Endocrinology

1
Endocrinology First test on Sept 15 Typo on
Syllabus Exam 3 on NOV 10 PHOTOS for those
absent on MONDAY or will be dropped from class

on-line http//www.biology.lsu.edu/webfac/jsteph
ens/courses.html
2
HUMORAL Of, relating to, proceeding from or
involving a bodily humor now often used of
endocrine factors as opposed to neural or
somatic. humoral 1 of, relating to,
proceeding from, or involving a bodily humor (as
a hormone) lthumoral control of sugar metabolismgt
HUMORAL adj of or relating to bodily
fluids HUMORAL (FLUID), SOMATIC (BODY) OR NEURAL


3
Homeostasis resistance to change involves the
maintenance of blood concentrations of numerous
molecules and ions that are essential to life and
the maintenance at specified levels of other
physical parameters such as temperature.

4
Endocrine Glands and their hormones Tissues-comp
osed of one (or several cell types) Often have a
number of tissues in an organ Each Tissue type
has connective tissue blood vessels nerves.


5
Endocrine glands (ductless glands that secrete
products directly into the bloodstream Exocrine
glands release their products into ducts
leading to lumen of other organs

6
Often just one cell type in a tissue that makes
the hormone Adrenal glands Pancreas- GI
hormones and many other examples
7
Transient endocrine gland

8
If you secrete one, you likely secrete many
Endocrine glands usually secrete more than one
hormone Examples EXCEPTION-parathyroid

9
Other experiments 1902-Bayliss and Starling
-Substance liberated by mucosa of SI stimulates
flow of pancreatic juice Pancreatic enzyme
secretion mediated by humoral rather than nervous
stimulation Secretin- First hormone identified

10
Other experiments 1889- Von Merling and
Minikowski removal of dog pancreas led to
diabetes mellitus.

11
Other experiments Banting and Best found
that islets of langerhans (rather than pancreatic
acinar cells) were needed for control of
carbohydrate metabolism 1922-extracts from
pancreatic islet cells caused decreases in blood
glucose in diabetic dogs. http//www.discoveryo
finsulin.com/Introduction.htm

12
No longer separate nervous system and endocrine
system. Hormones derived from nerve cells called
neurohormones or neuropeptides Neurotransmitters-
chemical messenger released from synapse between
nerve and effector cell Neuromodulators-slower
acting

13

14
Peptides and proteins Steroids Amino acid
derivatives Fatty acid derivates-Eicosanoids
15
hormones are synthesized, exist in a
biologically active state for a time, and then
degrade or are destroyed. Having an
appreciation for the "half-life" and mode of
elimination of a hormone aids in understanding
its role in physiology and is critical when using
hormones as drugs.
16
Comparison to get you thinking Structure
KNOWLEGDE Peptides and proteins- Hydrophillic Sho
rter half lives cell surface receptors Steroids H
ydrophobic Longer half lives Intracellular
receptors
17
Peptides and Proteins Peptide and protein
hormones are, of course, products of translation.
vary in size and post-translational
modifications
18
Peptide Hormones -made of AAs 3 to gt180aa Variety
of structures Linear, multiple chains,
ringed Some of the larger protein hormones are
glycoproteins-FSH, LSH, TSH, hCG AA sequence of
a hormone may differ between species Can have
different roles in different species

19

20
Peptide hormones are made via the secretory
pathway. They can be secreted by one of two
pathways Regulated secretion Constitutive
secretion
21

22
They can be secreted by one of two pathways
Regulated secretion The cell stores hormone in
secretory granules and releases them in "bursts"
when stimulated. This is the most commonly used
pathway and allows cells to secrete a large
amount of hormone over a short period of time.
Constitutive secretion The cell does not store
hormone, but secretes it from secretory vesicles
as it is synthesized.
23
Peptide growth stimulating factors Variety of
peptides have growth promoting activities NGF FGF
EGF EPO In general, the half-life of circulating
peptide hormones is only a few minutes.

24
IMPORTANT NOTE ON Thyroid Hormones Made from
amino acids (so like a peptide hormone), but does
not have a cell surface receptor (like most
peptide hormones) Has INTRACELLULAR
RECEPTOR Classified as AA derivative

25

Steroids Steroids are lipids and, more
specifically, derivatives of cholesterol.
Examples include the sex steroids and adrenal
steroids The first and rate-limiting step in
the synthesis of all steriod hormones is
conversion of cholesterol to pregnenolone.
26
Steroid Hormones Tissue of gonads produce sex
steroids Androgens Estrogens- Progestins-


27
Steroid Hormones Sex steroids important in
development Structure -

28
Steroid Hormones Produced by Steriodogenic
tissue of adrenal or gonads Adrenal glands

29

• Steroid hormones are derivatives of cholesterol
  that are synthesized by a variety of tissues,
  most prominently the adrenals and gonads.
• The cholesterol precursor comes from cholesterol
• -synthesized within the cell from acetate, from
  cholesterol ester stores in intracellular lipid
  droplets or
• -from uptake of cholesterol-containing low
  density lipoproteins (LDL). Lipoproteins taken up
  from plasma are most important when steroidogenic
  cells are chronically stimulated.

30

Steroids- lipids cholesterol derivatives sex
steroids and adrenal steroids. The first and
rate-limiting step in the synthesis of all
steriod hormones is conversion of cholesterol to
pregnenolone. Pregnenolone is formed on the inner
membrane of mitochondria then shuttled back and
forth between mitochondrion and the endoplasmic
reticulum for further enzymatic transformations
involved in synthesis of derivative steroid
hormones.
31

• Biosynthesis of steroid hormones requires a
  battery of oxidative enzymes
• A rate-limiting step in this process is the
  transport of free cholesterol from the cytoplasm
  into mitochondria.
• Within mitochondria, cholesterol is converted to
  pregnenolone by an enzyme in the inner membrane
  called CYP11A1. Pregnenolone itself is not a
  hormone

32

• 5 groups of steroid hormones
• Glucocorticoids
• Mineralocorticoids
• Androgens
• Estrogens,
• Progestogens

33

• Steroids DO NOT BIND TO CELL SURFACE RECEPTORS
• The biosynthetic pathways for major
  representatives of these classes of steroid
  hormones is depicted in the following diagram. Be
  aware that a variety of related molecules exist,
  some of which may have significant effects,
  particularly in certain pathologic conditions.

34
(No Transcript)
35

Newly synthesized steroid hormones are rapidly
secreted from the cell, with little if any
storage. Increases in secretion reflect
accelerated rates of synthesis. Following
secretion, all steroids bind to some extent to
plasma proteins. This binding is often low
affinity and non-specific (e.g. to albumin), but
some steroids are transported by specific binding
proteins, which clearly affects their halflife
and rate of elimination. Steroid hormones are
typically eliminated by inactivating metabolic
transformations and excretion in urine or bile.
36
Amino Acid Derivatives There are 2 groups of
hormones derived from the amino acid tyrosine
Thyroid hormones Catecholamines
37
Thyroid Hormones Thyroid gland makes two
hormones Thyroxine T4 and Triodothyrosine T3
Two hormones have diverse functions in
vertebrates Unique property-inorganic ion in
their structures

38
The pathways of synthesis of these hormones will
be covered in lectures on thyroid gland and
adrenal medulla. The circulating half-life of
thyroid hormones is on the order of a few days.
They are inactivated primarily by intracellular
deiodinases. Catecholamines, on the other hand,
are rapidly degraded, with circulating half-lives
of only a few minutes.
39
Two other amino acids are used for synthesis
of hormones Tryptophan is the precursor to
serotonin and the pineal hormone melatonin
Glutamic acid is converted to histamine
40
Fatty Acid Derivatives - Eicosanoids
Eicosanoids derived from polyunsaturated fatty
acids. The principal groups of hormones of this
class are prostaglandins Prostacyclins leukotriene
s and thromboxanes.
41
Fatty Acid Derivatives - Eicosanoids
Prostaglandins Prostacyclins leukotrienes and
thromboxanes.
42
Fatty Acid Derivatives - Eicosanoids Stores of
arachadonic acid (AA) are present in membrane
lipids and released. The specific eicosanoids
synthesized by a cell are dictated by the battery
of processing enzymes expressed in that cell.
typically active for only a few seconds.
43
Eicosanoids Prostaglandins Discovered fairly
recently PGA to PGJ designation
44
Neurotransmitters Neurohormones made by neurons
and usually release in specializes structures
(synaptic cleft) near the target
cells Neurotransmitter-regulate another nerve
cell or a muscle cell or secretory cell or other
cell type COMMON NTs Acetylcholine, NE, dopamine,
serotonin

45
Dopamine- a NT Released from hypothalamic
neurons but also functions as hormone in blood.
Can act to regulation secretion of hormones from
Pituitary

46
Neuropeptides Many peptide hormone found in
brain where are made in specific neurons. Work
primarily in nervous system???? Some
distributed throughout the CNS ENDORPHINS-functio
n as neuroregulators that act on opiate receptors
and in humans can act as analgesic hormones.

47
Most hormones act on animal in which they are
produced. Pheromones

48
Pheromones May work between species?? Important
roles in insects and other invertebrates Generally
aliphatic-facilitate their volatilization and
subsequent transport in the air

49
Pheromones Chemically pure pheromone, they
named it "bombykol" for the silkworm moth,
"Bombyx mori" from which it was extracted. It
signaled, "come to me!" from great distances.