Chapter 40 Neuroendocrine Systems

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Chapter 40Neuroendocrine Systems

• Presentation by Rahnia Parker
• Neurobiology

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Overview

• Hypothalamus
• Hypothalamus Pituitary Target Organ Axis
  Systems
• Characteristics of systems
• Metabolism
• Growth
• Stress
• Reproduction
• Lactation and Maternal Behavior
• Sexual Behavior

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HYPOTHALAMUS

• Neuroendocrine organ that regulates many
  physiological functions including the
  neuroendocrine system
• Regulates many physiological functions
• Maintains homeostasis
• Acts as an integrator from every sensory and
  autonomic system related to internal and external
  environments
• Releases neuropeptides and neurotransmitters to
  targets in CNS and pituitary gland
• Cells are neuroendocrine cells (neuronal and
  endocrine features) that release hormones

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Hypothalamic pituitary connection

• Median eminance
• Hyphothalamus releases hormones into this
• This releases hormone in pulsatile manner into
  portal capillary system
• Anterior pituitary
• Has receptors that hormones from the median
  eminance can bind to
• Releases or inhibits hormones

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Hypothalamus Pituitary Target Organ Axis
Systems

• Neuroendocrine system has three levels
• Hypothalamic hormone stimulates or inhibits
  anterior pituitary hormone through median
  eminance
• Median eminance contains portal capillary
  vasculature to anterior pituitary
• Anterior pituitary hormone released into
  circulation
• Target organ regulated by hormone

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Receptors

• Specific receptors for hormones to bind to
• At pituitary for hypothalamic hormones
• Triggers cascade of biosynthetic and secretory
• Triggers synthesis and release of pituitary
  hormones
• feedback
• At target organs for pituitary hormones
• Increase or decrease synthesis and secretion of
  other hormones
• Causes physiological effects

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Hypothalamus Pituitary Target Organ Axis
Systems cont.

• Regulation of hypothalamus
• Feedback from CNS
• Feedback from hormones
• Characteristics of Neurohormone release
• Release hormones in pulsatile manner
• Prevents desensitization of receptors
• Ultradian intervals 1-2 hours
• Circadian 24 hr rhythm independent of light/dark
  cycles, driven by suprachiasmatic nucleus
• Diurnal 24 hr rhythm entrained to light/dark
  cycles

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System characteristics

• Five neuroendocrine axes
• Each having specialized cells at hypothalamus and
  specialized receptors for response
• Coordinate responses to environment or internal
  homeostatic stimuli
• Metabolism
• Growth
• Stress
• Reproduction
• Lactation

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Metabolism The Brain-Pituitary-Thyroid Axis

• Critical for development and survival
• Hypothalamic hormone is thyrotropin-releasing
  hormone (TRH)
• TRH neurons concentrated on paraventricular
  nucleus of hypo.
• At anterior pituitary, targets receptors on
  thyrotropes stimulating production of thyroid
  stimulating hormone (TSH)
• At thyroid gland, TSH targets receptors
  stimulating production of thyroxine (T4) and
  triiodothyronine (T3)
• T3 and T4 carried in circulation on binding
  globulins

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METABOLISM cont.

• Thyroid hormone critical for cellular metabolism
• Receptors located throughout brain, peripheral
  and autonomic nervous systems, pituitary gland,
  bone, muscle, liver, heart, testis, lung,
  placenta, and other tissues
• Major function to regulate basal metabolic rate
  and calorigenic responses
• In cells regulate ATP production in mitochondria
  and alter protein synthesis
• Hormones released in pulsatile manner as
  circadian rhythm (24 hr independent of l/d)
• TRH cleaved from prohormone and binds to
  receptor results in TSH gene transcription
• TSH receptor is seven transmembrane receptor
  mostly in thyroid gland binding with hormone
  activates cAMP generation stimulating production
  and release of thyroid hormone (T4 and T3)

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METABOLISM cont.

• Members of steroid family because of phenolic
  rings

• T3 has three iodides
• T4 has four iodides
• T4 more abundant but usually converts to T3
• Receptor is nuclear transcription factor
  activates or inhibits gene transcription

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METABOLISM cont.

• Thyroid hormone excess or insufficiency greatly
  affects CNS
• Excess
• Tremor, nervousness, tremulousness, insomnia and
  sleep disorders, impairments in memory and
  concentration, neuropsychiatric syndromes,
  seizure, chorea, and coma
• Insufficiency
• Sleep apnea, hypothermia, hypoventilation,
  neuropsychiatric syndromes, peripheral
  neuropathy, cerebellar ataxia, and coma
• Cretinism when insufficient thyroid hormone
  during fetal or early development
• Graves disease when hyperthyroidism occurs
  (goiter and bulging eyes)

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Growth The Somatotropic Axis

• Somatic growth and development of organisms
• Hypothalamic hormones are growth
  hormone-releasing hormone (GHRH) and
  somatostatin.
• Anterior pituitary hormone is growth hormone (GH)
  also called somatotropin
• Major role of growth hormone is in neonatal and
  postnatal growth, particularly pubertal growth
  spurt
• Also metabolic homeostasis
• Stimulates protein synthesis, increases
  lipolysis, influences carbohydrate metabolism,
  enhances glucose uptake and utilization, and has
  lipolytic effects
• Stimulates growth of organs, hormone production,
  skeletal growth and maturation, and immune
  functions

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GROWTH cont.

• Hormones released in pulsatile manner
• GHRH and somatostatin release coordinated at
  intervals of 1-3 hrs
• GH diurnal (24 hrs entrained l/d)
• Active GHRH binds to receptor synthesis of GH
• Somatostatin binds to receptor inhibit GH GH
  191 a.a. peptide containing two disulfide bonds
• IGF-I is major target for GH
• Affects outgrowth and nervous system development
• Important mediator of somatotropic axis
• Somatic growth and development is greatly
  affected by excess or deficiency of GH
• Insufficiency extremely short stature
• Excess gigantism, acromegaly

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Stress The Brain-Pituitary-Adrenal Axis

• Stress response
• Hypothalamic hormones are corticotropin-releasing
  hormone (CRH) and arginine vasopressin (AVP)
• Corticotropes receive and respond with synthesis
  and release of adrenocorticotropic hormone (ACTH)
  by pituitary gland
• ACTH acts on receptors at adrenal cortex
  stimulating production and release of
  glucocorticoids
• Major role is to mediate stress responses and
  affect cellular metabolism
• Stimulates enzymes in liver, gastrointestinal
  system, lungs, and adrenal medulla
• Mobilizes energy stores and improve
  cardiovascular tone
• Interacts with other neurohormones and can
  suppress growth axis and reproductive function
  and cause hyperthyroidism

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STRESS cont.

• Hormones released as circadian rhythm
• CRH acts with AVP to promote synthesis and
  release of ACTH
• ACTH from POMC cleavage affects adrenal cortex
  producing glucocorticoids
• Glucocorticoids members of steroid family
• Can bind to glucocorticoid receptor or
  mineralocorticoid receptor which both either
  stimulate or inhibit gene transcription
• Disruptions in the stress response balance can
  dysregulate the brain-pituitary-adrenal axis
• Overactivity increase susceptibility to
  infection and tumors, reduce inflammatory and
  autoimmune disease, and impair memory.
• Underactivity resistance to infection and tumors
  but increased susceptibility to inflammatory and
  autoimmune disease.

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Reproduction The Brain-Pituitary-Gonadal Axis

• Hypothalamus synthesize and release
  Gonadotropin-releasing hormone (GnRH)
• Anterior pituitary produces luteinizing hormone
  (LH) and follicle stimulating hormone (FSH)
• Gonads (ovaries and testes) produce sex steroids
  estrogen, progesterone, and testosterone
• GnRH systems becomes activated at puberty
• Achieve reproductive function ovulation in
  females and sperm production in males
• Hormones are released in pulsatile manner
• Weak diurnal rhythm (regulated developmentally)
• Higher during puberty, diminishes into adulthood

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REPRODUCTION cont.

• GnRH binds to seven transmembrane receptor and
  activates synthesis and release of gonadotropins
  (LH and FSH)
• Sex steroids are from cholesterols
• Pathway in figure

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Lactation and Maternal Behavior

• Prolactin from Pituitary cells lactotropes
• No known prolactin-releasing hormone (can be
  stimulated by TRH and GnRH associated peptide) in
  hypothalamus but dopamine inhibits release
• Prolactin causes milk synthesis and secretion in
  alveoli of mammary glands in response to suckling
  stimulus
• Can influence reproduction, and function in
  osmoregulation
• Higher levels in females than males (estrogen
  stimulates prolactin release)
• Hormone released in diurnal rhythm
• Member of somatotropin family similar to GH

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Review

• Five hypothalamus pituitary target organ
  systems regulated by hypothalamus
• Characteristics control
• Metabolism thyroid gland producing T3 and T4
  hormones
• Growth somatotropic affects producing Growth
  Hormone and IGF-I
• Stress adrenal cortex producing glucocorticoids
• Reproduction gonads producing sex steroids
  (estrogen, progesterone, and testosterone)
• Lactation production of prolactin to produce milk

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Sexual Behavior

• Sexual differentiation of the reproductive system
• Determination of sex by Y chromosome
• Presence of the Y chromosome develops testes,
  absence develops ovaries
• Internal genitalia determined by testosterone
  (maintains and promotes growth of Wolffian
  ducts-male internal genitalia) and AMH (causes
  regression of Mullerian ducts-female internal
  genitalia)
• Differentiation of the brain

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Sexual Behavior cont.

• Hormones and sexual behavior
• Male and female behavior
• Pheramones, the Vomeronasal Organ, and Sexual
  Behavior
• Pheramones are chemical signals used for
  communication between animals
• Important in coordinating physiology and behavior
• Conveys info about reproductive status, dominance
  status, or other social cues
• Released into environment
• Vomeronasal organ projection into olfactory bulbs
  allows detection of pheromones
• Contact medial amygdala, cortical regions, and
  bed nucleus of the stria terminalis which are
  implicated in sexual behavior