Download Endocrine system

2017.03.01.
Endocrine system
Hormones influence their target cells to respond in a specific
way, to the benefit of the organism. It is part of the homeostatic
response to an altered environment, whether external or internal.
1902 Secretin
William Bayliss
(1860-1924)
Ernest Starling
(1866-1927)
„Chemical transmission” of information (almost all cells)
eg. adenosin
local vasodilatation
1
2017.03.01.
Signal transduction
ENDOCRINE
Macrophage
Effector
cell
Effector
cell
PARACRINE
T-helper
Synapse
B-lymphocyte
AUTOCRINE
T-helper
+ intracrine effect
Endocrine system
Immune system
Nervous system
Functions regulated by hormones:
Metabolism
Adaptation to the environment (eg. stress)
Sexual functions
Growth
2
2017.03.01.
„Classic” endocrine
glands
Anterior lobe of the pituitary gland
(Adenohypophysis)
„Diffuse” endocrine
system
Central nervous system
(Hypothalamus)
Thyroid gland
Parathyroid glands
Parafollicular cells of the
thyroid gland
Thymus
Lung epithelial cells
Adrenal cortex
Atrium of the heart
Pancreas
(Langerhans islets)
Kidney
Gastrointestinal tract
Fat tissue
+ placenta
Ovaries
Tissue hormones:
prostaglandins, NO
Testes
Chemical composition of hormones
1) Polypeptide and protein hormones (Glykoproteins)
most hormones
2) Steroid hormones
adrenal cortex, gonads, placenta, calcitriol
3) Amino acid (tyrosine)-derived hormones
Catecholamines (adrenaline, noradrenaline, dopamine)
Thyroid hormones (thyroxine, triiodothyronine)
Solubility of hormones
Water-soluble hormones: Polypeptide and protein hormones, catecholamines
Lipid-soluble hormones: Steroid hormones, thyroid hormones
Solubility of hormones determines their biological characteristics.
3
2017.03.01.
Biosynthesis of peptide hormones
DNA
nucleus
Endoplasmic
reticulum
Preprohormone
ribosomes
cisterns
Prohormone
Golgi
apparatus
Granulum
Hormone
Membrane
C-peptide
A-chain
B-chain
Insulin is released along with equimolar amounts of C-peptide. Concentration of
C-peptide can be measured in the plasma. Its level provides an index of B cell
function in patients receiving exogenous insulin.
4
2017.03.01.
Biosynthesis of steroid hormones
plasma LDL
synthesis
Cholesterol
17,20-lyase
17-OH-ase
Desmolase
Pregnenolone
17-HSDH
Androstanedione
17-OH-pregnenolone
3-HSDH
Progesterone
17-OH-progesterone
21-OH-ase
Androstenedione
Testosterone
aromatase
11-deoxycorticosterone
Estrone
11-deoxycortisol
Estradiol
11-OH-ase
Corticosterone
Cortisol
18-OH-ase
18-OH-costicosterone
Synthesis:
Smooth endoplasmic reticulum
Mitochondria
18-HSDH
Aldosterone
Enzymes:
Cytochrome P450
Hydroxysteroid dehydrogenases
DHEAS = Dehydroepiandrosterone sulfate
Cholesterol
C21
Progesterone
C19
Aldosterone
Cortisol
C18
Testosterone
Estradiol
5
2017.03.01.
Sekretion of hormones
Polypeptide and protein hormones, catecholamines:
They are stored in vesicles, exocytosis results in expulsion of vesicle contents.
Lipophilic hormones:
They are synthesised on demand. Their release into the bloodstream is the
consequence of the passive diffusion through the lipid membrane.
Cholesterol can be esterified and stored intracellularly in lipid droplets.
Thyroid hormones are stored in colloid.
Rhythm of hormone secretion
Hours
ovulation
Weeks
Estradiol
Estradiol
minutes
menstruation
Minutes
days
Lifespan
hours
Circadian rhythm
sleep
years
24 hours
6
2017.03.01.
The half-life of a hormone in blood is
defined as that periode of time needed
for its concentration to be reduced by
half.
Hormone concentrations in the
blood: unstable! 10-9 – 10-12 mol/l
It depends on the rate of production,
secretion and degradation.
Measurement:
(Bioassay)
Galli-Mainini pregnancy test
Radioimmunoassay (RIA)
Enzyme-linked immunosorbent assay (ELISA)
antibody
antigen
labeled antigen
komplex
7
2017.03.01.
Activation of hormones in peripheral tissues
Thyroid hormones: Thyroxine
Androgens: Testosterone
Triiodothyronine
Dihydrotestosterone
Transport of hormones in the circulation
Water-soluble hormones: generally in a free form
Lipid-soluble hormones: free + protein-bound form
Transportproteins: prealbumin, albumin, globulins
Only free hormones are biologically active, but bound and free fractions are
in equilibrium.
Breakdown of hormones
Liver, kidney (proteolysis of peptide hormones)
Liver (steroid hormones - reduction or conjugation with glucuronic acid)
Effects of hormones on target cells
Hormone receptor
1 hormone – more receptors (ADH – V1,V2)
1 receptor - more hormones
Autoantibodies (Basedow/Graves disease)
8
2017.03.01.
Action – hormone receptors – intracellular signal transduction
Hormone receptors:
1) Membranreceptors (Peptid- und Proteinhormone)
- extracellular domain
- membrane-spanning section
- intracellular domain
G protein coupled receptors
Guanylate cyclasecoupled receptor
Tyrosin kinase
receptor
Tyrosin kinasecoupled receptor
2) Intracellular receptors of lipid-soluble hormones:
+ membrane receptors
Typ I: in the cytoplasm (glucocorticoids, mineralocorticoids, androgens, progesterone)
Typ II: in the nucleus (thyroid hormones, calcitriol, estrogen)
9
2017.03.01.
Axis of the hypothalamus/adenohypophysis/hormone-secreting
gland (negative feedback regulation)
HYPOTHALAMUS
ADENOHYPOPHYSIS
„long loop”
feedback
„short loop”
feedback
HORMONE
SECRETING
GLAND
Hormone
Metabolites
TARGET CELL
metabolic
effect
Positive feedback regulation
Estradiol
Estradiol
menstruation
Ovulation
days
10
2017.03.01.
Neural control of endocrine functions
Autonomic innervation:
- direct
- regulation of blood flow
Neural activity of the oxytocin secreting neurons
Neurosecretion:
hypothalamus, adrenal medulla
Increase in pressure in the ducts
Permissive effect:
eg. requirement of glucocorticoids to be present for catecholamins to exert their effects.
Pathophysiology of hormone secretion
Hypofunction
Hormone or receptor ?
Hyperfunction
- tumour
- stimulating autoantibodies
- disturbances of feedback regulation
Hormone therapy
Hormone replacement
Treatment
Glucocorticoids: anti-inflammatory and immunosuppressive agents
Estrogens, gestagens: hormonal contraception
Doping (growth hormone, androgens) side effects!
11
2017.03.01.
Hypothalamo-hypophyseal system
Hypothalamus
Hypophysis (Pituitary gland)
Magnocellular neurons
Parvocellular neurons
Paraventricular nucleus
Supraoptic nucleus
Adenohypophysis
Neurohypophysis
limbic system
circumventricular
organs
autonomic
function
third ventricle
portal vessels
Adenohypophysis
Releasing hormons
Inhibiting hormons
Neurohypophysis
GH,
12
2017.03.01.
Neuropeptides secreted by the Hypothalamus
1. Supraoptic and Paraventricular nuclei (Magnocellular neurons):
Vasopressin (Antidiuretic hormone - ADH)
Oxytocin
2. Hypophysiotropic releasing and inhibiting hormones (Parvocellular
neurons):
Corticotropin-releasing hormone CRH
Growth hormone-releasing hormone GHRH
Gonadotropin-releasing hormone GnRH
Thyrotropin-releasing hormone TRH
Growth hormone-inhibiting hormone (Somatostatin)
Prolactin-inhibiting hormone (Dopamine!)
3. Other neuropeptides:
Enkephalin, Endorphin, Substance P, Calcitonin-gene related
peptide etc.
Hormones of the adenohypophysis
1) Hormones acting on endocrine glands
Adrenocorticotropic hormone (ACTH)
Thyroid-stimulating hormone (TSH)
Gonadotropins: Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
2) Hormones acting on peripheral tissues
Growth hormone (GH)
Prolactin (PRL)
LH/FSH
TSH
40%
ACTH
25%
GH
PRL
13
2017.03.01.
Prolactin
Gonadotropins
Prolactin
Gonads
Adrenal
Growth
hormone
Growth
hormone
Thyroid gland
cortex
Hormones acting on endocrine glands
Hormon
Abbreviation
Chemical nature
Effect
Adrenocorticotropic
hormone
ACTH
Polypeptide
Stimulates secretion and
growth of the adrenal cortex
Thyroid-stimulating
Hormone
TSH
Glykoprotein
Stimulates thyroid secretion
and growth of thyroid gland
Follicle-stimulating
Hormone
Luteinizing
Hormone
FSH
LH
Glykoprotein
Glykoprotein
Stimulates ovarian follicle
growth in female and
spermatogenesis in male
Stimulates ovulation and
luteinization of ovarian follicles
in female and
testosterone secretion in male
14
2017.03.01.
1. Pre-pro-opiomelanocortin (POMC)
Signal peptide
N-terminal
fragment
β-lipotropin
γ-lipotropin β-endorphin
ACTH - Adrenocorticotropic hormone
MSH - Melanocyte-stimulating hormone
2. Glykoproteins: TSH, FSH, LH
carbohydrate
3. Somatomammotropic hormones
Growth hormone
Prolactin
191 amino acids
199 amino acids
15
2017.03.01.
Feedback control
TRH-TSH-Thyroid gland
CRH-ACTH-Adrenal cortex
GnRH-FSH/LH-Gonads
16