The Endocrine System

I. Overview

• Two major controlling systems in the body : nervous and endocrine.
• Nervous system regulates the activity of muscle and glands by means of electrochemical impulses delivered by neurons.
• The endocrine system influences the metabolic activities of cells by means of hormones (chemical messengers).
• The endocrine glands are ductless glands and include pituitary, thyroid, parathyroid, adrenal, pineal, and thymus.
  
• Organs (Diagram) that contain endocrine tissue include the pancreas, gonads (testes and ovaries) and digestive organs (stomach and intestines, enteroendricine tissue).
• Pituitary secretions regulated by neuroendocrine gland, the hypothalamus.

II. Hormones

• Hormones - chemical substances secreted by cells into the extracellular fluids and regulate the metabolic function of other cells in the body
• Two chemical classes: Diagram
  
  • Amino acid based - protein, peptide, and catecholamines (epinephrine and norepinephrine)
  • Steroids - most hormones synthesized from cholesterol (but some may be derived from linoleic acid and arachidonic acid)
    

A. Hormone-Target Cell Specificity

• Hormone is received by a target cell and evokes a response
• Cell response is dependent upon protein receptors on the plasma membrane or receptors in the nucleus and if receptors present, will bind hormones complimentarily
• Extent of target-cell activation (response) by hormone-receptor interaction depends on....
  1. blood levels of the hormone
  2. relative numbers of receptors for the specific hormone
  3. affinity for the hormone by receptor
• Regulation of cell receptors:
  • Up regulation - increase in the number of receptors with increase in hormone concentration
  • Down regulation - prolonged exposure, cells become desensitized and there is a loss of receptors

B. Mechanism of Hormone Action

1. A hormonal stimulus typically produces one or more of the following changes:
   1. changes in plasma membrane permeability and/or electrical state (membrane potential)
   2. synthesis of proteins or certain regulatory molecules (such as enzymes) within the cell
   3. enzyme regulation (activation or deactivation)
   4. induce secretion
   5. stimulation of mitosis
2. Two major mechanisms leading to hormone action: 
   1. Second messenger systems (mediate the target cell's response to hormone) Diagram
      • Hormone binds to a receptor on the cell membrane
      • Receptor causes adenylate cyclase in the membrane to be active and convert ATP into cAMP
      • cAMP activates protein kinases
      • Protein kinases activates enzymes, stimulate cellular secretion, opens ion channels, etc.....
   2. Direct gene activation Diagram
      • Steroid hormones diffuse easily into their target cells
      • They bind to receptors within the nucleus
      • The activated complex then interacts with the nuclear chromatin binding to a receptor protein
      • Binding to chromatin "turns on" DNA Transcription of mRNA which is used to direct the synthesis of other proteins (e.g. enzymes).

C. Control of Hormone Release

• Synthesis and release of most hormones are regulated by some type of negative feedback Diagram
• The output of the system feeds back and decreases the input into the system
• Three types of stimuli that initiates/stimulates the manufacture and release of hormones:
  1. Hormonal - hypothalamus produces releasing and inhibiting hormones Diagram
     
  2. Humoral - changing in blood levels of ions and nutrients
  3. Neural - neuronal control (e.g. sympathetic nervous system release of catecholamines during stress)

III. Endocrine Organs of the Body

A. Pituitary Gland (Hypophysis) Diagram

• Housed in the sella turcica of the sphenoid bone
• Pituitary is connected the hypothalamus by the infundibulum and is divided into two lobes:
  • posterior lobe (neurohypophysis) - neuroglia and nerve fibers release neurohormones premade from hypothalamus
  • anterior lobe (adenohypophysis) - glandular tissue
• Structures:
  • posterior lobe - infundibulum and pars nervosa
  • anterior lobe - pars tuberalis (superior portion) and pars distalis (inferior portion)
• Pituitary-Hypothalamic Relationships Diagram
  
  • Neurohypophysis Diagram
    • Connected with hypothalamus via a nerve bundle (hypothalamic-hypophyseal tract) which runs through the infundibulum
    • The tract arises from neurons in the supraoptic (releases hormone ADH) and paraventricular (releases hormone oxytocin) nuclei of the hypothalamus. 
  • Adenohypophysis Diagram
    • No neural connection, rather vascular connection
    • Primary capillary plexus communicates with the secondary capillary plexus via hypophyseal portal veins within the infundibulum
    • Primary and secondary plexus and hypophyseal portal vein are collectively called the hypophseal portal system which secretes releasing and inhibiting hormones from neurons in the ventral hypothalamus.
    • Adenohypophyseal hormones (all are secon messenger hormones) - six distinct adenohypophyseal hormones:
      • (GH) - growth hormone
      • (PRL) - prolactin 
      • Tropic (regulates the hormone function of other endocrine glands)
        • (TSH) - thyroid-stimulating
        • (ACTH) - adrenocorticotropic
        • gonadotropic (regulate thefunction of gonads)
          • (FSH) - follicle-stimulating
          • (LH) - luteinizing

B. Thyroid Gland Diagram

• Butterfly-shaped and largest endocrine gland located in the anterior neck overlying the trachea just inferior to the larynx.
• The thyroid gland has two lateral lobes connected by a medial tissue mass called the isthmus.
• Thyroid gland composed of follicles which are concentric rings of cells with a lumen.
• The walls of each follicle formed largely by cuboidal epithelial cells which produce the glycoprotein thyroglobulin.
• Iodinated thyroglobulin is used to synthesize two thyroid hormones (thyroxin and triodothyronine) which are collectively called thyroid hormone.
• Thyroxine (T4) and triodothyronine (T3) - thyroid hormone stimulates enzymes concerned with glucose oxidation and therefore increases basal metabolic rates and heat production (calorigenic effect)
• Synthesis of thyroid hormone: Diagram
  • Thyroglobulin synthesis - TSH is secreted and sent to follicle cells in the thyroid. Thyroglobulin is synthesized on ribosomes and sent to golgi where sugar residues are attached. Thyroglobulin is then packed into vesicle, transported to the apex of the cell, and discharged into the lumen of the follicle.
  • Iodine attachment - cells accumulate iodides and convert them to iodine which attach to tyrosine aminoacids of thyroglobulin (results in monoiodotyrosines, MIT, and diiodotyrosines, DIT). Enzymes link iodotyrosines: MIT + DIT = T3 and DIT + DIT = T4. Hormones are still part of the colloid and need to be cleaved to be released.
  • Hormone Cleavage - follicle cells reclaim iodinated thyroglobulin by endocytosis and packaged in lysosomes - lysosomal enzymes cleave T3 and T4 which diffuse into the blood stream.
  • NOTE: some T4 is converted to T3 before secretion BUT most T3 is generated in the peripheral tissues
• T3 and T4 are second messenger hormones
• Calcitonin (thyrocalcitonin) - polypeptide hormone produced by the parafollicular (C cells) cells of the thyroid gland. Calcitonin lowers blood calcium and phosphate levels and is a direct antagonist of parathyroid hormone.

C. Parathyroid Diagram Diagram

• Embedded on the posterior surface of the lobes of the thyroid gland (usually four).
• Secretes parathyroid hormone (PTH)/parathormone
• PTH controls the calcium balance of the blood and is triggered by increased calcium levels or inhibitd by hypercalcemia
• PTH stimulates three target organs: skeleton, kidneys, and intestines.
• PTH release results in...
  1. Activation of osteoclasts to digest bony matrix and release calcium ions and phosphate
  2. Enhanced resorption of calcium ions
  3. Increased absorption of calcium by intestinal mucosal cells

D. Adrenal Gland (Suprarenal) Diagram

• Pyramid-shaped organs located at superior border of each kidney and is surrounded by connective tissue and embedded in fat
• There two separate portions: inner medulla and an outer cortex.
• Adrenal Cortex
  • Synthesizes steroid hormones (corticosteroids) from cholesterol
  • Cortical cells arranged in three concentric regions:
    • zona glomerulosa - produces mineralcorticoids (Aldosterone) that control the balance of minerals and water
    • zona fasciculata - (linear cords) produce glucocorticoids (cortisol)
    • zona reticularis - produc glucocorticoids (cortisol) and gonadocorticoids (androgens/testosterone)
  • Mineralocorticoids - regulation of electrolyte concentrations in extracellular fluids. 95% of all mineralocorticoids produced is aldosterone which promotes sodium reabsorption from urine in kidneys and regulates some electrolyte concentrations. Four mechanisms involved in regulation of aldosterone secretion:
    • Renin-angiotensin system - juxtaglomerular apparatus (in kidney) releases the enzyme renin in response to decreased blood pressure or decrease in plasma osmolarity. Renin cleaves angiotensinogen which causes an enzymatic cascade leading to the formation of angiotensin II. Angiotensin II stimulates aldosterone release.
    • Sodium and Potassium concentrations- increased potassium and decreased sodium stimulates aldosterone secretion.
    • ACTH - in response to stress, hypothalamus secretes more corticotropin releasing hormone(CRH) which increases ACTH blood levels, thereby increasing aldosterone secretion.
    • Atrial Natiuretic Factor (ANF) - ANF is a hormone secreted by the heart when blood pressure rises (as a result of sodium-water imbalance) and inhibits the renin-angiotensin system.
  • Glucocorticoids - influences metabolism. Its secretion is stimulated by ACTH/CRH. Examples are cortisol (hydrocortisone), cortisone, and corticosterone.
  • Gonadocorticoids - sex hormones, androgens (testosterone), some estrogens and progesterone.
• Adrenal Medulla
  • Contains chromaffin cells arranged in irregular clusters and is stimulated by sympathetic preganglionic fibers
  • Adrenal medulla secretes epinephrine (adrenaline) and norepinephrine (noradrenaline)
  • The catechlolamines secreted increase heart rate and blood pressure (via vasoconstriction).

E. Pancreas Diagram

• Contains acinar cells that produce enzymes that are ducted into the small intestine, therefore is a exocrine gland
• Among the acinar cells are islets of Langerhans that produce pancreatic hormones, therefore endocrine gland
• Cells of islets of Langerhans:
  • Alpha cells - glucagon-synthesizing (hyperglycemic hormone)
  • Beta cells - insulin-synthesizing (hypoglycemic hormone)

F. Gonads

• Produce gonadal sex hormones:
  • Ovaries - estrogens and progesterone
  • Testes - testosterone

G. Pineal Gland Diagram

• Roof of third ventricle within the diencephalon and contains pinealocytes
• Secrete melatonin.
• May be involved in sleep-wake cycle

H. Thymus

• Thymic epithelial cells secrete the peptide hormones thymopoeitin and thymosin used in the development of immunity

• Acromegaly - excessive production of GH (due to tumor production)
• Galactorrhea - production of milk whether needed or not (possibly due to medication or tumors such as prolactinomas)
• Cushing's syndrome - pituitary adenomas increases production of ACTH which causes adrenal gland to increase production of cortisol; manifests as "moon face," "buffalo hump," and striae
  

• Myxedemia - decrease in function of thyroid resulting from TSH and TRH deficits
• Endemic goiter - thyroid gland enlarges as a result of lack of iodine (follicle accumulates unusable colloid)
• Cretinism - genetic deficiency of fetal thyroid gland in infantsGrave's disease - antibodies act against component of follicle cell membrane (decrease secretion of thyroid hormone)
  

• Addisons disease - hyposecretion of glucocorticoids and mineralcorticoids
• Cushing's disease - caused by tumor within adrenal cortex causes increase production of cortisol
  

• Hyperparathyroidism - results from gland tumor, increases blood calcium levels and causes depressed nervous system and kidney stones
• Hypoparathyroidism - results in PTH deficiency and causes increase in excitability of neurons
  

• Diabetes mellitus - two types: Type I (IDDM) - no insulin activity - increase blood glucose levels; Type II (NIDDM) - inadequate amount of insulin or problem with insulin receptors
• Hyperinsulinism - excessive excretion of insulin, results in decreased blood glucose levels, hypoglycemia.