Physio Endocrine Intro (43)

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  1. 43 Intro
  2. Hormones
    • messengers in between cells & organs in the body that instruct the target tissue to perform a function that maintains homeostasis
    • means “to excite” in greek
  3. Classic Endocrine System
    endocrine organs have specialized cells that release hormones into the blood stream → hormones travel through the blood → are brought to/interact w/ their appropriate target tissue via highly specific receptors for that particular hormone
  4. Paracrine Signaling
    • a hormone producing cell releases hormones into the surrounding environment
    • eg. in the presence of a wound, platelets bind to the wound site & release their intracellular contents (PDGF, TGF-alpha, etc.); these locally released hormones call upon additional wound-repairing mechanisms
    • also an important type of signaling during DEVELOPMENT
  5. Autocrine Signaling
    • a hormone producing cell releases a hormone that it itself has surface receptors for
    • therefore it stimulates the receptors of its own cell
    • eg. important in tumor cell signaling (tumor cells can autostimulate growth)
    • also relevant for T-cells: when they recognize an antigen they produce IL-2 which is a growth factor for T-cells themselves
  6. Juxtacrine Signaling
    • when a hormone is displayed on the cell’s surface & only acts on another cell via direct physical interaction (w/ that other cell)
    • sort of a subcategory of paracrine signaling however rather than the hormones being soluble, cell-to-cell contact is necessary
  7. Intracrine Signaling (has a duel meaning)
    • 1. when a cell organelle releases a molecule that acts on a different organelle in that same cell
    • - eg. Inositol Triphosphate is released from the cell membrane & binds to receptors on the endoplasmic reticulum → signals a release of intracellular Ca2+

    2. occasionally a hormone that binds to a cell surface receptor will be taken up INTO that cell where it may itself have a separate biological function (eg. EGF ligand)
  8. What is considered the master regulator of endocrine physiology?
    • the brains of the endocrine system - the Hypothalamus & Pituitary
    • the hypothalamus can receive sensory input from the brain (as well as ion/glucose concentration info from the blood) & in response releases various releasing hormones that act on the pituitary gland
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  9. What are thyroid gland hormones largely mediating?
    • basal metabolic rate
    • T3, T4 (also produces calcitonin)
  10. Parathyroid Glands
    4 small adjacent & usually attached glands on either side of the thyroid that produce parathyroid hormone
  11. Parathyroid Hormone (PTH)
    INCREASES blood calcium (opposes the action of calcitonin) by increasing osteoclast activity (which breakdown bone & liberate calcium) & stimulating vitamin D activation in the kidney (stimulates calcium resorption in GI tract & kidney)
  12. A general principle of the endocrine system is:
    • there are feedback loops that maintain endocrine homeostasis
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  13. Thyroid System
    • hypothalamus releases TRH, acts on the AP
    • anterior pituitary releases TSH, acts on the thyroid
    • thyroid releases T3: it both performs its metabolic function & negatively feeds back on the production of TRH & TSH
  14. Trophic Hormones
    if a hormone is trophic, when it acts on a cell it also enlarges it
  15. What is a chronic inhibitor of prolactin release?
  16. Gigantism
    • an excessive production of growth hormone (GH) by the anterior pituitary before bone epiphyseal plate closure
    • eg. Robert Wadlow - world’s tallest man (8’ 11”) had a pituitary tumor that constitutively made growth hormone
  17. Acromegaly
    • GH excess (most likely due to tumor development) after closure of bone epiphyseal plates
    • it causes growth of soft tissues, apositional bone growth, & elevated blood glucose
    • bones become thick & coarse
  18. What is an additional effect of growth hormone?
    • it can DIRECTLY stimulate lipolysis of lipids in fat tissue (eg. seen in girl treated for low GH levels, her baby fat was lost)
    • GH’s effect on stature is an INDIRECT one: GH has receptors on liver & when bound cause production of IGF-1 → what actually causes bone length to increase
  19. Biological Assays
    • assays in which you look for some biological change in a cell culture or organism that can be used to detect the presence of a hormone - so it’s detected by looking for its ACTION
    • eg. EGF (epidermal growth factor) assay looked at its effect in newborn mice: mice injected w/ EGF would open their eyes sooner than mice not injected
    • this type of assay is less quantitative than would be desired
  20. Immunoassay
    • used to detect & quantitate the amount of a hormone in the blood stream or area of interest
    • eg. Radio Immunoassay for insulin
  21. Each hormone has a characteristic half-life in the blood stream:
    Image Upload 3
  22. Polypeptide Hormone Half-Lives
    tend to have 1/2 lives between minutes to an hour - interact w/ their specific cell membrane receptor, are taken up into the cell, transported to the lysosome, & degraded back into AAs (can also be broken down in the liver & excreted)
  23. Steroid Hormone Half-Lives
    have a somewhat longer 1/2 life, 1-2 hours - in order to degrade them they tend to be sulfonated/glucuronated (made more hydrophilic) in the liver or kidney then excreted into the urine
  24. AA Derivative Half-Lives
    • catecholamines/AA derived hormones have seconds long 1/2 lives in the blood stream
    • however some of the thyroid hormones (which are related to the catecholamines) have a MUCH longer 1/2 life, especially T4 (7 days)
    • these hormones are also sulfonated/glucuronated (made more hydrophilic) in the liver or kidney then excreted in the urine
  25. How are polypeptide hormones typically stored in their cells of origin?
    • in secretory vesicles - vesicles & the hormones they contain are prepositioned/premade
    • when signaled these vesicles fuse w/ the cell membrane & release their contents
    • the resulting response is RAPID
  26. How are steroid hormones synthesized?
    • steroid hormones are NOT stored but instead are all synthesized from cholesterol
    • cholesterol is first turned into Pregnenolone in the mitochondria
    • it then exits the mt & is acted upon by additional enzymes to form different steroid hormones
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  27. Hormone Binding Kinetics
    • equilibrium is determined by dividing the “on” (bound) rate divided by the “off” (unbound) rate
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    • dissassociation constant for a typical hormone = 1 nMol (10-9 molar)
    • at the concentration of a nanomolar if a hormone had a dissociation constant of of 10-9, that’s when half the hormone is bound to the receptor & half of it is free & unbound
  28. Law of Mass Action
    • as the hormone concentration is increased, more hormone will bind to its given receptor
    • decreasing the amount of hormone will decrease the amount of hormone-receptor complex found
    • physiologically the latter is accomplished via hormone binding proteins
  29. Hormone-binding Proteins
    • serve as a means of PRESERVING a reserve of hormone
    • as free hormone is used & taken up by cells, bound hormone can be RELEASED from its binding protein to maintain equilibrium
  30. How Steroid Hormones Function
    • they diffuse through cell membranes
    • enter the nucleus & bind to receptors that once activated go on to regulate transcription
    • *thyroid hormone receptors are also like steroid hormone receptors in that they’re located in cells’ nucleus
  31. How Polypeptide Hormones Function
    bind to surface receptors that activate signal transduction processes (that affect cellular function)
  32. Which hormone has a tyrosine kinase receptor?
    • Insulin
    • while prolactin & GH both have tyrosine kinase ASSOCIATED receptors called JAK kinases, the hormones don’t bind directly to a tyrosine kinase receptor
    • the insulin cell membrane receptor IS coded by a gene that is a tyrosine kinase…
  33. 44 Signaling
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Physio Endocrine Intro (43)
Exam 4
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