Endocrine Glands:

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Chapter 11
Endocrine Glands Secretion and Action of Hormones
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Endocrine Glands

• Are ductless and secrete chemical hormones into
  bloodstream
• Hormones act upon target cells that contain
  receptor proteins for them
• Neurohormones are secreted into blood by
  specialized neurons

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Chemical Classification of Hormones

• Amines are derived from tyrosine or tryptophan
  (amino acids)
• Include norepinephrine, epinephrine, thyroxine,
  melatonin
• Polypeptide/protein hormones are chains of amino
  acids
• Include antidiuretic hormone (ADH), growth
  hormone (GH), insulin, oxytocin, glucagon,
  adrenocorticotropic hormone (ACTH)
• Glycoprotein hormones are proteins with attached
  carbohydrates
• include luteinizing hormone (LH), follicle
  stimulating hormone (FSH), thyroid stimulating
  hormone (TSH)
• Steroids are lipids derived from cholesterol
• Include the sex hormones, aldosterone and
  cortisol

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Chemical Classification of Hormones continued

• Steroid and thyroid hormones are lipids
• Can diffuse into target cells
• The 2 major thyroid hormones are shown in Fig
  11.3

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Precursors

• Prohormones are precursors of hormones changed
  into the functional hormone by the gland before
  secretion into blood
• e.g. proinsulin
• Prehormones are precursors of hormones secreted
  by gland and changed into the functional hormone
  by the target tissue
• e.g. thyroxine (T4) is inactive until converted
  to T3 in target cells

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Hormone Interactions

• Synergistic hormones working together to produce
  an effect
• Produce a larger effect together than individual
  effects added together (epinephrine and
  norepinephrine on heart)
• Permissive effect if hormone enhances
  responsiveness of a target tissue to 2nd hormone
• estrogen upon uterus for progesterone
• Antagonistic if action of 1 hormone inhibits or
  opposes effect of another
• glucagon and insulin

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Hormone Concentration and Tissue Responses

• Normal tissue responses are produced only when
  hormones are in normal physiological range
• High (pharmacological) doses can cause of side
  effects
• Probably by binding to receptors of other
  hormones

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Hormone Concentrations and Tissue Responses
continued

• Priming effect (upregulation) occurs when a
  hormone induces more of its own receptors in
  target cells
• Results in a greater response
• Desensitization (downregulation) occurs after
  long exposure to high levels of a polypeptide
  hormone
• Subsequent exposure to this hormone produces a
  lesser response
• Due to decrease in of receptors on target cells
• Most peptide hormones have pulsatile secretion
  which prevents downregulation

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Steroid Hormones Bind to Nuclear Receptor
Proteins

• Lipid (nonpolar) hormones travel in blood
  attached to carrier proteins
• They dissociate from carriers and pass thru
  plasma membrane of
• target cell
• Receptors are called nuclear receptor proteins
• Receptor-hormone complex binds to DNA gene and
  activates transcription

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Mechanism of Thyroid Hormone Action

• Thyroid secretes 90 T4 (thyroxine) and 10 T3
• 99.96 of T4 in blood is bound to carrier protein
  (thyroid binding globulin)
• Only free T4 can enter cells, so the bound is
  reservoir
• T4 converted to T3 inside target cell
• T3 then binds to receptor protein located in
  nucleus

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Mechanisms of Steroid Hormones

• HRE consists of 2 half-sites
• 2 ligand-bound receptors have to bind to each HRE
  (dimerization)
• This stimulates transcription of target gene

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Mechanism of Thyroid Hormone Actioncontinued

• T3 and receptor bind to 1 half-site
• Other half-site binds retinoic acid
• Two partners form heterodimer that activates
  hormone response element on DNA
• Stimulates transcription of target gene

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Polar Hormones Use 2nd Messengers

• Water soluble hormones must use cell surface
  receptors because they cannot pass directly
  plasma membrane
• Actions are mediated by 2nd messengers
• Hormone is extracellular signal (1rst messenger)
• 2nd messenger carries signal from receptor to
  inside of cell

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Adenylate Cyclase-cAMP 2nd Messenger System

• Hormone binds to receptor causing dissociation of
  a G-protein subunit

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Adenylate Cyclase-cAMP continued

• G-protein subunit binds to and activates
  adenylate cyclase
• Which converts ATP into cAMP
• cAMP attaches to inhibitory subunit of protein
  kinase

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Adenylate Cyclase-cAMP continued

• Inhibitory subunit dissociates, activating
  protein kinase
• Which phosphorylates enzymes that produce
  hormones effects
• cAMP inactivated by phosphodiesterase

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Phospholipase-C Ca2

• Serves as 2nd messenger system for some hormones
• Hormone binds to surface receptor, activates
  G-protein, which activates phospholipase C

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Phospholipase-C Ca2

• Phospholipase C splits a membrane phospholipid
  into 2nd messenger IP3
• IP3 diffuses through cytoplasm to ER
• Causing Ca2 channels to open

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Phospholipase-C Ca2 continued

• Ca2 diffuses into cytoplasm and binds to and
  activates calmodulin

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Ca2-Calmodulin activates protein kinases which
phosphorylate enzymes that produce hormone's
effects
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Anterior Pituitary Gland

• Secretes 6 trophic hormones that maintain size of
  targets
• High blood levels cause target tissue to
  hypertrophy
• Low levels cause atrophy

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Anterior Pituitary continued

• Release of A. Pit. hormones is controlled by
  hypothalamic releasing and inhibiting factors and
  by feedback from levels of target gland hormones

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Posterior Pituitary Gland

• Posterior pituitary stores and releases the
  hormones vasopressin and oxytocin that are made
  in the hypothalamus

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Adrenal Glands

• Sit on top of kidneys
• Each consists of outer cortex and inner medulla

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Thyroid Gland

• Is located just below the larynx
• Secretes T4 and T3 which set BMR and are needed
  for growth, development

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Parathyroid Glands

• Are 4 glands embedded in lateral lobes of thyroid
  gland
• Secrete Parathyroid hormone (PTH)
• Most important hormone for control of blood Ca2
  levels

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Pineal Gland

• Secretes melatonin in response to activity of
  suprachiasmatic nucleus of hypothalamus
• Melatonin is involved in aligning physiology with
  sleep/wake cycle and seasons

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Thymus

• Produces T cells of immune system and hormones
  that stimulate them

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Autocrine and Paracrine Regulation

• Autocrine regulators are produced and act within
  same tissue of an organ
• All autocrines control gene expression in target
  cells
• Paracrine regulators are autocrines that are
  produced within one tissue and act on different
  tissue in same organ.
• Autocrines and paracrines include
• Cytokines (lymphokines, interleukins)
• Growth factors (promote growth and cell division)
  
• Neutrophins (provides trophic support for normal
  and regenerating neurons)

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