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1/13/18

Introduc6on to the course


Endocrinology •  Instructor
11:067:450 •  Course objec5ves
•  Course details
•  References/Text books
Lecture 1 •  Sakai
01/16/2018 •  Exam schedule
•  Grading
•  Syllabus

Course Objec6ves
Instructor: Dr. Aparna Zama
Email: zama@sebs.rutgers.edu •  Develop a thorough understanding of the
mammalian endocrine system
Office: BartleH, Room 209A
•  Cri5cally examine the role of hormones in the
Tel: 848-932-8495 physiology of the organism
Office hours: by appointment, arrange via email •  Study the mechanisms of hormone ac5on
Graduate Teaching Assistant: Mariana Saboya •  Develop an understanding of endocrine
pathologies
Email: mariana.saboya@rutgers.edu

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Course Details Required Textbook

Basic Medical Endocrinology by H. Maurice Goodman


•  Lecture and recitation based
4th Edi5on
•  4 credits, Tuesday, Wednesday, and Friday, all in
Bartlett 123, @ 10:55 AM Academic Press/ Elsevier / ISBN 978-0-12-373975-9

•  Exams and quizzes based on lectures and textbook


Sakai
•  Lectures will be posted in “Resources”
folder in hPps://sakai.rutgers.edu.
•  Lectures highlight the important aspects of
endocrinology as referenced in the
textbook.
•  For success in this course: read relevant
chapter/s, follow lectures carefully, take
detailed notes in class, and revisit
textbook.

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Exams
•  3 exams

•  2 Mid-terms (one hour and 20 minutes each)


Dates: Feb 16 and Mar 27 (during class period)

•  Final exam
Date: Apr 27 (during class period)

•  Mul2ple quizzes are given throughout the


semester
No make-ups for quizzes, under ANY circumstances.

Grading
Two mid-term exams (25% each) 50%
•  Sanc5ons for separable viola5ons include, but are not limited to, one or more of
the following, and may, but need not, involve suspension or expulsion:
•  A grade of XF (disciplinary F) for the course.
One comprehensive final exam 25%
•  Disciplinary proba5on.
•  Dismissal from a departmental or school honors program. Quizzes and assignments 25%
•  Denial of access to internships or research programs.
100%
•  Loss of appointment to academically-based posi5ons.
•  Loss of departmental/graduate program endorsements for internal and external
fellowship support and employment opportuni5es.
•  Removal of fellowship or assistantship support.
•  Suspension for one or more semesters. Fill in the blanks, multiple choices, true/false, short answers, and essays
•  Dismissal from a graduate or professional program.
•  Permanent expulsion from the University with a permanent nota5on of disciplinary
expulsion on the student’s transcript.

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Syllabus
Outline for introductory lectures
•  Hormones and the endocrine system
•  The classifica5on of hormones
•  The biosynthesis, storage, and control
of hormone release
•  Circula5on and metabolism
•  Hormone – receptor interac5ons and
downstream signaling
•  Homeosta5c control
•  Methods used in endocrinology

Hormones
•  Cell-to-cell communica5on molecules
–  Chemical signals, released in small amounts •  Growth factors act at short distances
–  Secreted by a cell or group of cells into the blood – Ac5vates physiological response at low
–  Transported by blood concentra5ons
–  Distant target 5ssue receptors
–  Cellular mechanism of ac5on
•  Ectohormones are released into the environment
•  Depends on binding to target cell receptors •  Pheromones: Elicit physiological or behavioral
•  Ini5ates biochemical responses response on other organisms of the same species
–  Hormone ac5on must be terminated
•  Half-life indicates length of ac5vity

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The Classical/Principal Endocrine Glands


Classic abla6on experiment- Berthold

Organs with Endocrine


Functions
Brain, Heart
Liver, Gastrointestinal tract
Kidneys, Adipose tissue
Testosterone was crystallized in 1935 and shown to be the active substance

Any chemical bioregulation


Endocrine System

•  Levels of organiza5on
•  Structure – Func5on
–  Cell communica5on is cri5cal
•  Homeosta5c regula5on
–  Internal environment has to be maintained
constant within narrow limits, no maHer what
condi5ons prevail in the external environment
–  Feed back mechanisms
The endocrine system, nervous system, and immune system each secretes its own bioregulators: hormones,
neurocrines, and cytocrines, respectively. However, all of these systems influence each other, and from a
homeostatic viewpoint we can assume they function as one great bioregulatory system. 20

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Functional conceptualization of the endocrine system Chemical communica6on between cells

FIGURE 1.1

Kidneys, Gonads, thyroid, Parathyroids,


mammary gland, adrenal cortex, kidneys,
reproductive and and liver heart,
vascular smooth adipose
muscle tissue etc.,

21 22

Chemical communica6on between cells, an Levels at which hormone ac6ons are considered
addi6onal view

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Life history of a hormone


The basic categories of hormones

•  Pep5de or protein hormones


•  Steroid hormones
•  Amino acid–derived or amine hormones

excretion

A hormone is “born” in an endocrine cell and spends its short life “free” in the blood or bound to binding proteins. It may be
metabolized and/or excreted (“die”) before or after it binds to a target cell where it causes changes that result in its characteristic
effect. In some cases, the hormone is secreted in an inactive form and must be metabolized to an active form before it can 25 bind
to its receptor and produce an effect.

Goals and
Objectives

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Comparison of various hormones

Hormone biosynthesis
and release

Know this chart well!

Hormone-secreting cells appear in many formations

Basic molecular
biology of the cell
as related to
hormone
biosynthesis
and release

(A) Cords of 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) A collection of follicles (consisting of an epithelium surrounding a
fluid-filled lumen) from a thyroid gland showing a thin epithelium and pink colloid (a protein suspension) filling the lumen of the 31
follicle. (D) Isolated clusters of testosteronesecreting interstitial cells (arrow) located between seminiferous tubules in a testis.

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Composi6on of DNA Transcription

FIGURE 1.5

FIGURE 1.3

DNA is a polymer of the five-carbon sugar, deoxyribose, in diester linkage with phosphate forming ester
bonds with hydroxyl groups on carbons 3 and 5 on adjacent sugar molecules. The purine and pyrimidine
bases are linked to carbon 1 of each sugar. The numbering system for the five carbons of deoxyribose are
shown at the top of the figure. The chemical bonds forming the backbone of the DNA chain are highlighted
in blue. The 5’ or 3’ ends refer to the carbons in deoxyribose.
33 34

Alternative Splicing
Translation

FIGURE 1.7

FIGURE 1.6

35 36

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Post-transla6onal processing

FIGURE 1.8

The leader sequence or signal pep*de of proteins des5ned for secre5on enters the cisternae of the endoplasmic re5culum
even as pep5de elonga5on con5nues. In the endoplasmic re5culum (1) the leader sequence is removed, (2) the protein is
folded with the assistance of protein chaperons, (3) sulgydryl bridges may form, and (4) carbohydrate may be added
(glycosyla5on). The par5ally processed protein (5) is then entrapped in vesicles that bud off the endoplasmic re5culum and
(6) fuse with the Golgi apparatus, where glycosyla5on is completed, and (7) the protein is packaged for export in secretory
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vesicles in which the final stages of processing take place.

Slide 1

Peptide Hormones - water soluble mRNA


Messenger RNA on the
ribosomes binds amino
acids into a pep6de
chain called a
Preprohormone Ribosome preprohormone. The
chain is directed into
Endoplasmic the ER lumen by a
re6culum (ER) signal sequence of
amino acids.

Signal Prohormone Transport


sequence vesicle Enzymes in the ER
chop off the signal
sequence, crea6ng an
inac6ve prohormone.

The prohormone
passes from the ER
through the Golgi
complex.

Golgi
complex
Secretory vesicles
containing enzymes
and prohormone bud
off the Golgi. The
enzymes chop the
prohormone into one
or more ac6ve
pep6des plus
addi6onal pep6de
Secretory fragments.
vesicle Ac6ve hormone

Cytoplasm Pep6de fragment

Release The secretory vesicle


signal releases its contents
by exocytosis into the
ECF extracellular space.

Plasma The hormone moves


Capillary
To target into the circula6on for
endothelium transport to its target.
© 2016 Pearson Educa5on, Inc.

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Pep6de
Hormone
Synthesis
and
Processing

© 2016 Pearson Educa5on, Inc. © 2016 Pearson Educa5on, Inc.

Release of pep6de hormones

FIGURE 1.9
Exocytosis. 1. Immature secretory vesicles bud off the trans-Golgi stacks. 2. Matura5on of the vesicle
includes extrusion of some proteins and water, acidifica5on of vesicle contents, and condensa5on of
enclosed proteins to form dense core granules. 3. Mature vesicles residing deep in the cytosol as a reserve
pool await a signal for recruitment (4) to the readily releasable pool adjacent to the plasma membrane. 5. In
prepara5on for secre5on, the vesicles become tethered to the membrane (docking). 6. An energy-
dependent interac5on forms a loose associa5on of special proteins (SNARE proteins) in the membranes of
the vesicles with counterparts in the plasma membrane, “priming” the vesicles to respond to a secretory
s5mulus. 7. Secre5on is triggered by an increase in cytoplasmic calcium that produces conforma5onal
changes in the SNARE proteins that brings the membranes of the vesicles into such close apposi5on to the
plasma membrane that fusion occurs and a secretory pore is formed. 8. Expansion of the pore as the vesicle
membrane is incorporated into the plasma membrane releases vesicular contents into the extracellular
fluid.

© 2016 Pearson Educa5on, Inc. 44

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Steroid Hormones- liposoluble


•  Cholesterol-derived
–  Made only in a few organs: adrenal glands and gonads
•  Lipophilic and easily cross membranes
–  Made as needed, not stored
•  Bind carrier proteins in blood
–  Longer half-life
•  Cytoplasmic or nuclear receptors
–  Genomic effect to ac5vate or repress genes for protein
synthesis
–  Slower ac5ng
•  Cell membrane receptors
–  Nongenomic responses

Steroid hormone synthesis

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Hormones: Amino Acid–Derived, Tyrosine

Amine
is the parent amino acid for
catecholamines and thyroid hormones.

or Amine
hormones
•  Amine hormones: Tryptophan - melatonin Catecholamines Thyroid hormones
are synthesized from two
are made by modifying

•  Amine hormones: Tyrosine


the side groups of tyrosine. tyrosines and iodine (I) atoms.

–  Catecholamines Not discussing


this now
–  Epinephrine Dopamine

Thyroxine (Tetraiodothyronine, T4)


–  Norepinephrine
–  Dopamine Norepinephrine

•  Thyroid hormones
Epinephrine Triiodothyronine (T3)

Hormones in the blood circulation


Specificity of hormone signaling

Blood

Cell Cell
Endocrine without with
cell receptor receptor Target
cell

No response

FIGURE 1.10
Response

Hormone binding to plasma proteins. Bound hormone is in equilibrium with a small frac5on of “free” unbound hormone.
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Only the free hormone can pass through capillary endothelium to reach target cells or sites of degrada5on.

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Specificity of hormone signaling

FIGURE 1.11

Although all cells come in contact with the hormone, only the cells colored blue have receptors and therefore can respond
to the hormone. (H = hormone; HR = hormone receptor) 53

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