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1
The Endocrine System
2
Outline
• Types of Regulatory Molecules• Endocrine Glands and Hormones• Paracrine Regulation• Hormones That Enter Cells• Hormones That Do Not Enter Cells• Posterior and Anterior Pituitary Gland• Thyroid and Parathyroid Glands• Adrenal Glands• Other Endocrine Glands
3
SIGNALING AGENTS & FACTORS
Neurotransmitters
Peptides
Oxygen-based molecules, e.g., NO
Prostanoids
Hormones
Cytokines ( some are Chemokines)
Extracellular-matrix molecules
Nutrients & metabolites
Mechanical stimuli, e.g., fluid shear
Cell-surface glycoproteins
Hormones from endocrine cells & organs are part of a much larger picture of the outside controls on cells
Heat, osmolarity, exogenous chemicals, etc
ENDOCRINE
4
Types of Regulatory Molecules
• Hormone – A regulatory chemical secreted into the blood by an endocrine gland, or an organ exhibiting endocrine function.
• Target Cells respond to hormone– Neurohormone – A chemical messenger
secreted by neuron into the blood rather than the synaptic cleft.
• Paracrine - regulatory molecules work without being transmitted by the blood – not endocrine
• Pheromone - communication messengers
5
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Axon Neurotransmitter
Endocrine gland
Paracrine regulator
Receptor proteins
Hormonecarried by blood
Target cell
6
Endocrine Glands and Hormones• Hormones secreted by the endocrine glands belong to four
chemical categories:– Polypeptides - short chains of amino acids less than 100
amino acids (insulin & ADH)– Glycoproteins- longer than100 A.A. with carbs (FSH and LH)– Amines - Amines – A.A. derived from tyrosine and
tryptophan – epinephrine and norepinephrine and melatonin – Steroids - lipids derived from cholesterol
sex steroids - testosterone, estadiol, progesterone, and cortisol – secreted by testes, ovaries, placenta and adrenal cortex
Corticosteroids - adrenal cortex cortisol and aldosterone (regulates glucose and salt balance)
– All hormones can be categorized as lipophilic (fat soluble) or hydrophilic (water soluble).
7
Endocrine Glands and Hormones• Neural and endocrine interactions
– Endocrine system also interacts and cooperates with the nervous system to regulate the activities of the other organ systems of the body.
– Secretory activity of many endocrine glands controlled by nervous system like
Adrenal medulla, posterior pituitary, and pineal gland
major site for neural regulation is the brain’s regulation of the anterior pituitary by the hypothalmus
However many are not under neural control
8
Human Endocrine Systemmajor glands
9
cvlAl
re
uo
- - - - - - - diaphragm
Parathyroids
Adrenal cortex
Thyroid
Pituitary anterior
Pancreas
Gonads
ENDOCRINE ORGANS I
10
[ non-epithelial origin ]
cvlAl
re
uo
- - - - - - - diaphragm
Parathyroids
Adrenal cortex
Thyroid
Pituitary anterior
Pancreas
Gonads
ENDOCRINE ORGANS II
[Pineal]
[Heart]
[Adrenal medulla]
[Kidney]
[Placenta]
Plus neuroendocrine cells developed within mature gut, airway, etc epithelia
[Pituitary, posterior & Brain]
[Adipose tissue]
11
TYPICAL ENDOCRINE GLAND - Context
hormone release
vessels
Clumps of endocrine cells
blood
control
Capillary diffusion
TARGET ORGAN
Target cells, with receptors for binding
12
transport3
4 5
Target cells’ response
6
Feedback
12
GLAND(S) WHERE CELL TYPES HORMONES SPECIAL
Thyroid Neck Follicular cells C cells
Thyronine Calcitonin
Follicles for storage
Parathyroid Neck Chief cells Parathormone /PTH
Small
Adrenal medulla
Over kidney
Chromaffin cells
Epinephrine Norepinephrine
Nerve fibers
Adrenal cortex
Over kidney
Zona glomerulosa Zona fasciculata Zona reticularis
Mineralocorticoids Glucocorticoids Sex steroids
Pineal Brain’s center
Pinealocytes Melatonin Connected for light drive
Zones
ENDOCRINE ORGANS I
13
GLAND(S) WHERE CELL TYPES HORMONES SPECIAL
Pituitary posterior
Axons of PV & SO hypothal. neurons
Oxytocin Vasopressin /ADH
Extension of brain
Pancreas Left upper quad
Beta, Alpha, Delta, PP cells
Insulin Glucagon Somatostatin Pancr Peptide
Gonads Pelvic/ Scrotal
Granulosa, Theca Lutein, & Leydig
Sex steroids Inhibin
Placenta Uterus Syncytiotrophoblast Female: for amplified hormonal responses
Female: cyclic
Pituitary anterior
Below brain
MTs STs GTs THs CTs
Blood drains hypothal.-pituitary for control
Prolactin GH LH FSH TSH ACTH
Below brain
Islets
+Pituicytess
ENDOCRINE ORGANS II
14
Paracrine Regulation
• Signaling between cells - Local effect and short-lived occurs in many organs
• Regulatory molecules– cytokines - regulate different cells of the
immune system– growth factors - promote growth and cell
division in specific organs – stimulate cell division at target cells
15
Paracrine Regulation• Prostaglandins – most diverse group of paracrine regulators• participate in regulation of:
– immune system – inflammation, pain and fever– reproductive system – reproductive function ovulation,
labor, – digestive system – inhibit gastric secretions, incrfease
motility and fluid absorption – respiratory system - blood vessels constriction and dilation
in lungs– circulatory system - blood platelets in blood clotting– urinary system - renal blood flow vasodilation increasing
urine excretion• Prostaglandin synthesis inhibited by aspirin.
– nonsteroidal anti-inflammatory drug Ibuprofen Work to inhibit inflammation and pain by inhibiting
enzyme necessary to produce prostaglandins – (cyclooxygenase -2)
16
Hormones That Enter Cells
• Lipophilic hormones pass through the target cell’s plasma membrane and bind to intracellular receptor proteins.
– hormone receptor complex then binds to specific regions of DNA
activate genes and regulate target cells
17
Steroid Hormone Action
18
Hormones That Do Not Enter Cells
• Hormones that are too large or too polar to cross plasma membranes include all of the peptide and glycoprotein hormones, as well as catecholamine hormones epinephrine and norepinephrine.
– bind to receptor proteins located on the outer surface of the plasma membrane
cyclic AMP second-messenger system IP3/CA++ second-messenger system
19
Action of Epinephrine on a Liver Cell
1. Epinephrine is lipophobic and needs to bind to specific receptor proteins on cell surface.
2. Acting through intermediary G proteins the hormone bound receptor activates the enzyme adenenylyl cyclase which converts ATP to cAMP
3. Cyclic AMP performs as a 2ndary messenger and activates protein kinase-A an enzyme that was previously inactive
4. Protein kinase–A phosphorylates and activates the enzyme phosphorylase which catalyses the hydrolysis of glycogen into glucose.
20
IP3/CA++ Second-Messenger System
1. The hormone epinephrine binds to specific receptor proteins on the cell surface.
2. Acting through G- proteins, the hormone-bound receptor activates the enzyme phospholipase C, which converts membrane phospholipids into inositol triphosphate (IP3)
3. IP3 diffuses thru the cytoplasm
and binds to receptors on the endoplasmic reticulum
4. The binding of IP3 to the receptor stimulates the endoplasmic reticulum to release Ca++ into the cytoplasm
5. Some of the released Ca++ binds to the receptor protein called calmodulin
6. The Ca++/Calmodulin complex activates other intracellular proteins – producing the horomone effects
21
Primary endocrine organs
• Hypothalamus and pituitary gland secrete hormones and regulate other endocrine organs. They are the main regulatory organs of the endocrine system.
22
Hypothalamus
• Located below the thalamus and above the pituitary gland (=epiphysis)
• Regulates the pituitary gland secretions through two different mechanisms
23
Hypothalamus - neurohypophysis
• 1- Neurons, receiving information from receptors, fire APs which travel down to the post pituitary gland and stimulate the release of stored neurohormones – Oxytocin (OT) and anti-diuretic hormone (ADH)
24
Hormones of the posterior pituitary
Regulation Hormone Target organ Action Pathology
Reflex Oxytocin - Uterus (smooth muscle)- breast tubules (smooth muscles)
-labor and delivery
- milk-let down
----
Reflex (osmoreceptor) ADH (vasopressin)
- DCT in kidney tubules
- promote H2O reabsorption
- not enough: diabetes insipidus- too much: ↑ BP?
25
Hypothalamus – adenohypophysis
• 2- Upon stimulation, secretory cells located in the hypothalamus secrete “releasing” hormones which travel down a capillary bed toward the anterior pituitary gland (adenopituitary). Each type of releasing hormones will stimulate the secretion and release of a pituitary hormone.
• Hormones which control the secretion of other hormones are tropic hormones (found in hypothalamus and pituitary gland
26Figure 6.5
Hormones of the hypothalamus and anterior pituitary gland
27Figure 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
28Figure 23-17
Same Individual with Acromegaly (evolution over 20 years)
29Figure 6.6
Mechanism of control
30
HYPOPHYSIS/ Pituitary gland
Pituitary stalk
Posterior lobe
Hypoth alamus
Anterior lobe
Dura
IIIrd Ve
Interm
ediate lo
be
31
Pars nervosa Infundibular process
Pars intermedia
PITUITARY SUB-DIVISIONS
Hypothalamic SO & PV nuclei
Hypothalamic median eminenceADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem neural part of stalk
1
3
2
1
2
3
32
Unlike some other endocrine cells, those of the anterior pituitary separate their supplying a hormone from the detection of the need for the hormone.
The sensitivity to need is performed by hypothalamic neurons, which can coordinate requirements for several hormones with drives, and events outside the person.
Anterior-pituitary cells & hormones
The system also allows for control by inhibitory factors, as well as + driving hormone-releasing factors
33
HYPOTHALAMO-HYPOPHYSEAL Portal flow
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe capillaries
Dura
Hypothalamic capillary bed
Neurosecretory neurons
Veins
1
2
3
4
5
A portal flow takes venous blood drained from one organ and uses it as a supply to another organ, e.g., gut to liver
34
HYPOTHALAMO-HYPOPHYSEAL Portal flow
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe capillaries
Hypothalamic capillary bed
Neurosecretory neurons
Veins
1
2
3
4
5
Portal flow carries factors from hypothalamic neurons to pituitary anterior-lobe cells
E.g.,TH-RF from neuron causes
Thyrotroph to release TSH
35
Superior arteries
Portal drainage
Hypothalamus
Anterior lobe capillaries
Hypothalamic capillary bed
Neurosecretory neurons
Veins
1
2
3
4
5
Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs
Blood drains hypothalamus-pituitary for control by RFs, etc
Prolactin PRL Growth hormone GH Luteinizing hormone LH Follicle-stimulating hormone FSH Thyroid-stimulating hormone TSH Adrenocorticotrophic hormone ACTH
Anterior-pituitary cells & hormones
36
Mammotrophs MTs
Somatotrophs STs
Gonadotrophs GTs
Thyrotrophs THs
Corticotrophs CTs
Blood drains hypothalamus-pituitary for control by RFs, etc
Prolactin PRL
Growth hormone GH
Luteinizing hormone LH/ICSH Follicle-stimulating hormone FSH
Thyroid-stimulating hormone TSH
Adrenocorticotrophic hormone ACTH cleaved from pro-opio-melanonocortin/ POMC
Anterior-pituitary cells & hormones
Acidophil
Basophil
37
Anterior-pituitary cells 2Mammotrophs MTs
Somatotrophs STs
Gonadotrophs GTs
Thyrotrophs THs
Corticotrophs CTs
Prolactin PRL
Growth hormone GH
Luteinizing hormone LH FSH
TSH
ACTH
Acidophil Basophil Chromophobe
Chromophobes stain weakly, in comparison to CHROMOPHILS - Acidophils & Basophils
Folliculo-Stellate cells lie amongst the glandular cells; doing what?
38
Anterior-pituitary cells 3
Corticotrophs CTs ACTH
but by selective enzymatic cleavage of a larger 32kDa precursor - pro-opiomelanocortin, also made in the hypothalamus and elsewhere, and there serving to provide other hormones & neurotransmitters
Pro-opiomelanocortin
ACTH
Pro-ACTH -LPH
-Endorphin
-MSH
SP
simplified
POMC ~ Pro-opiomelanocortin
39
Anterior-pituitary cells 4Selective enzymatic cleavage of the precursor - pro-opiomelanocortin, provides other hormones & transmitters
ACTH
-Endorphin
Pro-opiomelanocortinSP
NT 1-76
-LPHACTH
-LPHACTH
-LPH
NT 1-49
JP
-MSH
-MSH -MSH
elaborate
MSH ~ Melanocyte-stimulating hormone
NT ~ amino-terminal peptides
LPH ~ Lipotropic hormonePro-hormone convertase 1
Pro-hormone convertase 1
Pro-MSH
Pro-MSH
After Reudelhuber TL. J Clin Invest 2003;111:1115-1116
40
NEUROHYPOPHYSIS
Pars nervosa
Hypothalamic SO & PV nuclei Supraoptic & Paraventricular nuclei
Hypothalamus 1
2
3
Inferior arteries
Veins
Release of hormone is separated from production
*
*
*
* Neural stalk
Optic chiasm
41
NEUROHYPOPHYSIS
Pars nervosa
Hypothalamic SO & PV nuclei Supraoptic & Paraventricular nuclei
Hypothalamus 1
2
3
Inferior arteries
Veins
*
*
Neural stalk
Optic chiasm
Note - the supraoptic nucleus is above the optic nerve & chiasm, but closer to the chiasm is the small suprachiasmatic nucleus (relaying the darkness stimulus indirectly to the pineal gland).
42
NEUROHYPOPHYSIS
Pars nervosa axons, terminals, pituicytes & capillaries
Hypothalamic SO & PV nucleiHypothalamus
Infundibular stem neural part of stalk - axons & glia
1
2
3
Neurosecretory neurons producing oxytocin & vasopressin/ADH
Inferior arteries
Veins
Release of hormone is separated from production
* *
*
*
43
NEUROHYPOPHYSIS
Hypothalamic SO & PV nucleiHypothalamus Neurosecretory neurons producing oxytocin & vasopressin/ADH
Inferior arteries
Veins
Hormone travels down the axon bound to the carrier protein - neurophysin, from which it is cleaved for release
*
*
44
SUCKLING REFLEXHypothalamic SO & PV neuron activation
Hypothalamus
*
BREAST
Myoepithelial-cell contraction
Sensory response
Oxytocin releaseStimulus1
23
4
56
7 Milk ejectionVascular transfer
45
PITUITARY Mid-sagittal section of 1-m embryo
STOMODEUM
PHARYNGEAL ARCHES
PITUITARY
RATHKE’S POUCH
starting in oral ectoderm
BRAINI II
46
PITUITARY DEVELOPMENT II Neural-tube diencephalic ectoderm
Oral-pharyngeal lining ectoderm
IIIrd Ve
Rathke’s pouch
Pars tuberalis
Pars distalis
Pars intermedia
Pars nervosa
Infundibular stem
Hypothalamus
ADENOHYPOPHYSIS
NEUROHYPOPHYSIS
47
PITUITARY DEVELOPMENT II
Pars tuberalis
Pars distalis
Pars intermedia
Pars nervosa
Infundibular stem
Hypothalamus
Pars nervosa Infundibular process
Pars intermedia
Hypothalamic SO & PV nuclei
Hypothalamic median
eminenceADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem neural part of stalk1
3
2
1
2
3
CystsCysts in Pars intermedia - remnants of Rathke’s pouch lumen?
Rathke’s pouch lumen
48
Pars nervosa/ Infundibular process
Pars intermedia
Hypothalamic SO & PV nuclei
Hypothalamic median eminence
ADENOHYPOPHYSIS
Pars distalis
Pars tuberalis
NEUROHYPOPHYSIS
Infundibular stem/ neural part of stalk1
3
2
1
2
3
CystsCysts in Pars intermedia - remnants of Rathke’s pouch lumen?
49
Posterior Pituitary Gland
• Pituitary gland hangs by a stalk from the hypothalamus of the brain.
– anterior pituitary - appears glandular– posterior pituitary - appears fibrous
• Neurons produce antidiuretic hormone (ADH) and oxytocin.
– stored in, and released from, the posterior pituitary gland in response to neural stimulation from the hypothalamus
50
Effects of ADH
51
Anterior Pituitary Gland• Develops from a pouch of epithelial tissue that pinches off the
roof of the embryo’s mouth.– produces the hormones it secretes:
growth hormone (GH) stimulates muscles and bones to grow
adrenocorticotropic hormone (ACTH) regulates glucose homeostasis
thyroid-stimulating hormone (TSH) stimulates the production of thyroxin by thyroid gland
luteinizing hormone (LH) ovulation and testosterone production in testes
follicle-stimulating hormone (FSH) develops ovarian follicle and sperm in males
prolactin (PRL) stimulates mammary glands to produce milk melanocyte-stimulating hormone (MSH) synthesis and
dispersion of melanin pigment
52
Major Pituitary Gland Hormones
53
Anterior Pituitary Gland
• Hypothalamic control of anterior pituitary gland secretion
– Neurons in the hypothalamus secrete releasing hormones and inhibiting hormones into blood capillaries at the base of the hypothalamus.
Each hormone delivered by hypothalamohypophysial portal system regulates secretion or inhibition of a specific anterior pituitary hormone.
54
Neurons in the hypothalamus secretes hormones that are carried by short blood vessels directly to the ant. Pituitary gland, where they either stimulate
or inhibit the secretions of the ant pituitary hormonesCell body
Axons toprimarycapillaries
Primarycapillaries
Pituitary stalk
Posterior pituitary
Anterior pituitary
Secondarycapillaries
Portalvenules
55
Anterior Pituitary Gland
• Negative feedback inhibition acts to maintain relatively constant levels of the target cell hormone.
– Positive feedback cannot maintain constancy of the internal environment.
56
Negative Feedback Inhibition
Hormones secreted by some endocrine glands feed back to inhibit the secretion of hypothalamic releasing hormones and anterior pituitary hormones
57
Thyroid and Parathyroid Glands
• Thyroid gland– Shaped like a shield and lies just below the
Adam’s apple in the front of the neck. Thyroxine helps set basal metabolic rate
by stimulating the rate of cell respiration. In children, thyroid hormones also
promote growth and stimulate maturation of the central nervous system.
unique function in amphibians - metamorphosis from larvae into adults
58
Regulation of Thyroxine Secretion
59
Thyroid and Parathyroid Glands
• Parathyroid gland and calcium homeostasis– four small glands attached to the thyroid
produces parathyroid hormone (PTH)one of only two hormones in humans
that are absolutely essential for survivalstimulates osteoclasts in bone to
dissolve calcium phosphate crystals and release Ca++ into the blood
60
Regulation of Blood Calcium Levels
61
Calcium Metabolism:
Figure 23-20: Calcium balance in the body
62Figure 19.20
63
THYROID GLAND
Follicular cells simple cuboidal epithelium
Colloid / Thyroglobulin
glycoprotein = PAS+
Follicles for storage
C cells/ Parafollicular cells
Capillaries
In the section, the follicles do not hold their spherical shape this well, and the colloid displays knife chatters and variable staining
64
THYROID GLAND: Physiological variablity
Follicular cells high cuboidal when very active; squamous when inactive
Colloid / Thyroglobulin less in active state, excessive in goitre
Follicles - size
varies inversely with activity
C cells/ Parafollicular cells for calcitonin
Capillaries
65
GOLGI
Amino acids
Sugars
Iodine
Thyroglobulin
Endocytosis
Cleavage
Release of hormones T3 & T4
Synthesis & iodination of thyroglobulin
THYROID FOLLICULAR CELL
TSH
66
Goiter
• Both hypo and hyperthyroidism can have goiter as a symptom
• Goiter is a swelling of the neck due to hypertrophy of the thyroid gland
• How can one explain that?
67
Goiter in hypothyroidism
• Most often due to a lack of dietary iodine
• The thyroid hormone is unable to synthesize a functional thyroid hormone (T3 and T4)
• The person express symptoms of hypothyroidism
• The nonfunctional T3/T4 cannot promote a negative feedback on TRH and TSH
the hypotalamus and pituitary gland increase their secretions the thyroid gland is stimulated to secrete more T3 and T4 …
• In children, the lack of functional T3/T4 result in cretinism, a form a mental retardation
68
Goiter in hyperthyroidism
• The cells secreting TRH or TSH on the hypothalamus and pituitary gland (respectively) have become abnormal and no longer are sensitive to the negative feedback they continue to secrete TRH or TSH continuous stimulation of the thyroid gland with excess thyroid hormones being formed
symptoms of hyperthyroidism
69
PARATHYROID GLAND
Oxyphil cells
Chief cells
Characteristic is the lack of obvious general structural features
Small, pale, resemble lymphocytes, but have more cytoplasm
Larger, eosinophilic, darker nuclei, packed with mitochondria
70
PARATHYROID GLAND
OXYPHIL CELLS
CHIEF CELLShave membrane calcium sensors to respond to low Ca2+ by releasing parathyroid hormone /PTH. PTH stimulates osteoclasts to release Ca2+ from bone & has conserving renal effects
derivatives of Chief cells
71
Osteoclast
Ruffled border agitating released enzymes & acid
Eaten-out hole is a Howship’s lacuna
BONE REMODELING
Osteoclasts as a team eating out a resorption tunnel
Sealing ring of tight attachment to bone
BONE MATRIX
BONE
72
ONCOCYTIC CONVERSION
As cuboidal epithelia and glands age, a few of their epithelial cells lose most of their normal organelles and fill up with mitochondria. Mitochondria-rich cells are eosinophilic.
This event results in two classes of cell:
those that are functioning normally and need many mitochondria - gastric parietal cells, renal proximal-tubular cells, striated-duct cells, etc; &
non-functional mitochondria-stuffed cells in older epithelia. These have acquired two names: the usual - oncocyte, and, as an exception, the archaic oxyphil cell in the parathyroids. & Hurthle cells
in thyroid
:
73
Adrenal Glands
• Adrenal glands are located above each kidney.
– Each gland composed of inner portion (adrenal medulla) and outer layer (adrenal cortex).
• Adrenal medulla– receives neural input from axons of
sympathetic division of the autonomic nervous system, and secretes epinephrine and norepinephrine in response
74
Adrenal Glands
• Adrenal cortex– Hormones from adrenal cortex are
collectively referred to as corticosteroids. Cortisol maintains glucose homeostasis,
and modulates some aspects of the immune response.
Aldosterone stimulates the kidneys to reabsorb Na+ and secrete K+ into the urine.
75
Adrenal Glands
76
Cortex
Medulla
Capsule
Adrenal vein
ADRENAL/SUPRARENAL GLAND
The adrenal embryologically is a composite of the:
medulla derived from ectoder mal neural-crest cells; &
cortex formed from mesoder m next to the mesonephros
77
ADRENAL CORTEXCortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
]
]
small balls of cells
straight bundles of paler cells
cords of cells in a network
sparse Stroma of reticular fibers & vessels
Capsule
78
ADRENAL CORTICAL HORMONES
Cortex
Zona glomerulosa
Zona fasciculata
Zona reticularis
]
]
makes mineralocorticoids, e.g., aldosterone
makes glucocorticoids, e.g., cortisol
makes sex steroids, e.g., androstenedione
79
Zona glomerulosa regulated by Renin-angiotensin system
Zona fasciculata driven by ACTH
Zona reticularis driven by LH & ACTH
]
]
to make & release mineralocorticoids
to make glucocorticoids
to make sex steroids* & glucocorticoids
Zona-fasciculata steroid-synthesizing cell
Cholesterol droplets (often dissolved out)
Smooth ER, often tubular (bag-of-worms visual effect)
Mitochondria with tubular cristae
dehydroepiandrosterone*
80
Zona glomerulosa regulated by Renin-angiotensin system
mineralocorticoids
glucocorticoids
sex steroids* & glucocorticoids
]
]Zona reticularis driven by LH & ACTH
Zona fasciculata driven by ACTH
81
Zona-fasciculata steroid-synthesizing cell
Cholesterol droplets (often dissolved out)
Smooth ER, often tubular (bag-of-worms visual effect)
Mitochondria with tubular cristae
Inner mitochondrial membrane has a P450 enzyme for steroid biosynthesis
82
Zona glomerulosa ]
JG cellsRenin
Converting Enzyme
DISTAL TUBULE
Angiotensinogen
Angiotensin I
Angiotensin II
Aldosterone
Vasoconstriction
Sodium + water reabsorption (so blood pressure up)
JUXTAGLOMERULAR APPARATUS 6
Outside kidney
Renin is a protease
83
Aldosterone
Zona glomerulosa
JG cellsRenin
Converting Enzyme/ ACE
Angiotensinogen
Angiotensin I
Angiotensin II
Vasoconstriction
RENIN-ANGIOTENSIN SYSTEM
DISTAL TUBULE
Outside kidney
ACE is in many tissues, and the angiotensin II receptor is widespread, so that the RA system is very endocrine in affecting most of the body, not just vessels, adrenal & kidney
84
ADRENAL MEDULLA
Chromaffin cells
Sympathetic axons
Central vein
Occasional neuron
terminating mainly on chromaffin cells
Chromaffin cells so named, because of chromaffin reaction - a brown darkening of medulla seen when catecholamines react with dichromate & other oxidising agents
85
ADRENAL MEDULLA
Chromaffin cells make epinephrine & norepinephrine
Sympathetic axons
Central vein
Occasional neuron
terminating mainly on chromaffin cells
Epinephrine & norepinephrine are catecholamines stored, in association with the protein chromogranin, in dense-cored granules/ vesicles. E & NE augment sympathetic autonomic nervous-system actions
86
CATECHOLAMINE SYNTHESIS
Chromaffin cells make epinephrine & norepinephrine
TYROSINE
tyrosine hydroxylase
DOPA/Dihydroxyphenylalanine
DOPAMINE
aromatic L-amino acid decarboxylase/AADC
dopamine -hydroxylase/DBH
NOREPINEPHRINE
EPINEPHRINE/Adrenalin
phenylethanolamine-N-methyltransferase
[rate-limiting?]
87Figure 6.12b
88Figure 21.15
89
Adrenal gland hormones
Regulation Glands Hormones Target organs
Action Pathology
Reflex Adrenal medulla Epinephrine ANS target organs
Fight/flight Stress
Blood Pressure Adrenal cortex - Mineralocorticoid = aldosterone
DCT from renal tubule
- promote sodium reabsorption
Not enough" Addison disease
CRH ACTH Glucocorticoid = cortisone
Many cells Mobilize fuels – stress adaptation
Excess hormone: Cushing syndrome
GnRH GN Estrogen Testosterone
Sexual organs - Sex organ maintenance- Gamete development
Infertility
90
91
Pancreas
• Located adjacent to the stomach and is connected to the duodenum by the pancreatic duct.
– Secretes bicarbonate ions and a variety of digestive enzymes into small intestine.
cells of islets of Langerhans secrete insulin, and cells secrete glucagon.
antagonistic Insulin lowers while glucogen
raises blood glucose.
92
PANCREASDuodenum
Exocrine acini digestive enzymes
Lobule
}
Endocrine islet metabolic hormones
Ducts alkaline ions
Enteroendocrine cells hormones
93
Islet of Langerhans
ISLET: Cell types & products
Beta cell - insulin (majority)
Alpha cell - Glucagon
Delta cell - Somatostatin
PP cell - Pancreatic polypeptide
Beta & Alpha cells are directly sensitive to glucose level
94
Antagonistic Actions of Insulin and Glucagon
95
Glucose regulation
• Glucose level controlled by insulin and glucagon
• Insulin promotes a decrease in blood glucose
• Glucagon promotes an increase in blood glucose
96
Glucose regulation
97Figure 3.21
Fate of glucose
98
Diabetes mellitus
• Type I: autoimmune disease beta cells of the islets of Langerhans are destroyed by antibodies
• Type II: The cells become insulin-resistant glucose does not enter the cells as readily
99
Diabetic foot
100
Other Endocrine Glands
• Ovaries and testes– produce androgen
secondary sexual characteristics• Pineal gland
– secretes melatonin regulates biological clocks
101
Other Endocrine Glands
• Molting and metamorphosis in insects– Hormone secretions influence both
molting and metamorphosis in insects. Brain hormone stimulates production of
ecdysone (molting hormone).high levels cause molting to occur
juvenile hormonehigh levels prevent transformation to
an adult
102
Other Endocrine Glands
• Endocrine disrupting chemicals– chemicals that interfere with hormone
function Any chemical that can bind to receptor
proteins and mimic the effects of the hormone is called a hormone agonist.
Any chemical that binds to receptor proteins and has no effect, but blocks the hormone from binding is a hormone antagonist.
103
Cerebral Cortex
Cerebellum
Pineal gland
Brain Stem
Eye & optic nerve
Central sympathetic pathways
Suprachiasmatic nucleus
Thoracic cord
Sympathetic preganglionic
S Cervical ganglion
Sympathetic postganglionics
PINEAL ACTIVATION PATHWAY
13
4
2
5
7
Darkness increases HIOMT enzyme to make melatonin
HydroxyIndole-O-MethylTransferase
1 7
6
104
Cerebral Cortex
Cerebellum
Pineal gland
Brain Stem
Eye & optic nerve
Central sympathetic pathways
Suprachiasmatic nucleus
Thoracic cord
Sympathetic preganglionic
S Cervical ganglion
Sympathetic postganglionics
PINEAL ACTIVATION PATHWAY
13
4
2
5
6
1 7
7 melatonin
light offMelanopsin in retinal ganglion cells is the photosensitive mediator
105
Cerebral Cortex
Cerebellum
PINEAL GLAND
Brain Stem
Eye & optic nerve
Central sympathetic pathways
Suprachiasmatic nucleus
Thoracic cord
Sympathetic preganglionic
S Cervical ganglion
Sympathetic postganglionics
PINEAL ACTIVATION PATHWAY
13
4
2
5
7
Darkness increases HIOMT enzyme to make melatonin HydroxyIndole-O-MethylTransferase
6
melatonin
light off
106
cvlAl
re
uo
- - - - - - -
ENDOCRINE ORGANS II
Plus neuroendocrine cells developed within mature gut, airway, etc epithelia
[Kidney]
[Heart] ANF
EPO Renin
VIP Gastrin Secretin, etc
Gonads
[Placenta]hCG Estrogen Progesterone
Sex steroids
[Adipose tissue]
Leptin
107
ATRIAL HEART & ANF
Atrial myocytes have a well developed Golgi complex and secretory granules
Reticular fiber
Atrial Natriuretic Factor (ANF) in the granules STIMULATES:
diuresis; sodium excretion (natriuresis); vasorelaxation;
& INHIBITS the Renin-Angiotensin system & aldosterone secretion
108
Enteroendocrine cell types I
Enteroendocrine cell small, pale, few; granules are located basally for release into the lamina propria
Entero is misleading because: some cell types are confined to the stomach; and peptides & amines are signaling agents in other epithelia and other systems e.g. brain
G cell - gastrin
S cell - secretin
I cell - cholecystokinin
ECL cell - histamine
D cell (antral) - somatostatin
EC cell - serotonin
A cell - ghrelin
109
Enteroendocrine cell types II
Motilin cell: why not ‘M’ cell? There already is one, involved in immunity
G cell - gastrin
S cell - secretin
I cell - cholecystokinin
ECL cell - histamine
L cell - glucagon-like peptide (GLP-1 & 2) peptide Y (PYY) oxyntomodulin
K cell - gastric inhibitory polypeptide/GIP
N cell - neurotensin
M? cell - motilin
D cell (antral) - somatostatinCoordinated with extrinsic & intrinsic neural controls and interacting amongst themselves
EC cell - serotonin
A cell - ghrelin
110
EXOCRINE PANCREAS Controls
Duodenum
Exocrine aciniEnteroendocrine cellsSecretin & CCK
digestive enzymes
HCO3- ions
RESPONSE
Acid Fats Peptides
STIMULI
CONTROLLER
+ Vagal cholinergic control
111
SOURCES OF ‘GUT’ HORMONES
RECTUM
LIVER
PANCREAS
GALL BLADDER
STOMACH
SMALL GUT
LARGE GUT
Bile
gastrin ghrelin
Duodenumcholecystokinin motilin
somatostatin
neurotensin
GIP-1
GLP-1&2 Peptide Y
insulin glucagonPPY somatostatin
secretin
Oxyntomodulin
112
SOURCES OF ‘GUT’ HORMONES
PANCREAS
STOMACH
SMALL GUT
LARGE GUT
gastrin ghrelin
Duodenum cholecystokinin motilin
somatostatin
neurotensin
GIP-1
GLP-1&2 Peptide Y
insulin glucagon PPY somatostatin
secretin
Oxyntomodulin
113
Enteroendocrine cell types III
Immunostaining for the peptide or chromogranin and fluorescence methods for the amine derivatives now provide clear identification of the cells, but against a background of the old silver-based cell nomenclature
A messy story*, because of the various staining reactions of enteroendocrine cells (particularly with silver methods) based on the peptide hormones, the associated chromogranin storage protein in the granules, and any catecholamine, serotonin or histamine content.
ECL cell - EnteroChromaffin-Like cell
114
Adipocyte hormones & other metabolic players
RECTUM
LARGE GUTLIVER
SMALL GUT
STOMACH PANCREAS
GALL BLADDER
ES
OP
HA
GU
S
MOUTH
APPENDI X
SALIVARY GLAND
AIRWAY
HYPOTHALAMUS Appetites
Homeostasis Emotion
CEREBRAL CORTEX
Cerebellum
Pons
Mid-brain
Medulla
PITUITARY
TALUS
CALCANEUS Metatarsal
FEMUR
Fat cell
Adipocytes
MUSCLE
115
Adipocyte hormones -
LIVER
HYPOTHALAMUS
TALUS
CALCANEUS Metatarsal
FEMUR
Fat cell
Adipocytes
MUSCLE
LEPTIN
ADIPONECTIN
for energy balance and glucose homeostasis
116
Visceral/abdominal fat & type II diabetes, etc
LIVER
HYPOTHALAMUS
TALUS
CALCANEUS Metatarsal
FEMUR
Fat cell
Adipocytes
MUSCLE
LEPTIN
ADIPONECTIN
MACROPHAGES(Ms)
Macrophages accumulate in the stroma of the fatty tissue, become activated to release abnormal cytokines , e.g., TNF-,that disrupt many metabolic pathways
so that the visceral adipose tissue is permanently inflamed and dangerous, e.g.
Adipocyte production of adiponectin falls
Insulin signalling goes bad, etc.
117
TESTIS & LEYDIG CELLS
Peritubular myoid cells
LEYDIG INTERSTITIAL CELLSAcidophil Much smooth ER Lipid droplets Crystals of Reinke
SERTOLI CELLS
Sperm
layered SPERMATOGENIC CELLS
{
stratified germinal epithelium
BASAL LAMINA
SEMINIFEROUS TUBULE
SEMINIFEROUS TUBULE
118
HORMONESPITUITARY GONADOTROPHS
HYPOTHALAMIC NEURONS
INTERSTITIAL CELLS
SEMINIFEROUS TUBULE
PENIS
SEMINAL VESICLE
PROSTATE
RETE TESTIS
TUBULUS RECTUS EFFERENT
DUCT
EPIDIDYMIS
DUCTUS DEFERNS
BULBOURETHRAL GLAND
urethra
Androgens
Courtship & Coital behaviors
GnRHFSH
LH
1
2 34
5 Secondary sexual characters
67
Somatic growth & metabolism