The endocrine system TZs 2020 - Semmelweis Egyetem
Transcript of The endocrine system TZs 2020 - Semmelweis Egyetem
Zsuzsanna Tóth, PhD
Semmelweis University, Dept. of Anatomy, Histology and Embryology
The endocrine system
The role of the autonomic nervous system
Claude Bernard
• „milieu intérieur” concept; every organism lives in its internal environment that is
constant and independent form the external environment
Walter Bradford Cannon
homeostasis;
• an extension of the “milieu interieur” concept
• consistence in an open system requires mechanisms that act to maintain that
consistency
• steady‐state conditions require that any tendency toward change automatically
meets with factors that resist that change
• regulating systems that determine the homeostatic state :
o autonomic nervous system ( sympathetic, parasympathetic, enteral)
o endocrine system
+
++
+‐
Positive feedback
Negative feedbackBody temperature ↑
Body sweets more
Disrupted sleep,increases fatigue
Fatigue: disabled stress coping
Stress, disrupted sleep
feedback
Homeostatic integration within the hypothalamus
Endocrine system
Not all endocrine glands are under hypothalamic control.
Endocrine gland:
• Epithelial origin (except the adrenal medulla)
• No excretory ducts, unlike in the exocrine glands (i. e. salivary gland)
• Lobes, and lobules, separated by connective tissue septa
• Hormone release into the bloodstream
• Special, fenestrated capillary network
The endocrine system
Classic endocrine organs
Pajzsmirigy,mellékpajzsmirigy
Pituitary gland (hypophysis)
Pineal gland
Ovaries
Thyroid and Parathyroid glands
Testicles
Adrenal gland
Pancreas: Islets of
Langerhans
Thyroid and Parathyroid glands
The diffuse endocrine system
Szinte minden szövetben termelődik hormon.
organ example effect
atrium of the heart atrial natriuretic peptide
(ANP)
reduces the extracellular fluid (ECF) volume by increasing renal sodium excretion
enteroendocrine cellsin the gut
Cholecystokinin (CCK) increases production and release of bile from the gallbladder, hunger suppressant
kidney renin blood pressure regulation‐RAS system
liver hepcidin reduces of iron entry into the circulation
skin vitamine D3 increases of intestinal absorption of calcium, magnesium, and phosphate, boosts the immune system
white adipose tissue leptin reduces energy intake in long term
thymus thymosins immunomodulators
Types of the cell‐cell communication
Hormones: • possess biological activity
• are produced by cells
• act by humoral way
• are effective in small concentrations• have slow and long term effects
• bind to specific, high affinity receptors
• 1 type of hormone→ more target tissue
• 1 type of tissue responds to several
types of hormones
• are released rhythmically
The hormones
electric activity
chemical structure example solubility receptor mechanism of action
protein,
polypeptide,
oligopeptide,
amino‐acid derivates
growth hormone (190 AA)
calcitonin (32 AA)
oxytocin (9 AA),
adrenaline, noradrenaline
Soluble in water (hydrophilic) Extracellular (on
the surface of the cell)
Second messengerschanges in enzymatic activitiesgene expressional changes
steroids
amino‐acid derivates
estrogens, testosterone gluco‐and mineralocorticoids
thyroxine, triiodothyronine
Soluble in lipids(hydrophobic)
intracellular(nuclear, cytoplasmatic)
Direct effects on gene expression
• Hormones in the blood are in free (proteins) or conjugated form ( mostly to
albumins i.e. steroids, small molecules)
• Free hormones have biological activities only
Classification of the hormones
Regulation of the hormone production/release
A. Hypothalamus‐pituitary complex (HPC)
B. Qualitative or quantitative changes in the blood
C. Neuronal regulation
• Pineal gland
• Parathyroid gland
• Islets of Langerhans
• Adrenal medulla
• Placenta
Independent from the HPC:
The hypothalamic‐pituitary (hypophyseal) complex – a neuroendocrine system
neuroendocrine system:the nervous sytem (hypothalamus) and the endocrine system that cooperate
Hierarchic structure
The pituitary is connected with the hypothalamus via the infundibulum
The diencephalon:
• thalamus• hypothalamus• subthalamus• epithalamus
The brain (encephalon) :
• Forebrain (prosencephalon)• telencephalon• diencephalon• Middle brain (mesecephalon)• Hind brain (rhombenchephalon)
sagittal
The hypothalamus
• Biological clock
• Thermoregulation
• Energy balance regulation
• Salt and fluid homeostasis
• Autonomic and endocrine center
• Integrative function
Adeno‐ and neurohypophysis are the main parts of the pituitary
• The adenohypophysis is a glandular, the neurohypophysis is a neuronal tissue.
• Neurohypohysis = posterior pituitary: does not produces hormones
• Adenohypophysis = anterior pituitary: produces its own hormones
• Hypophyseal cleft: between the pars intermedia and pars distalis
Neurohypophysis: Adenohypophysis:
stemInfundibular stalk
The adeno‐ and neurohypophysis are both ectodermal, but have different embryological origin
Rathke's pouch is a depression in the roof of the developing mouth (stomodeum)
• Neurohypophysis: neuroectodermal
• Adenohypophysis: ectodermal
Rathke’s stalk
telencephalon?
The hypothalamus contains neurosecretory cells
Only storage, but not hormone production!
Parvocellular partMagnocellular part
Projectory neurons
Neurosecretory cell: releases and produces hormones in response to a neuronal stimulus
The magnocellular neurons in the hypothalamus project to the neurohypophysis
hypothalamic‐neurohypophyseal neurosecretory system
• Fibers of the magnocellular neurons compose the hypothalamic‐hypophyseal tract.
• Magnocellular neurons express vasopressin (ADH) or oxytocin (different cells).
• Oxytocin stimulates uterus contraction, milk ejection, social bonding.
• ADH increases water absorption in the collecting ducts of the kidney nephron.
• central diabetes insipidus (polyuria, polydipsia)
ADH immunohistochemistry, rat hypothalamus coronal section
Paraventricular nucleus
Median eminence
Optic tract
adenohypophysisneurohypophysis
Oxytocin and vasopressin are transported via the axons connected to carrier molecules called neurophysins
Herring bodies:
• large clusters of neurosecretory granules at the terminal portion of the axons
• oxytocin+neurophysin1 or ADH+neurophysin2 is stored in different terminals
• they can be seen at light microscopic level
1. unmyelinited axons
Histology of the pars nervosa
2. special glial cells ‐ pituicytes, oval nucleus3. fenestrated capillaries
1.
2.
3.
pars intermedia
pars nervosa
The hypothalamus contains neurosecretory cells
Only storage, but not hormone production!
Parvocellular partMagnocellular part
Projectory neurons
superior hypophyseal
artery PRIMARY CAPILLARY BED:median eminence, infundibular stalk
portal vessels
portal vessels
Parvocellular cells
SECONDARY CAPILLARY BED: Adenohypophysis
veininferiorhypophyseal artery
Hormone rich bloodvein
vein
tuberoinfundibular tract
Neurohypophysis
Parvocellular neurons project to the median eminence an release hormones into the portal system
Parvocellular neurons of the hypothalamus regulate hormone production of the adenohypophysis:the tuberoinfundibular neurosecretory system
Feedback(long loop)
Feedback (short loop)
Feedback (short loop)
parvocellular nuclei
RHIH
(Ultrashortfeedback loop)
GnRH: gonadotropin releasing hormone or luteinizing‐hormone‐releasing hormone (LHRH)GHRH: growth hormone releasing hormoneSS: somatostatinTRH: thyrotropin‐releasing hormoneDA: dopamineCRH: corticotropin‐releasing hormone or factor (CRF)
Releasing and inhibiting hormones and their targets in theanterior pituitary
testes, ovaries liverfat, cartilage
thyroid adrenal cortex
mammarygland
+ + + +‐ ‐+
Periphery
Diurnal and also episodic (pulsatile) secretion
Acidophils•Somatotrophes produce growth hormone
•Lactotrophes produce prolactin
Basophils
•Thyrotrophes produce thyroid stimulating hormone
•Gonadotrophes produce luteinizing hormone or follicle‐stimulating hormone
•Corticotrophes produce adrenocorticotrophic hormone
Chromophobes
These are cells that have minimal or no hormonal content. Many of the
chromophobes may be acidophils or basophils that have degranulated and
thereby are depleted of hormone. Some chromophobes may also represent stem
cells that have not yet differentiated into hormone‐producing cells.
Pituitary cell types in the adenohypohysis
chromophil
Maurice Tillet, the „French Angel” 1940
overproduction underproduction
During infancy
Pituitary Liver Bone
Muscle
Adipose tissue,lipolysis
‐
‐
‐
+
+
++
++
Hypothalamus
Growth hormone (GH)
During infancy: Gigantism
In adulthood:Acromegaly
‐
v
Prolactin (PRL )
• Regulation by an inhibitory hormone (dopamine)
• Stimulatory: breast feeding, stress
• Prolactinoma is a common type of tumor in the pituitary gland, and it causes infertility
The thyroid gland
Hormones:
1. Thyroxine (T4), triiodothyronin (T3)
2. Calcitonin – regulation of the calcium homeostasis
crycoid cartilage
pyramidal lobe(present in 50%)
right lobe
left lobe
isthmus
The thyroid gland is located in front of the trachea at the level of the larynx in the neck
Frontal view• Moves up and downward during swallowing – medical examination
MICHAEL ROSS/SCIENCE PHOTO LIBRARY
septum
vessels
folliculus
parathyroid gland
thyroid gland
adipose tissue
colloid
Low power microscopic view of thyroid tissue by H&E staining
H&E staining
Folliculi compose the structural units of the thyroid
capsule
follicle(0.2‐1.0 mm)
principal or follicular cell fenestrated
capillary
colloid
parafollicular cell,(C , clear‐cell)
septum
lobule
reticular connective tissue(lymphatic vessels, nerves)
Follicular cell (F) :• simple squamous or cuboidal epithelium• basofil cytoplasm• produces thyroglobulin =colloid• add or substract thyroglobulin into and from
the cavity of the folliculus:‐glycoprotein (~120 tyosine) ‐precursor of thyroid hormones
Parafollicular cell (C):• light or clear cytoplasm• localizes in the epithelium inside the basal
lamina or in groups between the folliculi• produces calcitonin
H&E staining
F
Colloid
Principal (follicular) and C‐cells produce different hormones
Thyroglobulin production and hormone release happens paralelly
MIT: monoiodotyrosineDIT: diiodotyrosine
T4= DIT+DITT3= MIT+DIT
Follicular cavity Follicular cellBlood
thyroid peroxidase +
Functional phases of the follicle
Hypoactive phase: flatter epithelium, big cavity – storage of colloid
Active phase: columnar epithelium, schrinked cavity – little colloid, reuptake
Hormone production is stimulated by, darkness and cold temperature and it is elevated during pregnancy.
Production of T3 and T4 is regulated by the hypothalamic‐pituitary thyroid axis
negative feedback
(‐)
effect
Thyroid
Pituitary
Hypothalamo‐pituitary‐thyroid (HPT ) axis
T3 :•Necessary for the normal development of the central nervous system
• Regulates production of the extracellular matrix components (skin)•Metabolic effects:
increases basal metabolic rateincreases heat production
•Increases the heart rate •Regulates the cholesterol homeostasis•Influences the glucose homeostasis
TSH:•Stimulates T3 and T4 production•Stimulates proliferation of the follicular cells
Over‐ and underfunctioning of the thyroid gland
hypothyreosis = mixodemauntreated treated
cretinismcongenital hypothyreoidism
Basedow diseasehyperthyreosis
Dietary iodine is importantfor the normal function!
Hypo‐ and hypertyroidismboth cause goiter
Parathyroid glands are small, oval‐shaped glands near the posterior aspect of the thyroid gland
• Each gland has its own fibrous capsule
dorsal view
Inferior glands‐
Superior glands‐
Two main cell types are the principal and oxyphil cells
Principal or chief cells:● small, polygonal, central round nuclei, contain secretory granules of parathyroid hormone (PTH) and may contain glycogenOxyphil cells:● larger than chief cell, oval, acidophilic cytoplasm ● no secretory granules, no hormone production
OX
OX
trabeculae
Calcitonin and parathyroid hormone regulate the Ca2+ homeostasis
production thyroid C‐cell parathyroid chief cell
blood Ca2+ level reduces increases
regulation blood Ca2+ level blood Ca2+ level
bone break down reduces increases
Ca2+ reabsorption in the kidney reduces increases
Ca2+ absorbtion in the gut reduces increases (indirectly)
active vitamine‐Dproduction
‐ increases
blood phosphate level (renal reabsorption)
‐ reduces
calcitonin parathyroid hormone (PTH)
Lack of PTH‐tetany, lack of calcitonin‐no symptomps.
The adrenal gland
cortexmedulla
capsule• thick, dense connective tissue
• 90%
• yellowish
• corticosteroids
• mesodermal
• 10%
• brownish‐red• catecholamines:
adrenaline, noradrenaline
• ectodermal‐neural crest
It is located on the upper pole of the kidney.
The cortex is subdivided into three concentric layers
Azan staining
1. Thin outer layer, small cells arranged in rounded clusters or curved columns.
2. Thick middle layer, large cells arranged in two cell thick cords.
3. Thin inner layer, the cells are arranged in a net‐like structure.
1.
2.
3.
Zona glomerulosa cells secrete mineralocorticoids,mainly aldosterone
Glomerulosa cells:
• columnar or pyramidal
• ovoid groups (glomeruli)
• fenestrated capillaries
Aldosterone: • increases Na+, decreases K +
resorption in the distal tubules in kidney
• regulated by angiotensin II, blood K+, Na+concentration, (ACTH)
capsule
zonaglomerulosa
capillaries
septum
arterial plexus (*)
*
zonafasciculata
glomerulus
This zone regulates the fluid and osmotic balance
Zona fasciculata cells secrete glucocorticoids
Fasciculata cells:
• 2 cell‐thick cell cords, separated by sinusoids
• numerous lipid droplets in the cytoplasm‐”foamy”
appearence
Effects of cortisol:
• protects against stress (“stress” hormone)
• increases blood glucose level,
• promotes metabolism of lipids, carbohydates and proteins
• supresses inflammation and the immune system
• inhibits bone formation‐ promotes osteoporosis
• iInfluences memory, and learning
• it is regulated by ACTH
sinuses(septa)
Glucocorticoid: glucose+cortex+steroid• Mainly cortisol in humans
The hypothalamic – pituitary – adrenal (HPA) axis regulates the secretory activity of the zona fasciculata and reticularis
Systematic steroid treatment cannot be stopped suddenly, it can cause schock!
capsule
z. reticularis
z. glomerulosa
z. reticularis
z. fasciculata
aldosterone
cortisol
androgens
depressionheart diseases STRESSZ
ulcerpost traumatic stress disease
skin conditions
cancer
infectious diseases
asthma
(1907 - 1982)
Hans Selye
The stress concept
Stress (1960):
• „non‐specific reaction of the body to stimuli
(stressors) that disturb the steady‐state
condition of the homeostasis and require
adaptation
• Eustress (positive) and distress (negative)
• acute and chronic stress
A Selye féle Általános Adaptációs Szindróma fázisai
• Chronic diseases develop in the resistance stage
• Some stress (cortisol) is needed to the optimal
performance
Yerkes-Dodson’s law
The general adaptation syndrome (GAS)
Zona reticularis cells secrete gonadocorticoids (androgens)
Reticularis cells:
• irregular network of small cells
• ACTH regulated hormone production
The androgens are transformed into
testosterone or estrogen
Androgens:
• are less significant in adults
• are important during embryonic development‐
the function is not known exactly
• in women contribute to the estrogen
production after menopause
• regulate function of the sebaceous glands
Medullary cells secrete adrenaline and noradrenaline
Medullary cells:
• relatively large, round or columnar, basophilic
• neurosecretory cells, modified neurons
• sympathetic innervation
• secretory granules: adrenaline and noradrenaline
production in different cell types
• chromaffin reaction: the hormones are oxidized
by chromate salts resulting brownish color
• adrenaline: stress reaction: Fight or flight
• noradrenaline: vasoconstriction at the periphery
Chromate salt treatment
Cortex
Sympathetic activation:Fight or flight (Cannon’s) reaction
• energy mobilization
• preparation for escape, or fight
• generalized
adrenal
vasoconstriction
vasoconstriction
The gonads: the testis
• Located within the scrotum, surrounded by a connective tissue capsule• Descends from the abdominal cavity during the embryonic development• Lobules‐connective tissue septa• Exocrine (sperm production) and endocrine (testosterone production) organ• Convoluted seminiferous tubules: Sertoli‐cells (“nurse” cells) and developing sperm cells• Continously functions starting from puberty• Spermatogenesis: 64 days• Leydig cells: in the interstitium, testosterone production• Regulated by the HPG axis
Seminiferous tubule
https://mmegias.webs.uvigo.es/02‐english/2‐organos‐a/guiada_o_a_07re‐masculino.php
Factors that affect the spermatogenesis:
• temperature• stress• inflammation (mumps)• ishemia• radioactivity• chemotherapy
+
++
FSH: acts on the Sertoli cells, increases spermatogenesis
LH: acts on the Leydig cells, increases hormone production
Testosterone: promotes development of male reproductive tissues and secondary sexual characteristics
Negative feedback:• inhibin by Sertoli cells• testosterone by Leydig cells
The hypothalamic‐pituitary –gonadal (HPG) axis
The gonads: the ovary
• In the pelvis, bilaterally
• Connective tissue capsule
Parts:
• Cortex: developing follicles
• Medulla: vessels, nerves
Follicular development
• Oocytes are present at birth
• Cyclic function from the puberty till the
menopause
• Regulated by the HPG axis
• follicle: oocyte + follicular cells
• different developmental stages of the follicles
are present simultaneously,
• follicular cells proliferate, liquor accumulates
inside the follicle
• follicular cells: estrogen, inhibin production
• Graafian follicule: ovulation
• after ovulation: corpus luteum –progesterone
release
• corpus luteum degeneration‐menstruation
• pregnancy: the corpus luteum persists for 2
month and produces progesterone
Estrogens:• secondary sexual characteristics• positive feedback on LH before
ovulation• uterine mucosa (endometrium)
proliferation• maintenance of bone density• cardiovascular protection• memory enchancement• menopause!
Progesterone:• endometrium secretory phase• inhibition of uterine contractions• immune system modification• elevation of the body temperature
(ovulation)• inhibition of lactation during
pregnancy
Inhibin: FSH/LH negative feedback
FSH/LH:• promote follicular maturationand hormone secretion of the follicular cellsLH:• LH surge at ovulation• mainanance of the corpus luteum
The menstrual cycle: ovarian and uterine cycles
The placenta
• Fetal and maternal parts (chorion and uterine mucosa)
• Human chorionic gonadotropin (hCG) hormone: promotes the maintenance of the corpus luteum at
the beginning of the pregnancy
• Pregnancy test: detection of HCG at early stage of the pregnancy
• After regression of the corpus luteum the placenta produces:
estrogens and progesterone: prevent abortion, promote proliferation of the uterine tissue
and prepare it for the delivery, prepare the breasts for lactation
The pancreas
endocrine
exocrine
Exocrine secretum: digestive enzymes ‐ leave the pancreas through the ductal system, and get into the duodenum.
Endocrine secretum: hormones ‐ leave the pancreas through the capillaries and get into the circulation.
A cells – glucagon – increases the amount of glucose in blood
B cells – insulin – decreases the amount of glucose in blood
D cells ‐somatostatin – inhibits the other two
F cells – pancreatic polypeptide – stimulates stomach chief cells, inhibits bile and bicarbonate secretion
The islets of Langerhans ‐regulation of the blood glucose level
• Parietal eye (organ): photoreceptive in
reptiles, humans do not have it.
• An anterior evagination of the epiphysis.
• Only few of today’s lizards have it.
• Thermoregulation, reproduction, orientation.
• Parietal nerve:. does not project to the visual
cortex.
The pineal complex: the pineal gland and the parietal eye
The pineal gland produces melatonin
1958: isolation of the hormone from bovine pineal gland extracts.
„mela” (melanin) + „tonin „ (serotonin)
mid‐1960s: the pineal gland is recognized as a component of the endocrine system:
• melatonin is produced in darkness (night)
• adjusts our biological clock to the actual night‐
dark cycle‐regulates the sleep‐wake cycle
• influences the seasonal reproduction in
photosensitive species,
• sympathetic innervation of the gland is needed
to be functional
1917. Feeding extract of the pineal glands of cows lightened tadpole skin.
Histology of the pineal gland
• Pinealocytes‐melatonin production• Glial cells• Mast cells• Connective tissue, septa• Nerve fibers• Capillaries• Brain sand