Endocrine system
Intercellular communication
Synaptic
Autocrine
Paracrine
Endocrine
Neurocrine
Blood
Blood
Tissue
Synapsis
Distant
Local
Contact
• Endocrine organs (e.g. pituitary, thyroid, parathyroid, adrenal)
• Endocrine tissue within other organs
(pancreas, gonads, kidneys, placenta)
• Isolated endocrine cells (DNES, APUD)
• Neuroendocrine cells
General properties of endocrine organs
• Common developmental scheme
- invagination of epithelia, losing contact with the original tissue
- ducts absents
• c.t. capsule + septs
• Trabecules of glandular epithelium, follicles or clusters of glandular
cells
or
• Neurosecretory cells
• Capillary network
- Fenestrated capillaries
- Sinusoids
General properties of endocrine organs
• Merocrine secretion
- not only hormones – endocrine gland is sensu lato also liver
• steroids – hydrophobic, intracytoplasmic or nuclear receptors (sex
hormones, corticoids)
• proteins and polypeptides – hydrophilic, plasma membrane
receptors (insulin, pituitary hormones, PTH, …)
• aminoacids and their derivatives (adrenalin, noradrenalin, thyroxin)
General properties of hormones
v
Pituitary gland (gl. pituitaria)
• sphenoid bone
• sella turcica
• fossa hypophysialis
Pituitary gland (gl. pituitaria)
Pituitary gland (gl. pituitaria)
• adenohypophysis (pars distalis, pars tuberalis, pars intermedia)
• neurohypophysis (pars nervosa)
• infundibulum, eminentia mediana
Pituitary gland (gl. pituitaria)
• adenohypophysis - glandotropic hormones, prolactin, GH
• neurohypophysis - hypothalamic hormones - ADH, oxytocin
• anatomical and functional association with hypothalamus
• capillary systems and neuroendocrine secretion
Pituitary gland (gl. pituitaria)
Hypothalamus
• small region of diencephalon
• complex neuroarchitecture
• core of the limbic system
• complex functions
- regulation of temperature, emotions,
eating behavior, circadian rythms
- hormonal regulation controlled by
various stimuli (osmoreception,
concentration of nutrients,
electrolytes, systemic functions - pain)
• hypothalamic nuclei
- n. supraopticus, n. paraventricularis
- magnocelullar neurons - tractus
hypothalamo-hypophysialis
- parvocelullar neurons - capillaries in
eminentia mediana
CC
NC
Th PuGP
Hyp
SI
Hypothalamo-hypophyseal system
ncl. paraventricularis
ncl. supraopticus
Tractus hypothalamo-hypophysialis
hypophyseal arteries
posterior lobe
secondary plexus of anterior lobe
Capillary system of hypophysis
Embryonal development of pituitary gl.
• Ectoderm (Rathke’s pouch)
• Neuroectoderm of ventral wall of diencephalon
Embryonal development of pituitary gl.
A = fossa
B = hypothalamus
C = eminentia mediana
D = adenohypophysis
Adenohypophysis (anterior lobe)
Chromophilic cells
Acidophils
- Somatotropic (STH, somatotropin), 50%
- Mammotropic (LTH, prolactin), 10-25%
Bazophils
- Thyrotropic (TSH), 3-5%
- Gonadotropic (FSH, LH), 10-15%
- Corticotropic (POMC, ACTH, MSH), 15-25%
Chromophobic cells
• undifferentiated cells
• degranulated (“empty“) chromophils
• stromal cells
Nonglandotropic
- direct effect on target tissues
Glandotropic
- regulation of other endocrine glands
Adenohypophysis (anterior lobe)
Adenohypophysis (anterior lobe)
”FLAT PEG”
• FSH
• LH
• ACTH
• TSH
• Prolactin
• Endorphins
• Growth hormone
Pro-opio-melanocortin (POMC)
rough ER → pre-prohormon
produced by various tissues
cleavage to
• ACTH (target: adrenal cortex → kortisol)
• MSH (target: melanocytes - mostly in paracrine way)
• lipotropin (lipolysis, steroidogenesis)
• endorphins
FSH (folitropin), LH (lutropin)
• gonadotropic cells of adenohypophysis stimulated by GnRH
• glycoproteins, 30kDa
• heterodimer, two noncovalent bound subunits (a/ - common for - LH, FSH, TSH,
hCG, b/ - specific)
• FSH receptor (testes, ovarium, uterus) G-protein coupled receptor
- glycosylated extracellular domain of 11 leucine rich repeats specific to FSH
- after ligand binding, activation of G-protein and cAMP signaling
- alternative activation of MAPK cascade (ERK)
- complex signaling response (prostaglandins, PLPc, NO)
FSH LH
ovarium follicle development (FSHR in m. granulosa
cells)
ovulation, development of
corpus luteum, production of
androgens in thecal cells
testes spermatogenesis, FSHR in Sertoli cells production of testosterone in
Leydig cells (expression of LHR)
extragonadal FSHR in secretory endometrium of luteal phase
uterus (endometrial functions, embryoendometrial
interactions)
uterus, seminal vesicles,
prostate, skin... unknown
function
TSH, thyrotropin
• thyrotropic cells of adenohypophysis stimulated by TRH
• production of T4 (thyroxin) a T3 (triiodothyronin) by thyroid gland
• glycoprotein, 28,5 kDa, heterodimer, two noncovalent bound subunits (a, b)
• TSH receptor on thyroid follicular cells
• G-protein signaling → adenylylcyklase → cAMP
- cAMP → iodide channels (pendrin), transcription of thyreoglobulin, endo- and
exocytic pathway
• cross-reactivity with hCG → in pregnancy - alterations in synthesis of thyroid
hormones (gestational hyperthyroidism)
GH, somatotropin, growth hormone
• somatotropic cells of adenohypophysis stimulated by GHRH (somatocrinin)
• several molecular isoforms (alternative splicing), ~20-24 kDa
• broad spectrum of target cell types and physiological circuits
- transcription of DNA, translation of RNA, proteosynthesis
- lipid use (fatty acid mobilization, conversion to acetyl-CoA)
- inhibition of direct use of glucose, stimulation of glukoneogenesis
- transmembrane transport of aminoacids
- proteosynthesis in chondrocytes and osteoblasts, proliferation, osteogenesis
• GHR in various tissues
- RTK, JAK-STAT
• somatomedins
- small proteins (MW 7,5 kDa), IGF-like
- produced by liver
• various pathologies associated with GH
Clinical links
Hypophyseal tumors
• compression of surrounding structures
(optic chiasma)
• hyperfunction of endocrine component
- prolactinoma - galactorrhea
- hypogonadism (alterations of GnRH)
- gigantism - acromegaly
- nanism
Posterior hypophysis (neurohypohysis)
nonmyelinated nerve fibers
– axons of neurosecretory cells (c.a.
100 000) of hypothalamic nuclei (n.
supraopticus and paraventricularis)
pituicytes (neuroglia)
- astrocyte-like (intermediate
fialmets, GFAP)
- local control of secretion from
neuroscretory termini
- Herring bodies – neurosecretory
endings – dilatation close to
capillaries
Hormones
- oxytocin (OT)
- antidiuretic hormone (ADH,
vasopresin)
Oxytocin
• nonapeptide
• magno-cellular supraoptic and paraventricular nuclei of the
hypothalamus
• OR - G-coupled receptor
• lactation reflex
• uterine contraction
• social behavior
Vasopressin
• nonapeptide
• retention of water
• effective in collecting duct and distal
convoluted tubule (aquaporine
translocations)
• blood pressure regulation by affecting t.
media
• diabetes insipidus, hypernatremia,
polyuremia
Anatomy Microscopic anatomy Hormones and target tissues
Anteriorlobe(adenohypophysis)
pars distalis
superior
hypophyseal
arteries →
primary
capillary plexus
→ hypophyseal
portal veins +
inferior
hypophyseal
arteries
→
secondary
capillary plexus
→ hypophyseal
portal veins →
vv. jugulares
internae
trabecular epithelium in cords and clusters,
reticular fibers
chromophobes
undifferentiated cells
degranulated chromophilic cells
stromal cells
lack hormonal activity
chromophils
acidophilic
nonglandotropic
mammotropic
cells
smallpolypeptides
dopamin (PIH)
⊥
(PRF → prolactin
mammary gland in
gravidity and
lactations
somatotropic
cells
somatostatin (GHIH)
⊥
GHRH → somatotropin
(STH)
directly liver and
growth plates
other tissues via
somatomedins
basophilic
glandotropic
corticotropic
cells
glycoproteins
CRH → ACTH, MSH
adrenal cortex
→ cortisol
melanocytespars tuberalis
thyrotropic cells TRH → TSH
thyroid
→ thyroxin, T3
pars intermedia
Rathke’s cysts
gonadotropic
cells
GnRH → FSH (ICSH), LH
gonads
→ androgens,
estrogens,
progesterone
Posteriorlobe
(neurohypophysis)
eminentia
mediana →
infundibulum
anterior and
posterior
superior
hypophyseal
arteries →
primary
capillary plexus,
fenestrated
capillaries
nonmyelinated axons
of hypothalamic neurons n. supraopticus,
n. paraventricularis (tractus
hypothalamohypophysialis),
pituicytes
smallpeptides
ADH
tubulus reuniens,
ductus colligens
t.media of vessels
oxytocin
myometrium of
uterus during
gravidity
myoepithelium of
lactating
mammary gland
pars nervosa
Epiphysis (c. pineale)
• epithalamus
• c.t. capsule continuous to pia mater
• thin c.t. septa
• nonmyelinated nerve fibers
• pinealocytes (95%, large, pale, round nuclei)
• interstitial neuroglia (astrocytes, dark,
elongated nuclei)
• acervulus cerebri
• melatonin
• pinealocytes
- star-like, modified neurons in trabecules
- association with fenestrated capillaries
- neurosecretory dilatations
- nonvisual photoreception
Epiphysis (c. pineale)
Embryonic development of
epiphysis (c. pineale)
• thickening of caudal part of
ependyma that does not
contribute to development of
choroid plexus at the roof of
diencephalon
• neuroectoderm
Thyroid gland (gl. thyroidea)
• Follicular cells → thyroid hormones (T3, T4)
• C cells → calcitonin
C.t. capsule, septs
Lobes → lobuli - follicles
Follicles (50 µm -1 mm)
- separated by interstitial loose collagen c.t.
- simple epithelium (flat to cubic, according to
secretory activity)
- colloid
Capillary network from thyroid arteries
Thyroid gland - follicles
Thyroid gland - follicles
Follicular cells and C-cells (parafollicular)
C-cells
Synthesis of T3 and T4
T3 synthesis from T4
• T4 half-life in blood 6.5 days, T3 2.5 (T4 is a reservoir for T3)
• deiodination by tissue specific deiodinase enzymes generates T3
T4 synthesis in thyroid
• sodium-iodide symporter transports two Na+ and one I- across the basement
• I− is moved across the apical membrane into the colloid of the follicle.
• thyroperoxidase oxidises 2 I− → I2.
• thyroperoxidase iodinates the tyrosyl residues of thyroglobulin
• (TSH) stimulates the endocytosis of the colloidal content
• endocytic vesicles + lysosomes, lysosomal enzymes cleave T4 from the
iodinated thyroglobulin
• exocytosis
thyreoglobulin
triiodothyronin T3
tetraiodothyronin (thyroxin) T4
C-cells of thyroid
Calcitonin
- inhibition of osteoclasts
Neuroendocrine cells
- pale staining
- epithelial basis, under basal
lamina no contact with colloid
- derived from neural crest
- associate with ultimobranchial
body, (derivative of the
4th pharyngeal pouch)
• endodermal proliferation of pharyngeal floor
• hypobranchial eminence and foramen caecum
• bilobed civerticulum
• ductus thyreoglossus
Thyroid development
Parathyroid gland (gl. parathyreoidea)
6 mm, 130 mg
c.t. capsule and septs
Capillary network
Cords and clusters of glandular cells
- Chief
- Oxyphilic
- Adipose
• Chief
- most abundant
- small cells (7-10µm, big nucleus
- mildly acidophilic
- PTH – calcium metabolism
• Oxyphylic
- large, polyhedral,
- strongly acidophilic
- round nucleus
- glycogen
Parathyroid gland (gl. parathyreoidea)
Parathyroid gland (gl. parathyreoidea)
Parathyroid hormone (PTH,
parathormone, parathyrin)
• 84 aminoacids
• stimulates resorption by osteoclasts
• enhances resorption of calcium and magnesium in
distal tubules and thick ascending limb
• enhances absorption in the intestine (via vD3)
PTH vs. calcitonin
• glandulae parathyroideae superiores from endoderm of 4th pharyngeal pouch
• glandulae parathyroideae inferiores from dorsal process of 3th pharyngeal pouch
- together with thymus descend to lower poles of thyroid
• ectopic PTH gland in thymus or mediastinum
Embryonic development of
parathyroid gland
Embryonic development of
parathyroid gland
c.t. capsule, septs
capillary plexus
Adrenal gland (corpus suprarenale)
Adrenal development
cortex
- mesoderm
- mesothelium, coelomic epithelium
medulla
- neural crest
Adrenal cortex
Adrenal cortex
• Zona glomerulosa (1/10)
- thin layer under capsule
- relatively small cells in coiled glomeruli
- not abundand lipid droplets
- mineralocorticoids
• Zona fasciculata (6/10)
- radially arranged trabecules
- lipid droplets in cytoplasm
- glucocorticoids
• Zona reticularis (3/10)
- branched trabecules
- small, acidophilic cells
- lipofuscin
- androgen precursors
Adrenal cortex hormones
• Steroids produced incortex = CORTICOSTEROIDS
• Steroidogenic cells
- SER, lipid droplets, mitochondria
- mineralocorticoids
- glucocorticoids
• Aldosteron – zona glomerulosa
• Cortisol – zona fasciculata
• Androgens, estrogens, progesteron – zona reticularis
Adrenal cortex
hormones
Clusters of glandular cells in reticular c.t.
- chromaffin cells – modified postganglionic neurons
- ganglionic cells
- capillaries, venules, nerve fibers
- adrenaline and noradrenaline
Neural crest origin
Adrenal medulla
Adrenal cortex
ACTH
Cortisol
- glycogen lysis
- stabilization of glucose levels
- suppression of immune system
Pituitary gland
Adrenal medulla
Adrenaline
- blood pressure,
vasoconstriction, heart rate…
Fight or FlightChronic stress
STRESSHypothalamus
CNS
(sympaticus)
Thank you for attention
Questions and comments:
pvanhara@med.muni.cz