PHYSIO FINAL: Endocrine

What is the general overview of endocrine function?

• Endocrine system acts with nervous system to coordinate and integrate activity of body cells

• Communicates to receptors target cells via hormones

• Slower response than CNS, but longer response

Hormones

Chemicals secreted into the blood

• Released by endocrine glands

A major difference between neurotransmitters and hormones?

Hormones reach their destination via the blood

How does the endocrine system function?

• Stimulus acts on glands

• Glands increase or decrease output of hormones

• Hormones act on receptor on target cell

• Target cell leads to response

Endocrine glands

• Pituitary

• Hypothalamus (neuroendocrine)

• Thyroid

• Parathyroid

• Adrenal

• Pineal

• Exocrine (Pancreas, gonads)

How do hormones act only on their target cells?

• Hormone binds to target cells via specific receptors

• Receptors can be on the surface of the cell or inside

What are the two classes of hormones?

• Lipid soluble (hydrophobic)

• Water soluble (lipid insoluble, hydrophilic)

How do lipid soluble hormones act?

• Pass/diffuses through cell membrane and bind to intracellular receptors

• Forms receptor complex, enters nucleus, binds to DNA, initiates protein synthesis

  • Steroid hormones (derivatives of cholesterol)

    • Testosterone, estradiol, cortisol

How do water soluble hormones act?

• Bind to G-protein coupled receptors in/on cell membrane

• Act via second messenger pathway

• Hormones binds to receptor, which activates G protein, which activates second messengers, which triggers response of target cell

  • Amino acid-based hormones (Except thyroid hormone)

    • Epinephrine, norepinephrine

  • Peptide/protein hormones

    • Growth hormone, ADH, insulin, FSH, oxytocin

The ability of a target cell to respond to a particular hormone depends on which 4 mechanisms?

• Levels of the hormone in the blood

• Affinity of binging between receptor and hormone

  • High or low

• Relative number of receptors on/in target cells

• Influences by other hormones

What are the three mechanisms that control hormone release?

• Nervous system stimulation

• Humoral stimuli (chemical changes in blood)

• Hormonal stimulation

Nervous system stimulation

• Sympathetic fibers fire onto adrenal medulla

• Epinephrine and norepinephrine is released into blood

Humoral Stimuli

• Chemical changes in blood

  • Ex. levels of critical ions or nutrients

What controls the release of pituitary hormones?

Hypothalamic hormones

Tropic Hormones

Hormones that affect secretion of another hormone

Affinity

Measure of strength of attraction between a receptor and its ligand

• The higher the attraction, the higher the affinity

• Ex. Norepinephrine has a higher affinity for alpha 2 receptors than epinephrine

Down-regulation

High hormone levels leads to loss of receptors

Up-regulation

Low hormone levels leads to increased number of receptors

Permissiveness

In order for a hormone to have its full response, another hormone must be present in adequate amounts

Synergism

Combined effect of several hormones is greater than sum of separate effects

Antagonism

One hormone reduces the effectiveness of another hormone

What are the two parts of the pituitary gland?

• Paraventricular nucleus

• Supraoptic nucleus

How does the hypothalamus connect to the posterior pituitary?

Paraventricular nucleus

How does the hypothalamus connect to the anterior pituitary?

Supraoptic nucleus

What hormones are released by the posterior pituitary?

• Oxytocin and ADH (stored in axon terminals)

• When hypothalamic neurons fire, they are released

• Travel to their sites of action via blood

What is oxytocin?

• Peptide (lipid insoluble)

• Target organ and effects

  • Uterus → contractions

  • Breasts → milk ejection

What is oxytocin stimulated by?

• Cervical stretching

• Suckling of infant at breast

What is oxytocin inhibited by?

Lack of stimuli

What is Antidiuretic hormone (ADH)?

• Peptide (lipid insoluble)

• Target organ and effects

  • Kidneys → water reabsorption → increased blood volume

What is ADH stimulated by?

Decreased blood volume

What is ADH inhibited by?

Adequate hydration, Alcohol

What does ADH deficiency or Lack of kidney response lead to?

• Diabetes insipidus

• Not related to T1 or T2 diabetes

• Results in:

  • Frequent urination

  • Excessive thirst

How is the anterior pituitary vascularly connected to the hypothalamus?

The hypophyseal portal system

• Primary capillary plexus

• Hypophyseal portal veins

• Secondary capillary plexus

How is the release of anterior pituitary hormones triggered?

Hypothalamic hormones travel through portal system, to anterior pituitary, which triggers release of anterior pituitary hormone

What does anterior pituitary hormone act on?

• Target organs OR triggers release of hormones from endocrine glands

• Endocrine hormone acts on targets and often exerts negative feedback on hypothalamic and anterior hormones which triggered its release

What is growth hormone secreted by?

Anterior pituitary

What regulates the release of GH?

Hypothalamic hormones

• GHRH and GHIH

Targets of GH

Many:

• Muscle

• Bone

• Cartilage

• Soft tissues

Effects of GH

• Metabolic effects

• Growth-promoting effects

Metabolic effects of GH

• GH binds to receptors on targets

• Increased GH leads to:

  • Increased lipolysis in adipose tissues → increased fatty acids in blood

  • Increased glycogenlysis in liver → increased blood glucose levels

Growth-promoting effects of GH

• Indirect effect

• Stimulates liver, skeletal muscle, cartilage, and bone to secrete hormones called Insulin-like Growth Factors (IGFs) into blood

• IGFs have growth promoting effects

IGFs

• Main Targets: Muscle, bone, cartilage, soft tissues

• Protein synthesis in skeletal muscle

• Lengthening of long bones (femur, humerus, etc.)

• Increased mitosis (growth) in soft tissues

GHRH

• Growth hormone-releasing hormone

  • triggered by low blood GH or glucose

GHIH

• Growth hormone-inhibiting hormone

  • triggered by increase in GH and IGF levels

Effect of increased GH and IGF levels

• Inhibit GHRH release

• Stimulate GHIH release

• Affect on GH: Decreased GH synthesis and release

Abnormalities in GH secretion

• GH excess pre-puberty → gigantism

• GH excess post-puberty → acromegaly

• GH deficiency pre-puberty → pituitary dwarfism

Where is the thyroid located?

Just below larynx

• Consists of follicles: follicular cells + colloid fluids

What do follicular cells produce?

Thyroid hormones

What do parafollicular cells produce?

Calcitonin

What is thyroid hormone?

Body’s major metabolic hormone

What are the two forms of thyroid hormone?

• T4 (Thyroxine) - Two tyrosine molecules with four bound iodine atoms

• T3 (Triiodothyronine) - Two tyrosine molecules with three bound iodine atoms

How is TH synthesized?

• Tyrosine is synthesized and released into lumen of follicles

• Iodine is attached to tyrosine

• Iodine-tyrosine complex linked → T3 or T4