Wingfield 3

Wingfield 3 - NPB
101,
Autumn
2008
 Endocrinology...

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Unformatted text preview: NPB
101,
Autumn
2008
 Endocrinology 3. Endocrine Glands That are Not Primary Targets of the Anterior Pituitary Calcium Regulating Hormones Five
major
types
of
endocrine
secre=ons
not

 under
direct
control
of
the
pituitary
gland
 Hormones
of
the
immune
system.
E.g.
monokines
and
lymphokines

 Osmoregulatory
hormones
such
as
aldosterone
(Renin‐angiotensin

 system),
atrial
natriure=c
factor
 Neural
hormones
from
the
pineal
(melatonin)
and
adrenal

 medulla
(catecholamines)
 Calcium
regula=ng
hormones
such
as
parathormone,
calcitonin

 and
vitamin
D
 Hormones
of
the
gastrointes=nal
tract
and
pancreas
(e.g.
gastrin,

 secre=n,
cholecystokinin,
insulin
and
glucagon)
 Some
are
regulated
primarily
by
the
autonomic
nervous
system

 
(e.g.
the
adrenal
medulla)
 Others
respond
directly
to
circula=ng
metabolites
such
as
calcium

 
(parathormone,
calcitonin,
vitamin
D)
 Circula=ng
glucose
(pancrea=c
hormones),
also
faNy
acids
and
 
amino
acids

 To
compounds
in
the
gastro‐intes=nal
tract
(the
G.I.
tract

 
hormones
gastrin,
secre=n
and
cholecystokinin)‐
direct
 
environmental
effects
 Some
hormones
from
the
anterior
pituitary
may
influence
ac=vity

 
of
these
peripheral
endocrine
=ssues
but
these
effects
tend
to
be

 
"fine‐tuning"
regula=on
and
not
the
primary
control
mechanisms
 Calcium
regula=on
and
the
hormones
that
control
it
 Low
blood
calcium
results
in
uncontrolled
muscle
contrac=ons

 
(hyper
excitability
of
membranes);
decreased
ac=va=on
of
cell

 
enzymes;
inhibi=on
of
blood
clo[ng
and
reduced
cell
adhesion
 Phosphates
act
as
buffers;
are
important
in
synthesis
of
nucleic

 
acids,
phosphoproteins,
phospholipids
and
the
phosphoryla=on

 
of
proteins
 Addi=onally,
both
calcium
and
phosphate
are
major
components

 
of
bone
and
teeth
 Calcium
and
phosphate
mobiliza=on,
deposi=on
and
storage,
and
 
absorp=on
from
the
gut
are
regulated
by
three
major
hormones:

 
parathormone,
calcitonin
and
vitamin
D
 Osteocyte
 Central
 canal
 Lamella
 Canaliculi
 Osteon
 Blood
vessel
 from
marrow
 Central
 canal
 Vessel
in
central
canal
 Stepped
art
 Fig.
19‐20,
p.
719
 Osteoblast
 Osteocyte
 Osteocy=c–
 osteoblas=c
bone
 membrane
 Osteoblast
 Outer
 surface
 Mineralized
 bone
 Blood
vessel
 Canaliculi
 Lamellae
 Bone
fluid
 Central
canal
 Fig.
19‐21a,
p.
722
 Compact
Bone.
This
image
shows
osteocytes
within
their
lacunae.

 Note
the
basophilic
cytoplasm
of
the
osteocytes
and
the
dark
staining

 nuclei.
See
also
the
delicate
canaliculi
that
radiate
from
each
lacuna.
 Compact
Bone.
In
the
upper
central
por=on
of
the
image
is
a
cross

 sec=on
of
a
Haversian
System,
including
the
Haversian
canal,

 osteocytes
within
lacunae
and
the
concentric
lamellae.
Note
again
the

 presence
of
numerous
canaliculi
radia=ng
from
the
lacunae.
 Compact
Bone.
The
pointer
indicates
a
Haversian
canal
with
 erythrocytes
and
a
thin
lining
endothelium.
Note
concentric
lamellae

 of
the
Haversian
system
and
osteocytes
within
their
lacunae.
 Cancellous
Bone.
In
this
photomicrograph,
note
a
trabeculus
or
beam
of

 cancellous
bone
running
from
lower
leb
to
upper
central.
Flanking
the
trabeculae

 are
marrow
cavi=es.
These
form
the
red
bone
marrow,
ac=ve
in
the
forma=on
of

 blood
cells
(hemopoiesis).
In
the
trabeculus,
there
are
osteocytes
residing
within

 lacunae,
and
the
irregular
cement
lines
that
separate
the
layers
of
lamellae
of

 bone.
Along
the
periphery
of
the
trabeculus
are
bone
forming
cells
known
as

 osteoblasts.
 Resorbing
Bone.
In
the
normal
course
of
events,
bone
is
resorbed
as

 well
as
deposited.
Such
bone
resorp=on
is
associated
with
a
cell

 known
as
an
osteoclast
(indicated
the
pointer).
 At
increased
magnifica=on,
the
osteoclast
is
seen
as
a
very
large

 mul=‐nucleated
cell.
 Fig.
19‐21b,
p.
722
 Fig.
19‐22,
p.
723
 Colloid
 Parafollicular
cells
 Follicle
cells
 Tangen=al
sec=on
through
por=ons
of
two
thyroid
follicles.
The
cells

 in
the
lower
right
are
parafollicular
or
C‐cells,
and
contain
numerous

 small
granules.
A
capillary
is
present
between
follicles.

 Capillaries
 Oxyphil
cells
 Chief
cells
 Parathyroid
of
mammal
at
higher
magnifica=on:

 Chief
cells,
oxyphil
cells
and
capillaries

 Fig.
6
 Capillary
 Chief
cell
 Low
magnifica=on
electron
micrograph
of
parathyroid
gland
showing
chief
cells,

 an
oxyphil
cell
(OX)
and
a
capillary.
Chief
cells
are
the
major
cell
type
and
contain

 modest
amounts
of
granular
ER,
some
lipid
droplets,
small
amounts
of
glycogen,

 and
secre=on
granules.
Oxyphil
cell
are
characterized
by
numerous
mitochondria.

 Parathormone
 A
polypep=de
of
84
amino
acids
from
a
precursor
molecule
of

 
about
115
amino
acids
in
chief
cells
 In
mammals,
PTH
is
cleaved
in
the
blood
circula=on
to
give

 
pep=des
of
varying
length
 The
amino
acid
sequence
1‐34
is
essen=al
for
biological
ac=vity
 Ac=ons
of
Parathormone
and
control
of
secre=on
 Removal
of
the
parathyroid
gland
results
in
rapid
death
and
muscle

 
tetany
 Injec=on
of
parathyroid
extracts
maintains
life
 PTH
injec=ons
increase
blood
levels
of
Ca2+
both
directly
and

 
indirectly
 Release
of
PTH
is
controlled
by
circula=ng
Ca2+

 Therefore
there
must
be
recogni=on
sites
for
calcium
ion
on

 
parathyroid
gland
cells
because
the
parathyroid
gland
can
respond

 
with
increased
PTH
secre=on
to
low
Ca2+
concentra=on
in
vitro
 Low
levels
of
Ca2+
result
in
increased
PTH
secre=on
 High
levels
decrease
PTH
release
 Incuba=on
of
parathyroid
gland
cells
with
c‐AMP
also
releases

 
PTH
sugges=ng
that
the
calcium
recogni=on
site
acts
through

 
c‐AMP
as
a
second
cell
messenger
 Bone.

Complex
ac=ons
of
PTH
here.
It
can:

 Parathormone
affects
calcium
transport
at
three

 targets:
bone,
kidney
and
gut
 a).
increase
c‐AMP
levels
in
bone
 b).
elevate
conversion
of
connec=ve
=ssue
into
osteoclasts
(that

 




control
bone
resorb=on)
 c).
s=mulate
bone‐turnover
(independently
of
c‐AMP)
 d).
ac=vates
exis=ng
osteoclasts
(no
c‐AMP)
 e).
increase
metabolism
of
bone
cells
including
osteoclasts
(i.e.

 




elevates
organic
acids
and
enzymes
involved
in
bone
resorb=on,

 




collagenase,
hyaluronic
acid)
 f).
increases
osteocytes
(regulate
bone
deposi=on
and
also
resorb=on)

 




to
transport
Ca2+
to
bone
fluid
and
on
intoextra‐cellular
fluid
 




(c‐AMP
dependent)
 g).
increase
permeability
of
osteoblast
(regulates
collagen
synthesis

 




and
provides
a
template
for
hydroxyapa=te
and
bone
building)
 




membranes
to
Ca2+
and
influx
into
the
cell.

 Parathormone
affects
calcium
transport
at
three

 targets:
bone,
kidney
and
gut
 Kidney.

PTH
can
elevate
Ca2+
re
absorp=on
and
phosphate

 
excre=on
resul=ng
in
moderate
water
diuresis.

 This
requires
c‐AMP
in
renal
tubular
cells
and
may
act
as
a

 
mechanism
to
get
rid
of
phosphate
ions
from
bone
resorb=on
but

 
retain
the
calcium
 Calcium
re‐absorp=on
occurs
in
the
distal
tubule
only
 Intes=ne.
PTH
increases
ca2+
absorp=on
from
the
gut,
but
high

 
doses
are
needed
 Vitamin
D
is
essen=al
for
ac=ons
of
PTH
on
the
gut
 PTH
also
s=mulates
vitamin
D
secre=on
which
in
turn
poten=ates

 
calcium
absorp=on
 Calcitonin
 Calcitonin
is
a
pep=de
of
32
amino
acids
with
a
fairly
high
degree
of

 
homology
from
humans
to
salmon
 The
prohormone
is
much
larger
(up
to
100
amino
acids)
 Calcitonin
tends
to
decrease
blood
calcium
and
phosphate
levels

 
(i.e.
the
opposite
of
PTH)
 The
gene
for
calcitonin
also
codes
for
calcitonin‐gene‐related

 
pep=de
(CRGP)
that
is
ac=ve
in
neural
=ssue
 It
can
increase
arterial
blood
pressure
and
heart
rate
when
injected

 
into
ventricles
of
the
brain
 It
decreases
arterial
blood
pressure
when
injected
intra‐venously
 A
‐
cells
of
the
developing
thyroid
stained

 with
an
an=body
against
calcitonin.
 Calcitonin
‐
control
of
secre=on
and
ac=ons
 High
extracellular
Ca2+
concentra=ons
increase
circula=ng

 
calcitonin
levels
(c‐AMP
is
also
involved
in
ul=mobranchial
cells)
 GI
tract
hormones
(gastrin
and
cholecystokinin)
increase
calcitonin

 
release
possibly
in
an=cipa=on
of
elevated
dietary
calcium

 
absorp=on
 Calcitonin
secre=on
results
in:
 a).
A
decrease
in
blood
levels
of
Ca
ions
and
phosphate,
 but
this
is
a
fine
tuning
effect
(no
dras=c
loss
of
calcium)
 b).
Increases
in
urinary
excre=on
of
calcium
and
phosphate
 ions,
sodium,
potassium
and
magnesium
ions
accompanied
 by
elevated
diuresis
 c).
Increases
in
bone
Ca2+
deposi=on
and
decreases
effects

 of
PTH.
 No
clear
cut
effects
on
G.I.
tract
and
calcium
absorp=on
 Calcitonin
‐
mechanisms
of
ac=on
 Binds
to
membrane
receptors
in
kidney
and
bone,
but
does
not

 
decrease
PTH
ac=vity
because
effects
persist
in

 
parathyroidectomized
animals
 Calcitonin‐receptor
complex
ac=vates
adenylate
cyclase
through

 
a
G
protein
resul=ng
in
an
increase
in
cAMP
levels
 There
follows
a
decrease
in
Ca2+
concentra=ons
in
the
cytoplasm
 
and
phosphoryla=on
of
kinase
cascades
 Vitamin
D
 Essen=al
for
the
absorp=on
of
Ca2+
from
the
gut
and
for
bone

 
Ca2+
mobiliza=on
 Vitamin
D
is
a
steroid
prohormone
(vitamin
D3,
or
cholecalciferol)

 
that
is
converted
to
1,25
dihydroxycholecalciferol
(the
ac=ve
form)
 It
is
synthesized
in
the
skin
from
7‐dehydroxycholesterol
under

 
U.V.
light
to
give
previtamin
D3
 Thermal
isomeriza=on
then
gives
vitamin
D3
(cholecalciferol)
 Vitamin
D3
is
also
ingested
in
the
diet
‐
especially
fish
and
meat.

 
It
is
also
provided
as
a
supplement
in
several
foods
 Vitamin
D3
is
transported
bound
to
a
binding
protein
in
blood
to
the

 
liver
and
kidney
where
it
is
hydroxylated
to
1,25

 
dihydroxycholecalciferol
 This
hydroxyla=on
is
s=mulated
by
low
concentra=ons
of

 
phosphate
ions,
PTH
or
estradiol
 Vitamin
D
nuclear
 receptor
 Calciferol
 (Cholecaliferol)
 Biological
roles
of
Vitamin
D

 (Calciferol,
Cholecalciferol)
 Vitamin
D
acts
at
the
levels
of
intes=ne,
bone
and
kidney

 1.  Intes=ne.

Increases
calcium
and
phosphate
ions
transport

 across
the
gut
wall
against
a
concentra=on
gradient.
There
is
ac=ve

 transport
across
mucosal
cells,
mostly
in
the
duodenum.
This

 ac=on
does
not
require
PTH.
 2.
Bone.

Vitamin
D
deficiency
results
in
"Rickets"
(osteomalacia)

 in
which
the
bones
become
under‐mineralized.
Plasma
calcium

 levels
are
low.
Injec=ons
of
Vitamin
D
increase
bone

 mineraliza=on
and
increase
plasma
calcium.
The
major
effect
is

 on
bone
calcium
mobiliza=on
and
bone
remodeling.
 3.
Kidney.

May
increase
renal
reabsorp=on
of
calcium
by
renal

 tubules.
However,
this
effect
is
not
always
replicable.

 Rickets
 Dietary
supplementa=on
of
Vitamin
D

 has
gone
a
long
way
toward
abolishing
 dietary
rickets,
but
it
s=ll
is
occasionally
 seen
in
less
developed
countries
and
in
 circumstances
of
dietary
problems.
 Hereditary
forms
of
rickets
are
also
seen.
 Rickets
causes
a
dis=nc=ve
cupping
and
 widening
of
the
growth
plates
which
can
 be
recognized
on
a
plain
x‐ray
along
with
 other
characteris=cs.
Treatment
of
the

 underlying
rickets
leads
to
correc=on

 of
bowing.
 A
child
with
rickets,
knee

 demonstra=ng
classic

 metaphyseal
fraying
and

 physeal
widening.
 www.nlm.nih.gov/.../ency/imagepages/17156.htm
 The
bone
disease
osteoporosis
is
caused
by
more
bone
cells
being
resorbed
than
 
being
deposited.
Lack
of
estrogen,
hyperparathyroidism
and
Vitamin
D
deficiency
 can
contribute.
 ...
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