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Introduction to Endocrinology
Prof. dr. Zoran Valić
Department of Physiology
University of Split School of Medicine
Coordination of Body Functions
1) nervous system (neurotransmitters into the synaptic junctions – locally)
2) endocrine system (hormones into blood)3) neuroendocrine (neurohormones into
blood)4) paracrines (secreted into extracellular fluid
and affect neighboring different target cells)5) autocrines (affect same cells)6) cytokines (peptides - 5,4 or 2 - interleukins,
lymphokines, adipokines (leptin))
some endocrine hormones affect many different types of cells of the body (growth hormone, thyroxine)
other hormones affect mainly specific target tissues (ACTH – adrenal cortex)
regulation: metabolism, growth and development, water and electrolyte balance, reproduction, and behavior
Chemical Structure and Synthesis
1) proteins and polypeptides
2) steroids
3) derivatives of the amino acid tyrosine (thyroid and the adrenal medullae)
there are no known polysaccharides or nucleic acid hormones
1) Protein Hormones
widespread, water soluble from 3 (TRH) to 200 amino acids (growth
hormone and prolactin) more than100 amino acids – proteins synthesized on the rough end of the ER preprohormones – prohormones (ER) –
hormones (Golgi apparatus & secretory vesicles) – exocytosis (Ca, cAMP)
2) Steroid Hormones
usually synthesized from cholesterol are not stored lipid soluble most of cholesterol comes from plasma, but
there is also de novo synthesis consist of three cyclohexyl rings and one
cyclopentyl ring combined into a single structure
3) Amine Hormones
derived from tyrosine most of the thyroid hormones combine with
plasma proteins 4x more epinephrine than norepinephrine taken up into preformed vesicles and stored
until secreted (exocytosis) in the plasma in free form or in conjugation
with other substances
Hormone Secretion
some hormones (epinephrine) are secreted within seconds after stimulation, and develop action within seconds to minutes
thyroxine or growth hormone may require months for full effect
concentrations of hormones are incredibly small (from 10-12 to 10-6g/ml) – rates of secretion are extremely small (μg-mg/day)
Control of Hormone Secretion
in most instances – negative feedback mechanisms
controlled variable is sometimes not the secretory rate of the hormone itself but the degree of activity of the target tissue
regulation of gene transcription and translation steps involved in the synthesis of hormones and steps involved in processing hormones or releasing stored hormones
positive feedback – LH, oxytocin cyclical variations – seasonal changes,
various stages of development and aging, the diurnal (daily) cycle, and sleep
Transport of Hormones in Blood
water-soluble hormones (peptides and catecholamines) – dissolved in the plasma
steroid and thyroid hormones – circulate in the blood mainly bound to plasma proteins (usually less than 10% free in solution), biologically inactive (serve as reservoirs, greatly slows their clearance from the plasma)
Clearance of Hormones from Blood
concentration of a hormone in the blood:
1) rate of hormone secretion into the blood
2) rate of removal of the hormone from the blood (metabolic clearance rate – number of milliliters of plasma cleared of the hormone per minute)
one measures : the rate of disappearance of hormone from the plasma & concentration
1) metabolic destruction by the tissues2) binding with the tissues3) excretion by the liver into the bile4) excretion by the kidneys into the urine liver damage excessively high
concentration of steroid hormones half-life of angiotensin II < 1 minute,
thyroid hormones 1-6 days
Hormone Receptors and Their Activation binding to specific receptors at the target
cell – first step of a hormone's action initiation of a cascade of reactions in the
cell – amplification of the effect hormonal receptors are large proteins, each
cell usually has some 2000 to 100,000 receptors
receptor is highly specific for a single hormone
1) in or on the surface of the cell membrane (protein, and catecholamine hormones)
2) in the cell cytoplasm (steroid hormones)
3) in the cell nucleus (thyroid hormones) number of receptors usually does not
remain constant (increase or decrease)
Intracellular Signaling
formation a hormone-receptor complex – alteration of function of receptor :
1) ion channel-linked receptors
2) G protein-linked hormone receptors
3) enzyme-linked hormone receptors
4) intracellular hormone receptors and activation of genes
1) Ion Channel-Linked Receptors
acetylcholine & norepinephrine change in the structure of the receptor opening or closing a channel for one or
more ions (Na, K, Ca) few directly, most indirectly by coupling
with G protein-linked or enzyme-linked receptors
2) G Protein-Linked Hormone Receptors
heterotrimeric GTP-binding proteins > 1000 known G protein-coupled receptors all have 7 transmembrane segments that
loop in and out of the cell membrane cytoplasmic tail is coupled to G protein
(include three parts – α, β, and γ subunits) binding of hormone – conformational
change in receptor – activation of G protein
activated G proteins1) open or close cell membrane ion channels
2) change the activity of an enzyme in the cytoplasm
G proteins binds GDP (α subunit) displacement of GDP by GTP causes the α
subunit to dissociate from the trimeric complex and to associate with other intracellular signaling proteins
inhibitory (Gi) & stimulatory (Gs) proteins
3) Enzyme-Linked Hormone Receptors
some receptors, when activated, function directly as enzymes or are closely associated with enzymes that they activate
pass through the membrane only once hormone-binding site on the outside of the
cell membrane
catalytic or enzyme-binding site on the inside
leptin receptor member of a large family of cytokine receptors that do
not themselves contain enzymatic activity but signal through associated enzymes
one of the signaling pathways occurs through a tyrosine kinase of the janus kinase (JAK) family, JAK2
4) Intracellular Hormone Receptors and Activation of Genes
steroid hormones, thyroid hormones, retinoid hormones, and vitamin D
receptors in the cytoplasm or nucleus binding with a specific regulatory
(promoter) sequence of the DNA – hormone response element
transcription of specific genes and formation of mRNA
Second Messenger Mechanisms
cAMP, cGMP calcium ions and associated calmodulin
4 binding sites for Ca, 3 or 4 changes its shape activation/inactivation of protein kinases phosphorylation of proteins (myosin light
chain kinase – smooth muscle contraction) products of membrane phospholipid
breakdown
could beGi
amplificationof the effect – cascade of reactions
phosphatidylinositol biphosphate
contraction,secretion
Steroid Hormones Increase Protein Synthesis
these proteins then function as enzymes, transport proteins, or structural proteins
aldosterone – for 45 minutes, protein which promote sodium reabsorption and potassium secretion
full action is delayed for at least 45 minutes-up to several hours or even day
Thyroid Hormones Increase Gene Transcription in the Cell Nucleus
thyroxine and triiodothyronine bind directly with receptor proteins in the
nucleus (activated transcription factors located within the chromosomal complex)
they control the function of the gene promoters
formation of many types of intracellular proteins
thyroid hormones can continue to express their control functions for days or even weeks
Measurement of Hormone Concentrations in the Blood extremely minute quantities (pg/mL) radioimmunoassay
production of antibody that is highly specific for the hormone to be measured is produced
small quantity of this antibody (smaller than total possible) is mixed with:
1) sample containing the hormone to be measured
2) appropriate amount of purified standard hormone that has been tagged with a radioactive isotope
error of 10 to 15 percent
Measurement of Hormone Concentrations in the Blood
ELISA (enzyme-linked immunosorbent assay)
1) it does not employ radioactive isotopes
2) much of the assay can be automated using 96-well plates
3) cost-effective and accurate method for assessing hormone levels
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