Hormone%20??

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Hormone ??

• PROGRAM KEDOKTERAH HEWAN
• UNIVERSITAS BRAWIJAYA

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Biological function at each level of organization
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Course Outline

• Hormone Definition ,classification dan Fungsi

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Endocrine System

• Endocrine glands are ductless
• Exocrine glands have ducts

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What is a Hormone

• A specific chemical compound
• Produced by a specific tissue of the body
• Where it is released in the body fluids
• And carried to a distant target tissue
• Where it affects a pre-existing mechanism
• And is effective is small amounts.

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Definition

• They are the chemical integrators of a
  multicellular existence, coordinating activities
  from daily maintenance to reproduction and
  development.

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Hormone

• Substance produced by endocrine gland
• Acts on cells, tissues or organs at a place other
  than where produced
• Acts as a catalyst.

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Produced by a specific tissue

• Major Endocrine Organs are
• Hypothalamus
• Pituitary gland
• Thyroid gland
• Parathyroid gland
• Thymus
• Adrenal gland
• Pancreas
• Ovaries
• Testes

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Classification

• Hormones can be classified by several properties
• 1. Classification by site of action.
• 1.1. Autocrine secretion - substance released by
  cell that affects the secreting cell itself
• (e.g. norepinephrine is released by a
  neurosecretory cell in the adrenal medulla, and
• norepinephrine itself inhibits further release by
  that cell - this is also an example of direct
  negative feedback)

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Endocrine Glands

• Paracrine secretions
• act locally
• affect only neighboring cells

• Endocrine glands
• release hormones
• hormones travel through blood to target cells

• Autocrine secretions
• affect only the secreting cell

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Endocrine Glands
Ovary
Hypothalamus
Adrenal
Pineal
Uterus
Pituitary
Placenta
Testes (in bull)
Thyroid
Pancreas
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Classification and Properties of Hormone

• A. Site of Production
• B. Type of action
• 1. Primary hormone of reproduction
• 2. Metabolic hormone
• C. Chemical Structure
• 1. General structure
• Proteins and polypeptides
• Steroids
• Fatty acids
• Modified amino acid
• 2. Size

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• Paracrine secretion
• substance released by cell that affects
  neighboring cells.
• Not released into bloodstream (e.g. histamine
  released at site of injury to constrict blood
  vessel walls and stop bleeding)
• Endocrine secretion
• - substance released by cell into bloodstream
  that affects distant cells.

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Types of cell-to-cell signaling
Classic endocrine hormones travel via bloodstream
to target cells neurohormones are released via
synapses and travel via the bloostream paracrine
hormones act on adjacent cells and autocrine
hormones are released and act on the cell that
secreted them. Also, intracrine hormones act
within the cell that produces them.
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ANATOMICAL classification

• Hypothalamus
• Somatostatin Growth hormone releasing hormone
  (GHRH)Thyrotropin releasing hormone (TRH)
  Gonadotropin releasing hormone (GnRH)
  Corticotropin releasing hormone (CRH) Prolactin
  releasing hormone (PRH)Dopamine (PIH)

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Function of Hypothalamus

• appetite
• thirst
• body temperature
• vasomotor activity
• emotion
• use of body nutrient reserves
• activity of intestine
• sleep
• sexual behavior
• Production and release of releasing hormones

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Cells of the Anterior Pituitary
Hypothalamus
Preoptic nuclei cell
Nerve Cells
Superior hypophyseal artery
Capillary plexus
Hypophyseal portal vessels
Posterior pituitary

• LH
• FSH
• Prolactin
• STH
• TSH
• ACTH

Capillary plexus
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Hypothalamus
Nuclei that produce posterior pituitary hormones
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Pituitary Gland Control

• Hypothalamic releasing hormones stimulate cells
  of anterior pituitary to release hormones
• Nerve impulses from hypothalamus stimulate nerve
  endings in the posterior pituitary gland to
  release hormones

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Anterior Pituitary Hormones

• A. Structure
• 1. glycoproteins or proteins
• B. Hormones
• 1. gonadotropins
• Follicle stimulating hormone (FSH)
• Luteinizing hormone (LH)
• Prolactin

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Anterior Pituitary Hormones

• 2.Other trophic hormones
• Adrenal Corticotropin (ACTH)
• thyroid stimulating hormone (TSH)
• growth hormone (GH or STH)

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Anterior pituitary gland

• Growth hormone (hGH)
• Thyroid stimulating hormone(TSH)
• Gonadotropins (FSH and LH)
• Adrenocorticotropic hormone (ACTH)
• Prolactin Melanocyte stimulating hormone (MSH)

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Posterior pituitary gland

• Antidiuretic hormone (ADH, or vasopressin)
• Oxytocin

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Thyroid Gland
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Thyroid gland

• Thyroid hormones (T3 and T4)
• Calcitonin
• Parathyroid glands
• Parathyroid hormone (PTH)

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Thyroid Gland Hormones
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Disorders of the Thyroid Gland
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Thyroid hormones
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Adrenal cortex

• Cortisol
• AldosteroneDehydroepiandrosterone (DHEA)
• Adrenal medulla
• Adrenalin (or epinephrine)Noradrenalin (or
  norepinephrine)

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Kidney

• Erythropoietin
• 1,25 Dihydroxy Vit D3
• Renin / angiotensin I
• Pancreas
• Insulin
• Glucagon

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Liver

• Insulin-like growth factor (IGF I) or
  somatomedin
• Stomach
• Gastrin
• Duodenum
• Secretin
• Cholecystokinin (CCK)

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Gonads

• Sex hormones
• Oestrogen,
• progesterone,
• testosterone.

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Classification and Properties of Hormone

• Chemical Structure
• Polypeptides - hypothalamic
• Protein - pituitary, gonad
• Steroids - gonad, adrenal
• Fatty acid - many sources, prostaglandins
• Modified amino acid - pineal

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Chemistry of Hormones

• Steroid or Steroid-Like Hormones
• sex hormones
• adrenal cortex hormones

• Nonsteroid Hormones
• amines
• proteins
• peptides
• glycoproteins
• most hormones

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Chemical Structure of Hormones
polypeptide modified amino acid protein sex
steroid fatty acid GnRh melatonin LH
Estradiol PGF TRH FSH Progesterone CRH Prolact
in Testosterone GHRH ACTH Somatistatin TSH Oxyto
cin GH or STH Relaxin Inhibin
2?
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Chemical Structure of Hormones
Molecular size of hormones that regulate
reproduction
Hormone Molecular Weight

• FSH 30,000 to 37,000
• LH 26,000 to 32,000
• Prolactin 23,000 to 25,000
• HCG 37,700
• eCG 28,000
• Inhibin gt10,000
• Relaxin 6,500
• ACTH 4,500
• Oxytocin 1,007
• GnRH 1,200
• Estradiol 300
• Testosterone 300
• Progesterone 300
• PGF 300

2?
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Chemical Structure of Hormones Cont.

• Polypeptide and protein hormones
• are made of peptide bonds

These hormones can not be given orally!
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Chemical Structure of Hormones Cont.

• Steroids

PROGESTERONE
CORTISOL
These hormones can be given orally!
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Types of Hormones
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Structural Formulas of Hormones
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Hormones chemical structure and synthesis

1. Proteins and polypeptides the anterior and
   posterior pituitary gland hormones, the pancreas
   (insulin, glucagon), the parathyroidal gland
   (parathyroidal hormone), etc.
2. Steroids the adrenal cortex (cortisol,
   aldosterone), the ovaries (estrogen,
   progesterone), the testes (testosterone), the
   placenta (estrogen, progesterone)
3. Derivates of amino acid tyrosine the thyroid
   gland (thyroxine, triiodothyronine), the adrenal
   medullae (epinephrine, norepinephrine)

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Polypeptide and protein hormones

• Most of the hormones in the body.
• Protein 100 of more amonoacids
• Peptides less than 100 aminoacids
• Synthesized in the rough endoplasmatic reticulum
  as preprohormones ? prohormones ? transferred to
  Golgi apparatus ? secretory vehicles ? hormones
  (enzymatic fission) ? exocytosis
• Water soluble easy reaching the target tissue
  by circulatory system

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Steroid hormones

• Usually synthesized from cholesterol
• Not stored, but possible quick utilization from
  cholesterol in the blood
• Lipid soluble diffuse across the cell membrane
  ? interstitial fluid ? blood

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Steroid hormones

• All steroid hormones are derived from cholesterol
  and differ only in the ring structure and side
  chains attached to it.
• All steroid hormones are lipid soluble

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Types of steroid hormones

• Glucocorticoids cortisol is the major
  representative in most mammals
• Mineralocorticoids aldosterone being most
  prominent
• Androgens such as testosterone
• Estrogens, including estradiol and estrone
• Progestogens (also known a progestins) such as
  progesterone

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Steroid hormones

• Are not packaged, but synthesized and immediately
  released
• Are all derived from the same parent compound
  Cholesterol
• Enzymes which produce steroid hormones from
  cholesterol are located in mitochondria and
  smooth ER
• Steroids are lipid soluble and thus are freely
  permeable to membranes so are not stored in cells

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Steroid hormones

• Steroid hormones are not water soluble so have to
  be carried in the blood complexed to specific
  binding globulins.
• Corticosteroid binding globulin carries cortisol
• Sex steroid binding globulin carries testosterone
  and estradiol
• In some cases a steroid is secreted by one cell
  and is converted to the active steroid by the
  target cell an example is androgen which
  secreted by the gonad and converted into estrogen
  in the brain

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Steroids can be transformed to active steroid in
target cell
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Steroidogenic Enzymes
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Steroid hormone synthesis
All steroid hormones are derived from
cholesterol. A series of enzymatic steps in the
mitochondria and ER of steroidogenic tissues
convert cholesterol into all of the other steroid
hormones and intermediates. The rate-limiting
step in this process is the transport of free
cholesterol from the cytoplasm into mitochondria.
This step is carried out by the Steroidogenic
Acute Regulatory Protein (StAR)
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Steroid hormone synthesis

• The cholesterol precursor comes from cholesterol
  synthesized within the cell from acetate, from
  cholesterol ester stores in intracellular lipid
  droplets or from uptake of cholesterol-containing
  low density lipoproteins.
• Lipoproteins taken up from plasma are most
  important when steroidogenic cells are
  chronically stimulated.

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LH
Extracellularlipoprotein
Cholesterolpool
acetate
ATP
cAMP
cholesterol
PKA
Pregnenolone
3bHSD
Progesterone
P450c17
Androstenedione
17bHSD
TESTOSTERONE
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Cholesterol is a 17 ketosteroid and an important
precursor for all steroid hormones.
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Actions of Steroid Hormones

• hormone crosses membranes

• hormone combines with receptor in nucleus

• synthesis of mRNA activated

• mRNA enters cytoplasm to direct synthesis of
  protein

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Actions of Steroid Hormones
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Actions of Nonsteroid Hormones

• hormone binds to receptor on cell membrane

• adenylate cyclase activated

• ATP converted to cAMP

• cAMP promotes a series of reactions leading to
  cellular changes

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Actions of Nonsteroid Hormones
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Amino hormones

• Derivatives from tyrosine
• The thyroid hormones
• Synthesized and stored in follicules in the
  thyroid gland as thyreoglobulin ? free hormone to
  the blood ? connection to plasma proteins
  (thyroxine-binding globulin)
• Adrenal medullary hormones
• Stored in vesicles ? exocytosis ? in the blood as
  a free hormone or in combination with different
  substances

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Amine Hormones

• Two other amino acids are used for synthesis of
  hormones
• Tryptophan is the precursor to serotonin and the
  pineal hormone melatonin
• Glutamic acid is converted to histamine

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Fatty Acid Derivatives - Eicosanoids

• Arachadonic acid is the most abundant precursor
  for these hormones. Stores of arachadonic acid
  are present in membrane lipids and released
  through the action of various lipases. The
  specific eicosanoids synthesized by a cell are
  dictated by the battery of processing enzymes
  expressed in that cell.
• These hormones are rapidly inactivated by being
  metabolized, and are typically active for only a
  few seconds.

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Fatty Acid Derivatives - Eicosanoids

• Eicosanoids are a large group of molecules
  derived from polyunsaturated fatty acids.
• The principal groups of hormones of this class
  are prostaglandins, prostacyclins, leukotrienes
  and thromboxanes.

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Regulation of hormone secretion

• Sensing and signaling a biological need is
  sensed, the endocrine system sends out a signal
  to a target cell whose action addresses the
  biological need. Key features of this stimulus
  response system are
•         receipt of stimulus
•         synthesis and secretion of hormone
•         delivery of hormone to target cell
•         evoking target cell response
•         degradation of hormone

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Prostaglandins

• paracrine substances
• act locally
• very potent in small amounts
• regulate cellular responses to hormones
• can activate or inhibit adenylate cyclase
• controls cAMP production
• alters cells response to hormones
• wide variety of functions

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Hormone secretion and blood concentration

• Norepinephrine, epinephrine -secreted within
  seconds after the gland is stimulated and develop
  full action within another few seconds to minutes
• Thyroxine or growth hormone require months to
  full effect
• Rates of secretion µg mg / day
• Concentration in the blood pg - µg / ml of blood

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Feedback control of hormone secretion - Negative
feedback

• Prevents overactivity of hormone system
• The control variable is often not the secretory
  rate of the hormone itself but the degree of
  activity of the target tissue
• Feedback regulation of hormones can occur at all
  levels, including gene transcription and
  translation steps involved in processing the
  hormone or releasing the stored hormone
• HPA axis (hypothalamo-pituitary-adrenal axis)
  complex negative feedback

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Control of Hormonal Secretions

• primarily controlled by negative feedback
  mechanism

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Negative Feedback
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Complex negative feedback
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Feedback control of hormone secretion - Positive
feedback

• Just in a few instances
• Positive feedback occurs when the biological
  action of the hormone causes additional secretion
  of the hormone
• Secretion of LH (luteinizing hormone) based of
  the stimulatory effect of estrogen before
  ovulation LH stimulates ovaries to produce more
  estrogen and it stimulates again the pituitary
  gland to produce LH. When the LH reaches the
  appropriate concentration the negative feedback
  occurs

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Hormone release

• Cyclical variation influenced by seasonal
  changes, stages of development and aging,
  circadial cycle, sleep etc.
• STH (growth hormone) development, ? during
  early period of sleep, ? during later stages of
  sleep
• Gonadal hormones - development and aging,
  seasonal changes, lunar cycles
• ACTH, glucocorticoids etc. circadial cycle
• Reflex release influenced by stress and new
  situations
• Stress hormones corticoids, renin-angiotensin-al
  dosterone system, prolactin

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Transport of hormones in the blood

• Water-soluble hormones (peptides and
  catecholamines) dissolved in the plasma,
  diffusion from capillaries to the interstitial
  fluid and to target cells
• Lipid soluble (steroid hormones) and thyroid
  hormones circulate in the blood mainly bound to
  plasma proteins (less then 10 as free hormones).
  
• Thyroxine more than 99 bound to plasma
  proteins.
• Hormones bound to proteins are biologically
  inactive (reservoir) until they dissociate from
  plasma proteins

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Clearance of hormones from the blood

• Clearance rate of disappearance from plasma /
  concentration in plasma (measuring by radioactive
  hormone)
• Ways to clear hormones from plasma
• Metabolic destruction by the tissue (enzymes)
• Binding with the tissue (some hormones may be
  recycled)
• Excretion by the liver into the bile (steroid
  hormones), long-time life period because they are
  bound to plasma proteins half-life of thyroid
  hormones 1-6 days
• Excretion by the kidneys into the urine (peptide
  hormones and catecholamines water soluble
  short-time life period)

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Hormone receptors

• Location
• In or on the surface of the cell membrane
  proteins, peptides, catecholamines
• In the cell cytoplasm steroid hormones
• In the cell nucleus Thyroid hormones
• Hormonal receptors are large proteins
• Each cell has 2 000 100 000 receptors
• Receptors are usually highly specific for single
  hormone
• The number of receptors does not remain constant
  (from day to day, even from minute to minute).
  Receptors are inactivated or destroyed
  (down-regulation) and reactivated or produced new
  ones (up-regulation).

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Intracellular signaling after hormone receptor
activation

• Different ways of hormone action
• Change of membrane permeability (ionotropic
  receptors), opening and closing ion channels
  (Na, K, Ca2)of postsynaptic receptors
  acetylcholine, norepinephrine
• Activation of intracellular enzyme
• Kinase promotes phosphorylation insulin
• Adenyl cyclase catalyzes the formation of cAMP
  (cyclic adenosine monophosphate) or cGMP (cyclic
  guanosin monophosphate) second messengers
• Binding with intracellular receptors steroid
  and thyroid hormones hormone-receptor complex
  activates specific portion of DNA and this
  initiates transcription of specific genes to form
  mRNA protein synthesis (long-term process)

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The adenylyl cyclase cAMP second messenger
system

• Hormones
• ACTH (Adrenocorticotropic hormone)
• Angiotensin II (epithelial cells)
• Calcitonin
• Catecholamines (ß receptors)
• CRH (Corticotropin-releasing hormone)
• FSH (Follicle-stimulating hormone)
• Glucagon
• HCG (Human chorionic gonadotropin)
• LH (Luteinizing hormone)
• PTH (Parathyroid hormone)
• Secretin
• TSH (Thyroid-stimulating hormone)
• Vasopressin (V2 receptor, epithelial cells)

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The cell membrane phospholipids second messenger
system

• Hormones
• Angiotensin II (vascular smooth muscles)
• Catecholamines (a receptor)
• GRH (gonadotropin-releasing hormone)
• GHRH (Growth hormone-releasing hormone)
• Oxytocin
• TRH (Thyroid-releasing hormone)
• Vasopressin (V1 receptor, vascular smooth muscle)

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Hormones acting on the genetic machinery of the
cell (1)

• Steroids
• Steroid hormone enters the cytoplasm of the cell
  and binds to receptor protein (HSP
  heat-shock-protein)
• Receptor protein-hormone complex diffuses or is
  transported into the nucleus
• The complex binds to the DNA and activates the
  transcription process of specific genes to form
  mRNA
• mRNA diffuses into the cytoplasm, promotes
  translation process at the ribosomes and forms
  new proteins
• Example Aldosterone (mineralocorticoid from
  adrenal cortex) acting in renal tubular system.
  The final effect delays hours after aldosterone
  enters the cell.

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Hormones acting on the genetic machinery of the
cell (2)

• Thyroid hormones
• Hormones bind directly with receptor proteins in
  the nucleus
• Those proteins are probably protein molecules
  located within the chromosomal complex
• Function of thyroid hormones
• They activate the genetic mechanisms for the
  formation of many types of intracellular proteins
  (100 or more) many of them are enzymes that
  control intracellular metabolic activity
• Their function of this control may last for days
  or even weeks

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Measurement of hormone concentration in the blood

• Radioimmunoassay
• Hormone specific antibody is mixed with
• Animal fluid (serum) containing the hormone
• Standard hormone marked by radioactivity
• Hormones (animals and standard) compete for this
  antibody
• Result
• More radioactive hormone-antibody complex (after
  separation) little animals hormones
• Less radioactive hormone-antibody complex (after
  separation) lot of animals hormones

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Homeostasis function of hormones (1)

• Osmolality (280-300 mosm/l)
• Aldosterone, antidiuretic hormone, insulin
• Acid-base balance (bases 145-160 mmol/l,
  bicarbonate 24-35 mmol/l, pH 7.4 0.4)
• Aldosterone, antidiuretic hormone, insulin
• Ions in blood
• Na (130-148 mmol/l) aldosterone, cortisol,
  atrial natriuretic peptide
• K (3.8-5.1 mmol/l) aldosterone, cortisol
• Ca2 (2.25-2.75 mmol/l) parathormone,
  calcitriol, calcitonin
• Phosphates (0.65-1.62 mmol/l) - parathormone,
  calcitriol, calcitonin
• Mg2 (0.75-1.5 mmol/l) - parathormone, calcitriol
• Cholesterolemia (4-6 mmol/l)
• Gonadal hormones, thyroxine, trioidothyronine
• Proteinemia (64-82 g/l, albuminemia 35-55 g/l)
• Gonadal hormones, growth hormone,
  trioidothyronine, cortisol
• Glykemia (3.9-6.7 mmol/l)
• Insulin, glucagon, cortisol, adrenalin, growth
  hormone

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Homeostasis function of hormones (2)

• Energetic and oxygen metabolism (basal metabolism
  1800 kcal/day, 7600 kJ/day)
• ? - thyroxine, trioidothyronine, epinephrine,
  norepinephrine, glucagon, cortisol
• ? - insulin
• Blood pressure (120/80 mmHg)
• ? - angiotensin, epinephrine, norepinephrine,
  aldosterone, glucocorticoids
• ? - Atrial natriuretic factor, NO, kinins,
  endothelial relaxating factor

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Hormone Receptors

• A hormone receptor is a receptor protein on the
  surface of a cell or in its interior that binds
  to a specific hormone. The hormone causes many
  changes to take place in the cell.
• Binding of hormones to hormone receptors often
  trigger the start of a biophysical signal that
  can lead to further signal transduction pathways,
  or trigger the activation or inhibition of genes

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Types of Hormone Receptors

• Peptide hormone receptors are often transmembrane
  proteins. They are also called G-protein-coupled
  receptors, sensory receptors or ionotropic
  receptors. These receptors generally function via
  intracellular second messengers (cAMP)

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• Steroid hormone receptors and related receptors
  are generally soluble proteins that function
  through gene activation. These are plasma
  membrane, cytosol and nucleus. They are generally
  intracellular receptors.

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• Types of receptors Type I Receptors Sex
  hormone receptors (sex hormones) Glucocorticoid
  receptor (glucocorticoids) Mineralocorticoid
  receptor (mineralocorticoids)
• Type II Receptors Thyroid hormone receptor

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