Environment
- Electrolyte balance
- Blood pressure
- Heart rate
- Acid/base balance
- Body temperature
- Bone mass
Figure 7
30Hormone 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
31Hormone Interactions
- One process - multiple hormones
- Reproduction
- Energy homeostasis
- Growth
- Multiple hormones allow
- Great range of fine tuning
- Functional redundancy
Figure 9
32The 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
33Mechanism 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
34The 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
35Classes 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)
36Ligand-dependent signal transduction
Biological Response
Signal Transduction
HOMEOSTASIS
Figure 13
37Autocrine/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
38GROWTH FACTOR
Blood Vessel
H
Hormone
AUTOCRINE
PARACRINE
ENDOCRINE
Figure 14
39Hormone 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
40Transport
- 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
41The 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
42Biorhythms
- Minutes to hours (LH, testosterone)
- Daily (circadian rhythm of cortisol)
- Weeks (menstrual cycle)
- Seasonal (thyroid hormone)
Figure 18
43Endocrine Pathology
- Subnormal hormone production
- Hormone excess
- Resistance to hormone action
- Abnormalities of hormone transport and metabolism
- Multiple hormone abnormalities
Figure 19
44ENDOCRINOLOGY
Diabetes
Bone Fractures
Osteoporosis
PCOS
NIDDM
REPRODUCTION
Menopause
Infertilty
Heart Disease
METABOLISM
Hypercholesterolemia
Heart Disease
Obesity
Figure 20