Transcript I-Introduction

MCB 3210/5210 Molecular Endocrinology (I)
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Propfessors Thomas T. Chen, Office: TLS Rm 413A; Tel: 860-486-5481; Email: [email protected]
Professor Jianjun Sun, Office: PBB 117A; Tel: 860-486-5481; E-mail:
[email protected]
Office hour: Tue 1:00-3:00 p.m. or by appointment
Class Meeting Time: Tue and Thu 11:00 a.m. to 12:15 p.m. in TLS
Rm 263
Text Book:
 Recommended textbook: Vertebrate Endocrinology 5th ed. by David
O. Norris
 Some original papers will be assigned in class for additional reading
Course Grade:
 For MCB 3210: average of two exams (Mid-term and Final)
 For MCB 5210: average of two exams (70%) + one in class
presentation and a 20-page essay on the same topic of presentation
(30%)
MCB 3210/5210 Molecular Endocrinology (II)
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Two Lecture Exams:
 Exam I: Tue, October 14th
 Exam II: During the final exam week (to be announced)
Duration of lecture per period: 75 min
Exam questions will consist of short or long answers
and problem solving questions. Materials will be
taken from lecture materials and the assigned reading
materials in the textbook and original research papers
Lecture materials will be posted on the website. Each
student is responsible for printing out the materials
from the website and bring to class for the lectures
Class website:
http://www.sp.uconn.edu/~ttc02001/MCB3210-5210/
An extra credit essay paper (20 pages, double-space)
I. Introduction
Molecular Endocrinology
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Molecular Endocrinology: Studies of structures, synthesis
and actions of hormones (bioregulators) at cellular and
molecular levels
Definition of hormone:
 Classic definition: Hormones are chemical substances produced by
specialized tissues (endocrine glands) and secreted into the blood
stream, where they are carried to target organs
 Broader definition: Hormone are chemicals, non-nutrients,
intracellular messengers that are effective at micromolar
concentrations or less. In other words hormones are chemical
substances that carry information between two or more cell types.
They are also called as “bioregulators”
Discrepancies between the classic and the broader
definitions:
 Specialized tissue for hormone synthesis (vs. multiple tissues)
 Blood for hormone distribution (vs. blood, intercellular fluid)
 A separate organ for hormone action (vs. multiple target tissues)
Origins of Chemical A. Early cells living in the primordial
seas developed “receptors” for
Communication
recognition of water-soluble toxins,
nutrients and internal “receptors” for
lipids that could readily pass through
the membrane. Some of these
“receptors” transferred these
molecules into the cell for metabolism
or detoxification
B. Besides accumulating molecules
intracellularly, early cells also
released special molecules into the
environment that were detected via
receptors on other cells and served as
a mechanism for cell-to-cell
communication. Various features of
these ancient mechanisms for
accumulation, detoxification,
metabolism, and chemical
communication have persisted in one
form or another in all living cells to
this day
Categoreies of
Bioregulators
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Chemical communication
involves:
1. Neurocrines, including
neurotransmitters or
neuromodulators
2. Neurohormones
3. Hormones
4. Autocrine/paracrine
regulators
5. Ectohormones
(semiochemicals)
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The liver and kidney serve
as major sites for the
metabolism and excretion
of bioregulators.
Chemical Bioregulation
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Bioregulation is
defined as
secretion of:
 The
endocrine
system
 The nervous
system
 The immune
system
 Virtually all
cells in the
body that use
chemicals to
communicate
with one
another
Bioregulators
Types of Regulators
Some
Mammalian
Neurocrine
Regulators
The separation of
neural and
endocrine
systems have
become more
blurred when it
was learned that
some established
hormones also
were produced
within the nervous
system where
they function as
neurotransmitters
or neuromodulators
Some Important Terms
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Endocrine glands
Hormones
Receptors
Hormone-receptor complex
Bioregulation, bioregulators
Environmental endocrinology
Endocrine disruption, endocrine disrupting
chemicals (EDCs), endocrine active chemicals
(EACs)
Diethylstilbestrol (DES), DDT, polychlorinated
biphenyls (PCBs) (examples of EDCs) are known
endocrine disruptors
Some Terms
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Cytocrine: local hormones including growth factors,
mitogenic regulators, embryonic tissue-inducing
substances, secretogogues (secretion-enhancing
factors), inhibitors and immune regulators. These
factors can act as autocrines or paracrines
Intracrines: Chemical messengers (secondary
messengers or transcription factors) that govern
intracellular events
Endocrines: Hormones
Ectohormones (semiochemicals): Chemical messengers
secreted from one organism into the environment that
affect the physiology or behavior of another organism.
Example: pheromones (primer pheromone, releaser
pheromone), Allelomes (allomones and kairmones)
Chemical Nature of Bioregulators
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Peptide and protein hormones (most abundant):
thyrotropin releasing hormone, GnRH, GH, PRL,
insulin etc.
Amino acid derivatives: thyroid hormone,
epinephrine
Steriod hormones: testostrone, estrogen, cotisone
etc.
Lipids: prostaglandin, retinoic acid etc.
Nucleotides: cAMP, cytokinins, 1-methylalanine etc.
Oligosaccharides: a-1,4-oligogalacturonide
Gases: CO, ethylene etc
Structural Diversity of Hormones
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A. Thyrotropin
releasing
hormone
B. Epinephrine
C. Cortisol
D. Prostaglandin
E. Plated
activating factor
F. Zeatin (a
cytokinin)
G. a-1,4oligogalacturonid
e (an elicitor)
H. ethylene
Functional Conceptualization of the
Endocrine System
Organization of Bioregulator Systems
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Neuroendocrine system: Brain (hypothalomus) and
pituitary gland (producing tropic hormons and other
hormones)
Classical endocrine glands: thyroid gland, adrenal
glands, gonads, and liver
Independent endocrine glands: parathyroid glands,
thymus, endocrine pancreas, organs of the
gastrointestinal tract, pineal gland and the kidney
Tropic hormones: Hormones secreted by
hypothalamus that regulate the secretion of peptide or
protein hormone from pituitary glands, thyroid glands,
adrenal cortex, gonads and liver
Table 1-3 in the textbook and the following few slides
list many of these hormones. Please read.
Major Mammalian Endocrine Secretions (I)
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Hypothalamus:
 producing hypothalamus releasing neurohormones such as
TRH, GnRH, CRH, GHRH, GH-RIH, PRIH, PRH, MRIH, MRH
 Producing other neurohormones such as AVP, OXY,
Endophines/enkephalins
Anterior pituitary:
 Producing glycoprotein tropic hormones such as TSH, LH
(leuteinizing hyormone), and FSH
 Producing nonglycoprotein tropic hormone such as GH, PRL,
ATCH, and melanotropin (MSH)
Thyroid gland:
 Producing thyroid hormones (T3 and T4) and calcitonin
Gonads:
 Ovary: producing estrogens, progestrone and inhibin
 Testis: producing testostrone and other androgens,a d inhibin
Major Mammalian Endocrine Secretions (II)
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Adrenal glands:
 Adrenal cortex: producing aldosterone and corticosterone/
cortisol
 Adrenal mediulli: producing epinephrine/norepinephine
Parathyroid gland:
 Producing PTH
Endocrine pancreas:
 Producing insulin, glucogon, pancreatic polypeptide & GH-RIH
Liver:
 IGF-I and IGF-II
Adipose tissue:
 Producing leptin
Kidney:
 Producing erythropoietin, renin, and 1,25-dihydrocholecalciferol
Major Mammalian Endocrine Secretions (III)
 Gastrointestinal system:
 Stomach: producing gastrin and ghrelin
 Small intestine: producing secretin, cholecystokinin, gastrinrteleasing peptide, gastric inhibitory peptide, motilin,
somatostatin and vasoactive intestinal peptide
 Pineal gland:
 producing melatonin
 Immune system
 Thymus: producing thymosins
 Macrophages/lymphocytes: producing interleukin 1 and
lnterleukin 2
Morphological Features of Bioregulator Secreting Cells
Steroid secreting cells
Growth hormone secreting cells
Organization of Endocrine Cells
(A) Cells secreting growth hormone (orange) and gonadotropins (blue) in a
pituitary gland; (B) Islet of insulin secreting cells (arrow) embedded within the
darker stained exocrine pancreas; (C) Follicles from a thyroid gland showing
a thin epithelium and pink colloid filling the lumen of the follicle. (D) Isolated
clusters of testosterone secreting interstitial cells (arrow) located between
seminiferous tubules in a testis.
Homeostasis
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Defined by Walter B. Cannon: Balanced physiological
systems operating in the organism to maintain a
dynamic equilibrium (a relatively constant steady
state) maintained within certain tolerable limits
This concept was originally used to describe the
maintenance of blood parameters such as osmotic
pressure, volume, hydrostatic pressure and levels of
various simple chemicals Ca++, Na+ and glucose
It can be expanded to include all manner of
physiological bioregulation at the level of organism
and at the levels of molecular and cellular levels
Hormonal Control Systems
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Negative feedback control: Rising levels of a
hormone shuts down the production of the hormone
so that its level can be maintained. Example: cortisol
inhibits hypothalamus to produce CRF to control
adrenal cortex to produce cortisol
Positive feedback control: Rising hormone levels
stimulates further production of the hormone.
Example: production of oxytocin near parturition
Cycle-dependent feedback control: Nagative and
positive controls function together. Example:
estrogen negative feedback control hypothalamus to
produce more estrogen in nonmidcycle, but at
midcycle, estrogen positive regulate hypothalamus
to produce more estrogen to induce a surge of
luteinizing hormone leading to ovulation
Feedback
Regulation of
Hormone
Secretion
A. Negative Feedback
B. Positive Feedback
C. Cycle-dependent
Feedback
Life History of a Hormone
Liver and kidney are major sites of hormone metabolism and excretion
Endocrine Disruption of Homeostasis
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The homeostasis in an organism can be profoundly affected by
endocrine imbalances
Some examples of endocrine disorders: acromegaly goiter, type
I and type II diabetes, rickets, Turner’s syndrome, polycystic
ovary syndrome etc.
In recent years, endocrinologists have focused on the presence
of chemicals in the environment that can potentially disrupt
endocrine functions. These chemicals are called as “Endocrine
Disrupting Compounds (EDCs)”.
EDCs can function directly to disrupt the activities of endocrine
glands or mimics the activities of hormones
Examples of EDCs:
 Insecticides such as DDT or metabolites of DDT
 Herbicides such as atrazine, glyophoste
 Fungicides such as vinclozolin
 Industril or mining byproducts such as heavy metals, dioxins
and PCBs
 Estrogenic or anti-androgenic compounds
 For details, see Table 1-6 in the textbook