The endocrine system
Major Endocrine Glands
What is a target cell?
15.1 Endocrine glands
Circulating and local hormones
•Circulating hormones enter the blood.
•Paracrine hormones act on neighboring cells.
•Autocrine hormones act on the secreting cell.
HormonesReceptors
•Signal Chemicals
•Made in endocrine cells
• Transported via blood
•Receptors on target cells
Long Distance Communication: Endocrine Hormones
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 secreted into the blood acting on downstream target tissues.
• Paracrine – hormones secreted into the interstitial space acting at nearby cells.
• Autocrine – 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 hormoneAT: angiotensin II; LH: luteinizing hormone
Fatty acids
Cholesterol
cholesterol esterase: activated by AT in ZG (IP3-DAG) ACTH in ZF (cAMP)LH in gonads (cAMP)
MITOCHONDRIONmatrix
Pregnenolone SER
Cholesterol esters
storagevacuole
Cholesterol
Acetyl CoA
LDLCholesterolfrom plasma
ACAT
biosynthesis
AT (ZG) ACTH (ZF) LH (gonads)
StAR
outer membrane
inner membrane
Steroidogenic acute regulatory protein
P-450scc: ACTH-activated: ZFAT-activated: ZGLH-activated: gonads
Figure 2. Initial events common to the biosyn-thesis of steroid hormones
inhibited by: AT, ACTH , LH
mRNA production;Preproinsulin genetranscription1
Figure 5. Structural components (italicized) of the pancreatic -cell involved in glucose-induced biosynthesis and release of insulin.
Glucoseuptake
Transport ofproinsulin to Golgi
3vesiclesTransfer
Synthesis of preproinsulin;Uptake into ER;Excision of signal peptide;Disulfide bonds formed
2Endoplasmicreticulum
Microfilaments
Golgi
Proinsulin to insulin;Packaging of insulin
4
Insulin storage5
Microtubules
Secretorygranules
Ca2+ contractionOf microfilaments
6
........ . Granule fusionwith membrane;Exocytosis of insulin7
Ca2+
Biological structuresNucleus
Mechanism of Hormone Action
Receptor
Protein Kinase A(PKA)
NucleusDNA
Protein Synthesis(Enzymes)
Plasma Membrane
Protein Hormones(cAMP second messenger)
Protein Hormones(cAMP second messenger)
CR
R-ERProtein Synthesis
Mitochondria
S-ERSteroid Synthesis
LH
G
Adenylate Cyclase
Mechanism of Hormone Action
Receptor
Protein Kinase A(PKA)
NucleusDNA
Protein Synthesis(Enzymes)
Plasma Membrane
Protein Hormones(cAMP second messenger)
Protein Hormones(cAMP second messenger)G
Adenylate Cyclase
CR
cAMP
LH
ATP cAMP
CR
R-ERProtein Synthesis
Mitochondria
S-ERSteroid Synthesis
C
RcAMP
Mechanism of Hormone Action
Receptor
Protein Kinase A(PKA)
NucleusDNA
Histones
Protein Synthesis(Enzymes)
Plasma Membrane
Protein Hormones(cAMP second messenger)
Protein Hormones(cAMP second messenger)G
Adenylate Cyclase
LH
ATP cAMP
(+ PO4)
R-ERProtein Synthesis
Mitochondria
S-ERSteroid Synthesis
mRNA
Mechanism of Hormone Action
Receptor
Protein Kinase A(PKA)
NucleusDNA
Histones
Protein Synthesis(Enzymes) mRNA
Plasma Membrane
Protein Hormones(cAMP second messenger)
Protein Hormones(cAMP second messenger)
Cholesterol
GAdenylate Cyclase
C
RcAMP
LH
ATP cAMP
(+ PO4)
R-ERProtein Synthesis
MitochondriaCholesterolPregnenolone
S-ERSteroid Synthesis
Testosterone
Nonsteroid Hormone ActionNonsteroid Hormone Action
Slide 9.9Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 9.1b
Steroid Hormone ActionSteroid Hormone Action
Slide 9.7Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 9.1a
Action of a steroid hormone
Master control
Master integrator
HYPOTHALAMUS
PITUITARY GLAND
AKA = hypophysis
Infundibulum
Sella turcica
hypothalamus
infundibulum
pituitary gland
sella turcica in sphenoid bone
Sella turcica of the sphlenoid bone
Location of the Pituitary
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
(CRF)
Thyrotropin RF Growth Hor RF Prolactin RF
Pituitary Hormones:
Follicle SH &
Lutenizing Hor.
Thyrotropin SHAdrenocorticoptropin
Hormone (ACTH)
ProlactinGrowth
Hormone
Target Gland or Structure:
Ovaries & Testes
(androgens, estrogen)
Adrenal Gland
(cortisol)
Cells of bodyThyroid Gland
(thyroxine)
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
Hypothalamus
Pituitary gland
Target organ
Hormone A
Hormone B
Releasing factorsInhibitingfactors
Neural input
+
+
+
Positive/Negative Feedback loop
Important Point: Secretions are pulsatile vs. continuous
Hypothalamus
Pituitary gland
Thyroid Gland
TSH
T3(inhibitory)
T4
Thyrotropin RH via dorsomedial nucleus
Neural input
+
+
+
Thyrotrophs (5%)
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
Anterior Pituitary
TRH Somatostatin
Thyrotropin (TSH)
Thyroid gland
Estrogen Growth hormone (GH)
Glucocorticoids
Thyroid hormones (T4 and T3)
Feedback inhibition on
hypothalamus TRH secretion
Feedback inhibition on pituitary TSH
secretion
Complex negative feedbackComplex negative feedback
Controlling centers of the CNS
Neural pathways
HypothalamusHypothalamic hormones
AdenohypophysisAdenohypophysal 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 PituitaryHormones of the Anterior Pituitary
Slide 9.17Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 9.4
Figure 6.8
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 dwarfismtoo 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
Con
trol
of
Pro
lact
in Hypothalamus
Ant Pituitary
Breast
Affe
ren
t Stim
ula
tory
pa
thw
ayTRH Dopamine
PRL
I
I+
+ StressHigher centers
Suc
klin
g st
imul
us
Milk production
+
+
PR
L
Con
trol
of
AC
TH Hypothalamus
Ant Pituitary
Adrenal Gland
CRH
Stress
ACTH
I
+
Cortisol
+
AC
TH
I
II
+
Cor
tisol
Con
trol
of
TS
H
Hypothalamus
Ant Pituitary
Thyroid Gland
TRHDopamine
Somatostatin
TSH
I
I+
T3 + T4
+
TS
HI
II
Higher centres
Con
trol
of
LH &
FS
HIn
Mal
eHypothalamus
Ant Pituitary
TestesLeydig Cells Sertoli cells
GnRH
LH
I
+
Testosterone
+
I
II
FSH
Inhibin
+
+
Con
trol
of
LH &
FS
HIn
Fem
ale
Hypothalamus
Ant Pituitary
Ovary
GnRH
LH
I
+
OestradiolProgesterone
+
I
I+I+
FSH
Inhibin
+
Pituitary & Hypothalamus
Hormones of the Posterior PituitaryHormones of the Posterior Pituitary
Slide 9.22bCopyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 9.5
Con
trol
of
Oxy
toci
n
Hypothalamus
Post Pituitary
Oxytocin
Mammary gland
+
Uterus
+
Higher Centers
Str
etch
rec
epto
rs
Stretch receptors
Con
trol
of
Vas
opre
ssin
Hypothalamus
Post Pituitary
Vasopressin
Blood Vessel
Higher Centers
Stretch receptors
Baroreceptors
Osmoreceptors
H2O
Kidney
ANTI-DIURETIC HORMONE
AKA = vasopressin
Hypothalamic osmoreceptors
Water reabsorption
dehydration
increased interstitial fluid osmotic pressure
stimulation of hypothalamic osmoreceptors( -)
1. WATER REABSORPTION BY KIDNEYS2. decreased perspiration
secretion of ADH from posterior pituitary gland
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
Anterior pituitary gland
+ GHRH
Somatostatin -
GH
Liver
Cartilage and bone growthMuscle and other organs:-Protein synthesis and growth
Adipose Tissue -lipolysis- release of FFAsMost Tissues glucose utilization- blood glucose
Hypothalamus
Anterior Pituitary
Growth Hormone (GH)
Liver BoneAdipose Tissue Muscle
GHRH Somatostatin
IGF-1 synthesis and release
Gluconeogenesis
Glycogen synthesis
-Oxidation of fatty acids
Bone and cartilage growth
Glucose uptake
Protein synthesis
Amino acid uptake
Lipolysis
Promotion of secretion
GROWTH HORMONE
1. HYPOGLYCEMIA (low blood sugar)
2. decreased blood fatty acids3. increased blood amino acids4. deep sleep
Inhibition of secretion1. HYPERGLYCEMIA (high blood sugar)
2. increased blood fatty acids3. decreased blood amino acids4. REM sleep5. obesity6. severe emotional states
Actions 1. increased cellular uptake of amino acids = increased protein synthesis = growth/maintenance2. increased lipolysis and gluconeogenesis for energy, leading to hyperglycemia = diabetogenic effect
Regulation of secretion
inhibits GH-IFsecretion
Inhibits GH-RF secretion
HYPOTHALAMUS
hypoglycemia hyperglycemia
GH-RF GH-IF
ANTERIOR PITUITARY GLAND
growth hormone
secretion on secretion off
Growthhormone
Growth factors
http://www.maniacworld.com/worlds_tallest_man.htm
PiCtUrEs
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.
Dwarfs can also make friends.
They have friends who aren’t dwarfs
too.This is a picture of
two dwarfs that are at work.
Back to Description
Regulating blood osmolarity
If amount of dissolved material in blood too high, need to dilute blood ADH
Dehydration Lowers blood volume & pressure
Increased waterretention
Increasedvasoconstrictionleading to higherblood pressureReduced
urine volume
Osmotic concentrationof blood increases
ADH synthesized in hypothalamus
ADH released from posterior pituitary into blood
Osmoreceptors NegativefeedbackNegative
feedback
Antidiuretic Hormone
Oxytocin
• Two target tissues both involved in neuroendocrine reflexes
Pituitary Gland Growth Hormone (GH)
•Acromegaly:
• (↑ GH) irreversible
•enlarged cranium and jaw, bulging forehead, thick lips, big tongue
Too much Growth Hormone enlarged cranium and jaw,
Acromegaly
Effect of growth hormone
Dwarfism
By Amy Evans
PeDiGrEeAnD cHaRt
BaCk To InHeRiTaNcE
Control of ADH release …cont.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.