Download Hormones in intermediary metabolism

Hormones in intermediary
metabolism
Overview of the lecture
• General mechanism of hormone action
• Hormones in intermediary metabolism
– anabolic and catabolic hormones
– insulin and glucagon
– growth hormone
– glucocorticoids
– catecholamines
– thyroid hormones
– testosterone
– leptin
Chemistry of hormones
• Steroids
• Small molecules - NO
• Amino acids derivatives
Receptor
inside the
cell
– thyroid hormones
– catecholamines
• Proteins and peptides
• FA derivates - eicosanoids
Surface
recceptors
Superordinate endocrine gland
Subordinate endocrine gland
HORMONE
Target tissue
EFFECTS
Hormonal signaling system
Suprahypothalamic centers
Hypothalamus
liberins (releasing factors)
statins (inhibiting factors)
Anterior pituitary
Tropins (to the bloodstream)
Endocrine glands
Hormone secretion
Anabolism and catabolism
• Anabolism: synthesis of more complex
substances from simpler precursors,
requires energy (ATP)
• Supply of precursors - from food or from the
degradation of own compounds
• Catabolism: breakdown of complex
compounds into simpler, energy gain (ATP)
• Mobilization of energy reserves
Anabolic and catabolic
hormones
• Anabolic hormones: insulin, growth
hormone, testosterone, ...
• Catabolic hormones: glucagon,
glucocorticoids, catecholamines, ...
Remebrer forever!
Insulin actions
• Increased ratio I / G – switch of
metabolism in the fed state
• Anabolic and lipogenic, lowers glycemia
• Increases storage of glucose and reduces
its production (mainly in the liver – activates
synthesis of glycogen, glycolysis and
PDH, blocks gluconeogenesis)
• Increases the number of GLUT-4 channels in
adipose tissue, skeletal muscle and heart
Insulin actions
• Use of an excess of glucose:
1) energy production
2) synthesis of glycogen
3) synthesis of TAG in liver and
adipose tissue
Insulin actions
• The excessive intake of saccharides can
overload glycogen stores – conversion of
glucose to FA in liver – TAG transport to
adipose tissue
• Activation of lipoprotein lipase
• Inhibits extrahepatic lipolysis (HSL) and
ketogenesis
• Basal insulin secretion hinder excessive
lipolysis and production of ketone bodies
Insulin actions
• Proteoanabolic hormone
• Increases the storage of AA and
proteosynthesis
• Promotes growth
• Promotes K transition into cells
+
Insulin actions
• Fast (seconds)
– increases transport of glucose, amino acids
and K+ into cells
• Medium (minutes)
– stimulation of protein synthesis, inhibition of
protein degradation
– activation of glycogen synthase
• Late (hours)
– increased expression of enzymes
Glucagon actions
• Actions (via cAMP) mainly antagonize those
of insulin – decrease of I/G ratio
• Maintains normoglycemia between meals and
during increased glucose consumption to
ensure a constant energy supply:
• 1) glycogenolysis (in liver)
• 2) gluconeogenesis from lactate, AA (protein
catabolism) and glycerol (lipolysis)
• Inhibition of synthesis of FA and TAG
Growth hormone actions
• Important for growth in childhood, regulates
intermediary metabolism in adulthood
• Direct and indirect (via IGF-1) effects:
– promotes lipolysis
– hyperglycaemic (inhibits glycolysis, increases
gluconeogenesis and glycogen synthesis) – DM
– proteoanabolic (↑ AA transport and protein synthesis)
• Mobilizes energy reserves (starvation, stress) preferably broken down fats, while saving
proteins
Regulation of growth hormone
production
• Pulse secretion, reduced in old age
• Somatostatin and somatoliberin (GHRF)
• Stimulation: maximal secretion in the morning
– stress, hunger, hypoglycemia, decrease of
plasma FA
– first 2 hours of sleep, non REM sleep
• Inhibition:
– high concentrations of IGF (somatomedins)
– REM sleep
Normální
Hypopituarizmus
Glucocorticoids actions - cortisol
• Provide enough E (Glc) to vital organs
(CNS) - required for adaptation to stress
• Increases release of glucose by liver
(stimulation of gluconeogenesis) and
decreases its utilization in the periphery
(excessive action – hyperglycemia and
glycosuria – steroid DM)
• Stimulation of AA release from muscle,
reduction of protein synthesis
• Increases lipolysis, FA level and their use
Regulation of cortisol production
• Pulse secretion (influence of ACTH)
• Dependence on circadian rhythm – peak
in the early morning hours
• 10 times higher during stress
Glucocorticoids actions - cortisol
• Anti-inflammatory – reduces acute
and chronic phase of inflammation,
blocks the release of arachidonic acid
from phospholipids by PLA2
• Immunosuppressive – high doses
e.g. block antibodies production
• Mineralocorticoid – electrolyte and
water balance
Glukokortikoidy - kortizol
Catecholamines actions
• Mobilization of energy reserves and increase
of energy expenditure (uncoupling proteins)
• Increase of hepatic glycogenolysis and
gluconeogenesis – α1 and β2 rec. (mild
glycogenolysis in muscle – β2 rec., main activator is
influx of Ca2+) decrease of glycolysis in liver
• Lipolysis (HSL activation) – β3 rec.
• Protein catabolism
• ↓ insulin secretion – α2 rec. (x β2 r. increases )
α1 receptors
α2, β receptors
Thyroid hormones
• Regulation of synthesis and
secretion: TSH from the anterior
pituitary (feedback regulation)
• T3 is more efficient than T4
(peripheral deiodinase)
Thyroid hormones actions
• Increase in basal metabolic rate - increased
O2 consumption, increased expression of
uncoupling proteins – thermogenesis, increasing
the number and size of mitochondria
• Long-term "metabolic tune" (body's response
during the days and weeks)
• Increased number of adrenergic receptors enhancing effects of catecholamines
• Enhance the expression of growth hormone
Thyroid hormones actions
• ↑ absorption of saccharides in intestine
• ↓ glycogen store
• Stimulation of glucose utilization in the
periphery
• Hyperglycemia (Gothic glycemic curve)
• ↑ lipolysis
• ↓ lipids and cholesterol in the blood (↓
cholesterol synthesis and ↑ secretion of bile)
Thyroid hormones actions
• ↑ protein synthesis, but ↑↑ protein catabolism –
result is proteocatabolic
• Increased breakdown of muscle proteins
• Stimulation of synthesis: Na+/K+ pump,
respiratory chain enzymes, ...
• The pro-growth importance: T3 and T4
support metabolism, which is necessary for
protein synthesis and thus for the influence of
other growth-promoting hormones: STH,
insulin, ...
Testosterone actions
• More potent dihydrotestosterone
(5α-reductase)
• Increases basal metabolic rate
• Increases protein synthesis
• Estrogens have similar effects
(increased protein synthesis)
Leptin actions
• Leptos (thin)
• Peptide hormone secreted by adipose
tissue to an extent proportional to its
amount
• Control of long-term energy homeostasis
• Increased fat stores → more leptin → ↓
food intake (hypothalamus) and increased
resting energy expenditure