Human Phys Exam 3

Endocrinology

secretion of hormones from endocrine glands into the circulation, and the action of those hormones on target tissues which have receptors for specific hormones

broadcast signal to distant tissues

exocrine

secretions outside of the body (e.g. sweat glands)

endocrine

secretion into the blood, acting on distant tissues

paracrine

secretion acting on nearby cells

autocrine

acting on the same cell

glands

exocrine and endocrine cells that secrete chemicals

adipose tissue

major hormone: leptin

primary target organ: hypothalamus

primary effect: suppresses appetite

adrenal cortex

major hormones: glucocorticoids, aldosterone

primary target organs: liver, muscles, and kidney

primary effects: glucocorticoids influence glucose metabolism; aldosterone promotes Na+ retention, K+ excretion

adrenal medulla

major hormones: epinephrine

primary target organs: heart, bronchioles, and blood vessels

primary effects: causes adrenergic stimulation

hypothalamus

major hormones: releasing and inhibiting hormones

primary target organs: anterior pituitary

primary effects: regulates secretion of anterior pituitary hormones

pituitary, anterior

major hormones: trophic hormones

primary target organs: endocrine glands and other organs

primary effects: stimulates growth and development of target organs; stimulates secretion of other hormones

thyroid gland

major hormones: thyroxine (T₄) and triiodothyroxine (T₃); calcitonin

primary target organs: most organs

primary effects: T₄ and T₃ promote growth and development and stimulate basal rate of cell respiration (basal metabolic rate BMR); calcitonin may participate in the regulation of blood or Ca²⁺ levels

How to prove that abnormal loss of a hormone causes a disease

connect the circulatory systems of a normal and diseased individual

leptin

~100 amino acid peptide hormone secreted by adipose tissue into the blood

ob/ob mutation

• extra stop codon terminates leptin transcript (missing hormone supplied by wildtype mouse)

• hypoleptinemia

• no leptin hormone, so can’t produce negative feedback signal and keeps putting on fat

db/db mutation

• extra stop codon terminates leptin receptor (missing receptor)

• functional hypoleptinemia

• no leptin receptors, so can’t detect negative feedback signal, and keeps putting on fat

feedback regulation

high levels of regulated variable cause hypothalamus to downregulate behavior & physiology that drive the variable up

hormone types

• nuclear receptor hormones (steroids, thyroid hormone, and retinoic acid)

• polypeptide and glycoprotein hormones (second-messenger coupled hormones)

  • GPCR lined to cAMP

  • GPCR linked to phospolipase C and Ca++

  • tyrosine kinase receptors

nuclear receptor hormones

1. lipophilic molecules that pass through membranes (and skin)

2. coordinate peripheral physiological and central neural response

3. release regulated by synthesis

4. bind to cytoplasmic/nuclear receptors

5. receptors bind to DNA, affecting gene transcription

estrogen receptor

in the presence of estrogen binds to estrogen response element

polypeptide and glycoprotein hormones

• small peptides

• coded for by genes, processed in ER & Golgi, packaged in vesicles and secreted by endocytosis

• hydrophilic molecules so soluble in blood; circulate and act on plasma membrane receptors to induce second messenger signaling in the target cells

common hormone receptor signaling pathways

• GPCR linked to cAMP

• CPCR lined to phospholipase C and Ca++

• tyrosine kinase receptors

cAMP as a second messenger

1. hormone binds to receptor on target cell’s plasma membrane

2. hormone-receptor interaction acts by G-proteins to stimulate adenylate cyclase on the cytoplasmic side of the membrane

3. activated adenylate cyclase catalyzes conversion of ATP to cyclic AMP (cAMP) in the cytoplasm

4. cyclic AMP activates protein kinase enzymes in the cytoplasm

5. activated cAMP-dependent protein kinase phosphorylates (transfers phosphate groups) to activate/inactivate other enzymes in the cell

6. enzyme activity mediates the target cell’s response to the hormone

intracellular Ca++ as a second messenger

1. hormone binds to receptor on target cell’s plasma membrane

2. hormone-receptor interaction acts by G-proteins to stimulate phospholipase C enzyme in the membrane

3. activated phospholipase C catalyzes the conversion of phospholipids in the membrane to inositol triphospate (IP3) and diaclyglycerol (DAG)

4. IP3 enters the cytoplasm and diffuses the endoplasmic reticulum, binds to IP3 receptors, and causes Ca++ channels to open

5. Endoplasmic reticulum has high [Ca++], Ca++ rushes out of ER into cytoplasm

6. Ca++ in the cytoplasm binds to calmodulin protein

7. activated calmodulin activates protein kinases, which phosphorylate (transfers phosphate groups) to activate/inhibit other enzymes in the cell

8. Enzyme activity mediates the target cell’s response to the hormone

tyrosine receptor kinases

1. hormone binds to receptor on target cell’s plasma membrane

2. receptors dimerize

3. receptors phosphorylate each other (the receptors themselves are kinases)

4. activated receptors phosphorylate target proteins (“tyrosine kinases” because add phosphate groups to tyrosine residues in target proteins)

5. phosphorylated proteins activate/inhibit other pathways in the cell

6. enzyme activity mediates the target cell’s response to the hormone

hypothalamus (description)

the brain region between brainstem and cerebrum that integrates sensory information and generates physiological responses to maintain homeostasis

pituitary gland (description)

attached to the underside of the hypothalamus by the infundibulum.

hypothalamus is connected to the pituitary by the hypothalamo-hypophyseal portal veins that carry releasing hormones to the anterior pituitary, and by the hypothalamo-hypophyseal tract of axons projecting to the posterior pituitary

anterior lobe (description)

contains endocrine cells that secrete tropic hormones into the circulation that stimulate target organs in the body

posterior lobe (description)

contains axon terminals of ADH and oxytocin neurons that originate in the hypothalamus; releases ADH (water retention) and oxytocin (uterine contractions, milk release) into the bloodstream

how does the hypothalamus regulate pituitary function

releasing and inhibiting hormones

releasing hormones

→ pituitary to cause release of stimulatory hormones → increase target glands activity

inhibitory hormones

→ pituitary to suppress release of stimulatory hormones → decrease target gland activity

result of transcection of infundibulum

→ decrease of all pituitary hormones except prolactin increases

hypothalamic pituitary axes

• HPA

• HPG

• HPT

target hormones

→ provide negative feedback to hypothalamus and pituitary → decreased of releasing hormones and stimulatory hormones

tropic hormone

pituitary → target gland

HPA axis

hypothalamus: corticotropin-releasing hormone (CRH)

anterior pituitary: adrenocorticotropic hormone (ACTH)

target organ: adrenal cortex

function: stimulate corticosteroid synthesis (stress)

HPG axis

hypothalamus: gonadotropin-releasing hormone (GnRH)

anterior pituitary: lutenizing hormone (LH)

target organs: ovaries & testes

function: stimulate estrogen & testosterone synthesis (reproduction)

HPT axis

hypothalamus: thyrotropin-releasing hormon (TRH)

anterior pituitary: thyroid-stimulating hormone (TSH)

target organ: thyroid gland

function: stimulate thyroxine synthesis (metabolism)

hypothalamic-pituitary pathologies

• hypersecretion due to

  • tumors

  • lack of negative feedback

  • inappropriate synthesis/degradation

• real or functional hyposecretion due to

  • lack of releasing/tropic hormones

  • lack of synthetic enzymes

  • lack of receptors

glucocorticoids (cortisol)

mediate long-term transcriptional stress response

convert protein and fat to glucose suppress immune system

mineralocorticoids (aldosterone)

retention of Na+ and H2O by kidneys increased blood volume and pressure

adrenal cortex

secretes mineralocorticoids (aldosterone)

actions of glucocorticoids (GCs)

• containment of stress response

• suppression of swelling, suppression of immune system → reduce tissue damage

• mobilization of energy from muscle and fat

• induce liver enzymes for detoxification

• suppression of “optional” activities: reproduction, growth

• adaptive in low doses, but problematic at high or chronic doses

dexamethasone suppression test

administers an artificial glucocorticoid to confirm that HPA responds to negative feedback

pathologies of HPA

• defects in cortisol synthetic enzymes

• Addison’s disease

• tumors

• pheochromacytoma

• Cushing’s syndrome: elevated cortisol