Hormones of protein nature

BSMU
Department of Biochemistry
Abdullina G.M.
pothalamus is the top of neuroendocrine system which directly
s nervous and endocrine system. Exactly in here nerve impulse is
nverted to a chemical signal
response to stimulatory effects of CNS hypothalamus produces 2
pes of peptides
eleasing factors (liberins) and Inhibitory factors (statins)
hich modulate secretion of the corresponding hormones of hypophysis
y the change of cAMP or IP3 levels in pituitary cells
Hormones of hypothalamus
• Releasing factors (Liberins) Inhibiting factors (Statins)
• Thyrotropin releasing h-n (TRH) Somatostatin
• Corticotropin releasing h-n (CRH) Prolactostatin
• Growth h-n releasing h-n (GHRH) Melanostatin
• Gonadotropin releasing h-n (GnRH)
Prolactin releasing h-n (PRH)
•
Regulation of endocrine system: negative feedback mechanism
ho
Central nervous system

Hypothalamus
_
Liberins + Statins -

Hypophysis
_
Tropic hormones

Endocrine glands
hormones

Target tissues
 ormones of anterior lobe of pituitary (adenohypophysis)
Growth hormone (GH), somatotropin
hyroid stimulation hormone (TSH), thyrotropin is a glycoprotein,
timulating thyroid gland to produce T4-tetraiodithyronine and T3
rolactin (luteotropin) is a 199 AA protein, specific action is to stimulate
actation, in puberty, in pregnancy – enlargement of mammary gland,
ynthesis of lactalbumin, TAG and phospholipids also acts as a cytokine
nd regulates immune system, production of sex hormones, control
arental behavior.
ollicle stimulating hormone (FSH), follitropin, Luteinizing hormone (LH),
utropin are glycoproteins controlling gonads - ovaries and testis
morphogenesis – growth of ovaries and spermatogenesis (FSH) and
ecretion of sex hormones, (LH))
Adrenocorticotropic hormone (ACTH), corticotropin controls secretion
f glucocorticoids by adrenal cortex
Growth hormone is 22kD-prorein (191amino acid
residues) produced in somatotropic cells of pituitary
• Target cells are almost all cells of the body including
• Liver, adipose tissue, muscles, cartilages, brain
• GH Increases the size of the body, length of the bones, the mass of
skeletal muscles and soft tissues
Regulation of Growth hormone secretion

Hypothalamus

- GHRH + somatostatin - +

Adenohypophysis
Growth hormone
-
Liver

IGF-I:insulin like
growth factor
mitogenic effect
growth
• Metabolic effects (mediated by Ca-ions and IP3)
• Hyperglycemic effect: GH inhibits uptake and oxidation of glucose
by tissues, stimulates gluconeogenesis (synthesis of glucose from
non-carbohydrate precursors)
• Lipolitic hormone by stimulation of TAG-hydrolysis and fatty acids
oxidation
• Anabolic effect: GH stimulate protein synthesis in many tissues

• Effect on growth and mitogenic effect is mediated by specific

peptide messengers - IGF (insulin like growth factors) produced by
liver in response to GH-action
• Proliferation of chondrocytes – bone growth
cess and deficiency of
owth hormone –
omegaly, gigantism and
arfism
oopiomelanocortin (POMC) is produced by corticotrophs of pituitary
d split to several peptides -
rmones of POMC- family

POMC
(266 amino acid residues)

ACTH β-Lipotropin
α-MSH 96 AA-s
39 AAs

α,β,γ-
β-MSH endorphins
13 AAs 13-26 AAs
α,β,Υ-MSH (melanocyte stimulating hormones)
timulate production and release of melanin by melanocytes of skin,
hair,(also suppress appetite, control sexual arousal)
Production increases in pregnancy
β –lipotropin is 90 AA peptide with lipid mobilizing function
osterior lobe of hypophysis stores and releases cyclic
onapeptites (9 amino acid residues) – oxytocin and vasopressin
Both peptide hormones are produced by hypothalamus and
transported with the help of protein carriers neurophysins into the
posterior pituitary

xytocin stimulates contraction of smooth muscles of uterine in labor

so stimulates contraction of smooth muscles of mammary glands (milk
ejection)
Vasopressin (antidiuretic hormone, ADH)

• Synthesis depends on osmolality of plasma (secreted when osmotic

pressure increases).
• There are 2 main targets
• 1) epithelial cells of kidney (V2-Receptors, cAMP-messenger system)
where ADH increases reabsorption of water
• 2) vascular smooth muscles (V1-Receptors, IP3-messenger) where
vasopressin stimulates contraction of vascular smooth muscles)
 hanism of ADH action in kidney (by V2 receptors):transduction of ADH signal
es insertion of APQ-2 –aquaporin's (proteins water channels) into the plasma
mbrane ant reabsorption of water and isotonic amount of Na+.
Diabetes insipidus is a condition caused by ADH
deficiency (or resistance)
• Symptom
• Excess urination - polyuria (5-10 liter of solute free-urine of the low
density per day)
•
Mechanism of action of vasopressin (ADH) on the vascular smooth
muscles contraction (by V1 receptors)

• vasopressin

V1 receptor

G S –protein, activation of
phospholipase C
Production of IP3

Release of Ca++

vasoconstriction
Melatonin – hormone of epiphysis(Pineal gland),
regulation of circadian rhythms
Melatonin generation system - 3 features
• 1) photosensitivity (high production in night and darkness)
• 2) synchronization of circadian (diurnal) rhythmicity (sleep wake
timing)
• 3) age related decrease in activity
• 4)antioxidant activity
Thyroid gland hormones
• 1) follicular ells produce iodinated hormones (iodothyronines) –
tetraiodothyronine (T4, thyroxin) and triiodothyronine (T3).
• 2) parafollicular C-cells produce peptide hormone calcitonin
egulation of thyroid system: negative feedback
ontrol
Structure of iodinated hormones of thyroid glands

Thyroxin -
tetraiodothyronine

Triiodothyronine

reverse Triiodothyron
(not active)
 Biosynthesis of thyroid hormones(THs)
urs on the Thyroglobulin - 660kD glycoprotein of the thyroid gland follicle
hyroglobulin:
of 5000 amino acid residues is tyrosine
o 1% - iodine
0% - carbohydrate
ps of biosynthesis
Uptake of iodine ions by thyroid gland: thyroid gland accumulates iodine
h the help of active transport ( symport with sodium ion)/
ily requirement in iodine is150-200 micro g
Activation of iodine by thyroperoxidase
odination and coupling of tyrosine residues of thyroglobulin
Release of T4 (95% of the thyroid gland synthesis) and T3(20%) from
roglobulin by proteolysis into the blood stream
 -
Activation of I (anion iodate) by
thyroid peroxidase

2I - + H2O2 + 2H + → 2I + + 2H2O
nation of tyrosine residues of thyroglobulin and oxidative coupling of iodothyronines
blood T4 is transported with the help of thyroxin-binding protein (α-globulins)
e more active T3(10 times more active than that T4) is formed in target tissues f
by deiodination (deiodinases enzymes are seleno proteins).
ological effects of thyroid hormones:
owth, cell differentiation, metabolism
and T4 act through the intracellular receptor and cytosolic mechanism (by
odulating gene expression).
ects of THs:
ssential for development of fetal and neonatal brain
ncrease the basal metabolic rate (consumption of O2 and heat production) by
mulating de novo synthesis of enzymes involved in cellular respiration
tivate Na,K-ATP-ase
mulate glycolysis and gluconeogenesis (hyperglycemic effect)
mulate lipolysis, both synthesis and oxidation of cholesterol (in hypothyroidism
e blood level of cholesterol increases)
crease amount of protein (anabolic effect), But catabolic in hyperthyroidism
ypothyroidism in adults – Myxedema (retention of water, sluggishness, low body
mperature, decreased basal metabolic rate, hypercholesterolemia)
Hypothyroidism in children – Cretinism (deformities, mental
retardation)
 yperthyroidism ( exophtalmos , tremor, irritability, high body
emperature, negative nitrogen balance
Hormones of adrenal medulla (chromaffin
cells)
• Produces 85% of the total epinephrine and also produces
neurotransmitters dopamine, norepinephrine (catecholamines)
• Synthesis of epinephrine is directly activated by the sympathetic
nervous system (pain, hypoxia, exercise…)
Biosynthesis of catecholamines
Epinephrine is a stress hormone (‘’fight or flight’’ response). The main targets
liver muscles, adipose tissue
ypes of adrenoreceptors
-Rc trigger synthesis of IP3 (mediate regulation of vascular tone)
-Rc trigger synthesis of cAMP (mediate metabolic effects)
ysiologic effects of epinephrine
creases heart rate, cardiac output
laxation of large arteries of lungs, heart, brain
ontraction of the smooth muscles of peripheral arterioles (redistribution of
ood flow in a favor of the life important organs)
etabolic effects
yperglycemic (mobilization of glycogen, inhibition of glucose oxidation)
polytic (mobilization of fatty acids by TAG hydrolysis)
tabolic effect
Hormones of pancreas
• -α cells produce glucagon
• - β cells produce insulin
• -δ cells produce somatostatin (function: it inhibits production of both
insulin and glucagon)
• -γ cells produce pancreatic polypeptide (36-amino acid peptide,
secretion is stimulated by eating, exercising, function: it inhibits gall
bladder contraction and exocrine secretion of pancreas)
Insulin is synthesized from the earlier protein precursor
Insulin
• Synthesis and release of insulin is stimulated by hyperglycemia
• (in lesser degree it is affected by amino acids, fatty acids and Ca-ions)
• Mechanism (how the insulin secretion is affected by the blood glucose
level):
• 1) glucose enters β cells through the GLUT-2 transporters which have
high affinity for glucose
• 2) glucose is oxidized with β cells production ATP
• 3) high ATP closes K+-channels
• 4) accumulation of potassium causes depolarization and opens voltage
regulated Ca++-channels
• 5) increase of calcium in cytoplasm causes the release of insulin from
secretory vesicles
Targets for insulin are all cells of the body but the highest
density of Rc is found in liver, muscle and adipose tissue
• Mechanism of action includes binding to the plasma Rc with the
tyrosine kinase activity
 insulin

Membrane receptor
with tyrosine kinase
activity

IRS-I
phosphorylation

MAPK PI-3K
Mitogen activated Phosphatidyl
Protein kinase inositol -3 kinase

Mitogenic effect Metabolic effects:

Cell proliferation Hypoglycemic
Cell growth Lipogenetic
anabolic
• Hypoglycemic effect
• Insulin signal causes activation of GLUT-4 transporters and uptake of
glucose by skeletal muscles and adipose tissue
• Insulin activates all glucose utilizing pathways (glucose oxidation,
synthesis of glycogen)
• and inhibits glucose producing pathways (glycogen decomposition
and gluconeogenesis)
Glucagon is 29 amino acid peptide released from the
alfa cells in response to hypoglycemia
• Targets are liver and adipose tissue (but not skeletal muscle)
• Effects are opposite to insulin:
• Hyperglycemic
• Lipolytic
• Catabolic
• Glucagon acts on target cells by activating adenylate cyclase and
protein kinases (insulin signal decreases cAMP through the activation
of phosphodiesterase and activates protein phosphatases)