Endocrine System

Glands:

Hormone Release:

blood levels of hormones

  • Negative feedback control (body adjust if out of range/setpoint until it doesn’t need to)

  • hormone release triggered by:

    • Endocrine gland stimuli

    • Nervous system

  • Positive feedback:

Endocrine Gland Stimuli:

Endocrine glands are stimulated to synthesize and release hormones in response to one of three stimuli

  • Humoral stimuli: changing blood levels of ions and nutrients directly stimulate secretion of hormones

    • Ex: Ca2+ in blood

  • Neutral stimuli: nerve fibers stimulate hormone release

    • nervous system fibers stimulate adrenal medulla to secrete catecholamines (epi & norepi)

  • Hormonal stimuli: hormones stimulate other endocrine organs to release their hormones

    • Hypothalamic hormones stimulate release of most anterior pituitary hormones

    • Anterior pituitary hormones stimulate targets to secrete additional hormones

    • Hypothalamic-pituitary-target endocrine organs feedback loop

      • hormones from final target organs inhibit release of anterior pituitary hormones

Nervous System Modulation:

Nervous system adjusts to hormone levels

  • modify stimulation/inhibition of endocrine glands

Can override normal endocrine controls

  • Ex: severe stress, hypothalamus and nervous system override insulin to allow blood glucose levels or increase

    • prepares body for “fight or flight”

Target Cell Specificity:

  • Target cells must have specific receptors to which hormone binds

    • ex: ACTH receptors on certain cells of adrenal cortex, but thyrozin receptors are found on nearly all cells of body

  • Target Cell activation depends on three factors:

    1. blood levels of hormone

    2. relative number of receptors on/in target cell

    3. Affinity (strength) of binding between receptor and hormone

  • Amount of hormone can influence number of receptors for that hormone

    • Up-regulation: target cells form more receptors in response to low hormone levels

    • Down-regulation: target cells lose receptors in response to high hormone levels

      • desensitizes the target cells to prevent hem from overreacting to persistently high levels of hormone

Half-Life, Onset, And Duration of Hormone Activity:

  • hormones circulate in blood either free or bound

    • steroids and TH attached to plasma proteins

    • all other circulate without carriers

  • COncentration of circulating hormone reflects:

    1. rate of release

    2. speed at which it is inactivated and removed

  • Hormones can be removed blood by:

    • degrading enzymes or

    • kidneys or liver

      • Half-life: time required for level of hormone in blood level to decrease by half

Action of Hormones:

Hormone action on target cells:

  • alter plasma membrane permeability and/or membrane potential -open or close ion channels

  • stimulate synthesis of enzymes or other proteins

  • activate or deactivate enzymes

  • induce secretory activity

  • stimulate mitosis

Two main second-messenger systems:

  • Cyclic AMP (cAMP) signaling mechanism: ex. epinephrine - water soluble

    1. hormone (first messenger) binds to receptor

    2. receptor activates a G protein

    3. G protein activities or inhibits effector enzyme adenylate cyclase

    4. adenylate cyclase then conversation ATP to cAMP (second messenger)

    5. cAMP activates protein kinases that phosphorylate (adda phosphate) other proteins

  • PIP2 - calcium signaling mechanism (phosphatidylinositol 4,5-bisphosphate): ex. angiotensin pathway - regulates blood press.

    1. hormone-activated G protein activates: phospholipase C

    2. splits membrane protein, PIP2, into two second messengers:

      • diacylglycerol (DAG) activates protein kinases

      • inositol trisphosphate (IP3) causes Ca2+ release from intracellular storage sites

    3. calcium ions act as another second messenger

      • alters enzyme activity and channels, or binds ot regulatory protein calmodulin

      • calcium-bound calmodulin activates enzymes that amplify cellular response

Intracellular Receptors and Direct Gene Activation:

  • lipid-soluble steroid hormones and TH

  • diffuse into target cells

  • bind with intracellular receptors

  • enters nucleus and binds to region of DNA

  • initiate DNA transcription to produce mRNA

  • mRNA translated into specific protein

    Exs: metabolic activities, structural purposes, or exported from cell

Chemical Messengers:

  • Hormones: long-distance chemical signals; travel in blood or lymph

  • Autocrines: exert effect on the same cells that secrete them

  • Paracrines: locally acting, affecting cells other than those that secrete them

  • Autocrines and paracrines - local chemical messengers; not considered part of the endocrine system

Anterior Pituitary Hormones:

  • Growth Hormone (GH)

    • also called somatotropin as it is produced by somatotropic cells

    • has direct actions on metabolism and indirect growth-promoting actions

    • direct actions on metabolism

      • glucose-sparing actions decrease the rate of cellular glucose uptake and metabolism (anti-insulin effects)

      • triggers liver to break down glycogen into glucose

      • increases blood level so fatty acids for use as fuel and encourages cellular protein synthesis

    • Indirection actions on growth:

      • GH triggers liver, skeletal muscle, and bone to produce insulin-like growth factors (IGFs)

      • IGFs then stimulate:

        • cellular uptake of nutrients used to synthesize DNA and proteins needed for cell division

        • formation of collagen and deposition of bone matrix

        • GH

      • GH stimulates most cells to enlarge and divide, but major targets are bone and skeletal muscle

    • Regulation of Secretion:

      • GH release or inhibition chiefly regulated by hypothalamic hormones on somatotropic cells

        • Growth hormone-releasing hormone (GHRH) stimulates GH release

          > triggered by low blood GH or glucose, or high amino acid levels

        • Growth hormone-inhibiting hormones (GHIH) somatostatin) inhibits release

          >triggered by increase in GH and iGF levels

      • Ghrelin (hunger hormone) also stimulates GH release

Homeostatic Imbalance:

  • hypersecretion of GH is usually caused by anterior pituitary tumor

    • in children results in gigantism

      • can reach heights of 8 feets

    • in adults results in acromegaly

      • overgrowth of hands, feet, and face

  • Hyposecretion of GH

    • in children results in pituitary dwarfism

      • may reach heights of only 4 feet

    • in adults usually cause no problem