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The endocrine system
Major Endocrine Glands
15.1 Endocrine glands
What is a target cell?
Circulating and local hormones
•
•
•
Circulating
hormones enter the
blood.
Paracrine hormones
act on neighboring
cells.
Autocrine hormones
act on the
secreting cell.
Hormones
Receptors
Long Distance Communication:
Endocrine Hormones
•
•
•
•
Signal Chemicals
Made in
endocrine cells
Transported via
blood
Receptors on
target cells
Figure 6-2a: Long distance cell-to-cell communication
Paracrine and Autocrine Hormones
•
•
•
Local communication
Signal chemicals
diffuse to target
Example: Cytokines
» Autocrine–receptor
on
same cell
» Paracrine–neighboring
cells
Figure 6-1c: Direct and local cell-to-cell communication
Mechanisms of Hormone Action
•
Endocrine
– hormones
•
Paracrine
– hormones
•
Autocrine
secreted into the blood
acting on downstream target
tissues.
secreted into the interstitial
space acting at nearby cells.
– hormones
secreted into the interstitial
space acting back on same cell.
Figure 6-2b, c: Long distance cell-to-cell communication
Comparison of Nervous System and
Endocrine System
• Neurons release
neurotransmitters into
a synapse, affecting
postsynaptic cells
• Glands release
hormones into the
bloodstream
• Only target cells of
hormone responds
Hormones are Extremely Powerful
ACAT: acyl CoA;cholesterol acyl transferase;
ACTH: adrenocorticotropic hormone
AT: angiotensin II; LH: luteinizing hormone
Acetyl CoA
biosynthesis
LDL
Cholesterol
from plasma
outer
membrane
Cholesterol
Cholesterol
esters
ACAT
inhibited by: AT, ACTH , LH
 AT (ZG)
 ACTH (ZF)
 LH (gonads)
StAR
storage
vacuole
Fatty acids
cholesterol esterase: activated by
AT in ZG (IP3-DAG)
ACTH in ZF (cAMP)
LH in gonads (cAMP)
Cholesterol
Steroidogenic acute
regulatory protein
Pregnenolone SER
MITOCHONDRION
matrix
inner
membrane
P-450scc: ACTH-activated: ZF
AT-activated: ZG
LH-activated: gonads
Figure 2. Initial events common to the biosynthesis of steroid hormones
Ca2+
Microfilaments
........
.
7
6
Secretory
granules
5
Microtubules
4
Golgi
Glucose
Transfer
uptake
vesicles
Figure 5.
Structural
components
Endoplasmic
reticulum
(italicized) of the
pancreatic -cell
involved in
glucose-induced
biosynthesis and Biological structures
Nucleus
release of insulin.
Granule fusion
with membrane;
Exocytosis of insulin
Ca2+ contraction
Of microfilaments
Insulin storage
Proinsulin to insulin;
Packaging of insulin
Transport of
proinsulin to Golgi
3
2
1
Synthesis of preproinsul
Uptake into ER;
Excision of signal peptid
Disulfide bonds formed
mRNA production;
Preproinsulin gene
transcription
Mechanism of Hormone Action
Protein Hormones
(cAMP second messenger)
LH
Receptor
G
Plasma Membrane
Adenylate Cyclase
R
C
S-ER
Protein Kinase A
(PKA)
Steroid Synthesis
Mitochondria
Nucleus
Protein
Synthesis
(Enzymes)
Synthesis
R-ER
Protein
DNA
Mechanism of Hormone Action
Protein Hormones
(cAMP second messenger)
LH
G
Receptor
Plasma Membrane
Adenylate Cyclase
ATP
cAMP
S-ER
cAMP
R
C
Protein Kinase A
(PKA)
Steroid Synthesis
Mitochondria
Nucleus
Protein
Synthesis
(Enzymes)
Synthesis
R-ER
Protein
DNA
Mechanism of Hormone Action
Protein Hormones
(cAMP second messenger)
LH
G
Receptor
Plasma Membrane
Adenylate Cyclase
cAMP
ATP
R
cAMP
Protein Kinase A
(PKA)
S-ER
Steroid Synthesis
C
(+ PO4)
Mitochondria
Histones
Nucleus
Protein
Synthesis
(Enzymes)
Synthesis
R-ER
Protein
mRNA
DNA
Mechanism of Hormone Action
Protein Hormones
(cAMP second messenger)
LH
G
Receptor
Plasma Membrane
Adenylate Cyclase
cAMP
Testosterone
ATP
R
cAMP
Protein Kinase A
(PKA)
S-ER
Steroid Synthesis
C
(+ PO4)
Mitochondria
Cholesterol
Pregnenolone
Histones
Cholesterol
Protein
Synthesis
(Enzymes)
Synthesis
R-ER
Protein
mRNA
Nucleus
DNA
Nonsteroid Hormone Action
Figure 9.1b
Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings
Slide 9.9
Steroid Hormone Action
Figure 9.1a
Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings
Slide 9.7
Action of a steroid hormone
HYPOTHALAMUS
Master control
Master integrator
hypothalamus
infundibulum
PITUITARY GLAND
AKA = hypophysis
Infundibulum
Sella turcica
pituitary gland
sella turcica in
sphenoid bone
Location of the Pituitary
Sella turcica of the sphlenoid bone
Hypothalamic releasing & inhibiting hormones
•
•
•
•
Thyrotropin releasing hormone (TRH)
Corticotropin releasing hormone (CRH)
Growth hormone releasing hormone (GHRH)
Growth hormone inhibitory hormone (GHIH)
(Somatostatin)
•
•
Gonadotropin releasing hormone (GnRH)
Prolactin inhibitory hormone (PIH)
» Prolactin
releasing hormone (PRH)
Hypothalamic Hormones
Hypothalamic Hormones:
Gondotropin RF
Corticotropin RF
Thyrotropin RF
Growth Hor RF
Prolactin RF
(CRF)
Pituitary Hormones:
Follicle SH &
Lutenizing Hor.
Adrenocorticoptropin Thyrotropin SH Growth
Hormone
Hormone (ACTH)
Prolactin
Target Gland or Structure:
Ovaries & Testes
(androgens, estrogen)
Adrenal Gland
Thyroid Gland
(cortisol)
(thyroxine)
Cells of body
Bones, breasts
& cells of body
Endocrine Feedback Loops
•
•
Negative
» gonadal steriods
– Testosterone, Progesterone, Estradiol
» Protein hormones
– inhibin
Positive
» Gonadal
steroids
– estradiol
Control of Hormonal Secretions
• primarily controlled by negative feedback mechanism
Positive/Negative Feedback loop
Neural input
Hypothalamus
Inhibiting
factors
+
Releasing factors
Pituitary gland
+
Hormone A
Target organ
+
Hormone B
Important Point: Secretions are pulsatile vs. continuous
Thyrotrophs (5%)
Neural input
Hypothalamus
+
Thyrotropin RH via
dorsomedial nucleus
Pituitary gland
+
TSH
Thyroid Gland
+
T3(inhibitory)
T4
Defects? Hypothyroidism
- At the level of the pituitary gland results in low levels of TSH and T3/T4
- At the level of the thyroid gland results in normal levels of TSH and low levels of
T3/T4
Hypothalamus
TRH
Somatostatin
Anterior
Pituitary
Estrogen
Feedback
inhibition on
hypothalamus
TRH secretion
Thyrotropin (TSH)
Growth
hormone (GH)
Glucocorticoids
Thyroid gland
Thyroid hormones (T4 and T3)
Feedback
inhibition on
pituitary TSH
secretion
Complex negative feedback
Controlling centers of the CNS
Neural pathways
Hypothalamus
Hypothalamic hormones
Adenohypophysis
Adenohypophysal hormones
Peripheral glands
Hormones of peripheral glands
Tissue
Negative Feedback Regulation of
Spermatogenesis
•
•
both testosterone and
inhibin feed back to
hypothalamus and
pituitary to inhibit FSH
and LH secretion
sperm production
maintained at a relatively
constant level (note:
testosterone also needed
for sperm production)
Pituitary gland
•
Be able to
identify which
hormone comes
from the
anterior and
posterior
pituitary
• Hormones:
FSH, LH,
ACTH, TSH,
GH, PRL, MSH,
OT, ADH
Pituitary gland – (the hyperlinks work on this page)
PARS DISTALIS: chromophils (50%) and
chromophobes (50%). The chromophils can be
further subdivided into acidophils (40%) and
basophils (10%). The acidophils secrete GH
(somatotropes) and prolactin (mammotropes).
Basophils secrete TSH (thyrotropes), LH
(gonadotropes), FSH (gonadotropes), and
ACTH (corticotropes).
PARS NERVOSA: main cell type here is a glial
or supporting cell called a pituicyte . The bulk
of the pars nervosa consists of axons from
neurons in the supraoptic and paraventricular
nuclei of the hypothalamus.
PARS INTERMEDIA: rudimentary in humans,
lies between the pars distalis and pars
nervosa.
BE ABLE TO IDENTIFY THE STRUCTURES
WITH HYPERLINKS
Hormones of the Anterior Pituitary
Figure 9.4
Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings
Slide 9.17
Anterior pituitary
Regulation
Hormone
Target organ
Action
Pathology
GHRH and GHIH
Growth hormone (GH)
Many cells (bones..)
Stimulate cell
growth and cell
division
- not enough:
children  pituitary
dwarfism
too much: gigantism
(children) –
acromegaly (adult)
PRH - PIH
Prolactin (PL)
Breast secretory
cells
- milk secretion
--
TRH
Thyroid stimulating
hormone (TSH)
Thyroid gland
- promote
thyroid gland
secretion (T3
and T4)
- not enough:
hypothyroidism
(cretinism in
children)
- too much:
hyperthyroidism
CRH
Adrenocorticotropic
hormone (ACTH)
Adrenal cortex (3
layers)
- stimulates
secretion of
adrenal cortex
- not enough:
Addison's disease
- too much: Cushing
syndrome
GnRH
Gonadotropin
- Follicle stimulating
hormone (FSH)
- Luteinizing hormone
(LH)
Stimulate gamete
maturation
Stimulate
gonadal gland
secretion and
gamete
formation
- infertility
Figure 6.8
Higher centers
Stress
Suckling stimulus
Dopamine
Ant Pituitary
PRL
Breast
Milk production
PRL
Afferent Stimulatory pathway
I
I
TRH
+
Control of Prolactin
+
+
+
Hypothalamus
Stress
+
Ant Pituitary
ACTH
+
Adrenal Gland
Cortisol
ACTH
I
Cortisol
+
CRH
I
Control of ACTH
I
I
Hypothalamus
Higher centres
I
+
Dopamine
Somatostatin
I
Ant Pituitary
TSH
+
Thyroid Gland
T3 + T4
TSH
TRH
I
Control of TSH
I
I
Hypothalamus
+
GnRH
I
I
Ant Pituitary
LH
FSH
+
+
Control of LH & FSH
In Male
I
I
Hypothalamus
Testes
Leydig Cells Sertoli cells
+
Testosterone
Inhibin
+
GnRH
I
I+
Ant Pituitary
LH
FSH
+
+
Control of LH & FSH
In Female
I
I+
Hypothalamus
Ovary
Oestradiol
Progesterone
Inhibin
Pituitary & Hypothalamus
Hormones of the Posterior Pituitary
Figure 9.5
Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings
Slide 9.22b
Stretch receptors
Stretch receptors
Hypothalamus
Post Pituitary
Oxytocin
Mammary gland
+
+
Control of Oxytocin
Higher Centers
Uterus
Higher Centers
Hypothalamus
Osmoreceptors
Post Pituitary
H2O
Vasopressin
Kidney
Blood Vessel
Stretch receptors
Control of Vasopressin
Baroreceptors
ANTI-DIURETIC HORMONE
AKA = vasopressin
Hypothalamic osmoreceptors
Water reabsorption
dehydration
increased interstitial fluid osmotic pressure
stimulation of hypothalamic osmoreceptors
( -)
secretion of ADH from posterior pituitary gland
1. WATER REABSORPTION BY KIDNEYS
2. decreased perspiration
increased water in blood
increased interstitial fluid osmotic pressure
Hormones of Adenohypophysis
•
Somatotropes – human growth hormone (hGH)
•
Corticotropes – adrenocorticotropin (ACTH)
» Melanocyte stimulating hormone (MSH)
•
Thyrotropes – Thyroid stimulating hormone (TSH)
•
Gonadotropes – gonadotropic hormones
» Luteinizing hormone (LH)
» Follicle stimulating hormone (FSH)
•
Lactotropes – prolactin (PRL)
Hormonal Stimuli
Figure 16.5c
Figure 58-1 Hormones and releasing factors of the hypothalamus and pituitary.
Hypothalamus
Somatostatin -
+ GHRH
Anterior pituitary gland
GH
Liver
Cartilage and bone
growth
Muscle and other
organs:
-Protein synthesis
and growth
Adipose Tissue
-lipolysis
- release of FFAs
Most Tissues
glucose utilization
- blood glucose
Hypothalamus
GHRH
Somatostatin
Anterior
Pituitary
Growth Hormone (GH)
Liver
Adipose Tissue
IGF-1 synthesis
and release
Gluconeogenesis
Glycogen synthesis
-Oxidation of
fatty acids
Lipolysis
Bone
Bone and
cartilage
growth
Muscle
Glucose
uptake
Protein
synthesis
Amino acid
uptake
GROWTH HORMONE
Promotion of secretion
Regulation of secretion
1. HYPOGLYCEMIA (low blood sugar)
2. decreased blood fatty acids
3. increased blood amino acids
4. deep sleep
hypoglycemia
hyperglycemia
inhibits GH-IF
secretion
Inhibits GH-RF
secretion
HYPOTHALAMUS
Inhibition of secretion
1. HYPERGLYCEMIA (high blood sugar)
2.
3.
4.
5.
6.
increased blood fatty acids
decreased blood amino acids
REM sleep
obesity
severe emotional states
GH-RF
GH-IF
secretion on
ANTERIOR PITUITARY GLAND
growth hormone
Actions
1. increased cellular uptake of amino acids = increased protein synthesis = growth/maintenance
2. increased lipolysis and gluconeogenesis for energy, leading to hyperglycemia = diabetogenic effect
secretion off
Growth
hormone
Growth factors
http://www.maniacworld.com/worlds_tallest_man.htm
People with this disease
can also live a normal life
like us. They too can get
married and have kids.
This is a picture of two
dwarfs who are happily
married with each other.
PiCtUrEs
This is a picture of
two dwarfs that
are at work.
Dwarfs can also
make friends.
They have friends
who aren’t dwarfs
too.
Back to Description
Regulating blood osmolarity
If amount of
dissolved
material in
blood too
high, need to
dilute blood
Dehydration
Osmotic concentration
of blood increases
Negative
feedback
Lowers
blood
volume
& pressure
Osmoreceptors
Negative
feedback
ADH synthesized
in hypothalamus
ADH
Increased
water
retention
Reduced
urine
volume
ADH released from
posterior pituitary
into blood
Increased
vasoconstriction
leading to higher
blood pressure
Antidiuretic Hormone
Oxytocin
•
Two target tissues both involved in
neuroendocrine reflexes
Pituitary Gland
Growth Hormone (GH)
Too much Growth Hormone
•
•
•
Acromegaly:
(↑ GH) irreversible
enlarged cranium
and jaw, bulging
forehead, thick lips,
big tongue
enlarged cranium and jaw,
Acromegaly
Effect of growth hormone
Dwarfism
By Amy Evans
PeDiGrEe
AnD cHaRt
BaCk To InHeRiTaNcE
Control of ADH release …cont.
3.  arterial blood pressure, due to  blood volume   ADH.
4. Age:   ADH secretion  water retention & hyponatremia.
5. Pain, emotional stress & physical trauma   ADH secretion.
6. Drugs, e.g. morphine, barbiturates, & nicotine   ADH
secretion.
7. Alcohol   ADH secretion.