The Endocrine System

Relevance of the Endocrine System• Recall nervous system:

– Control is largely “instant” and “transient”

• Only exerts control over target organ while action potentials & neurotransmitter is released

• Must directly innnervate that organ (must have synapses within the target organ)

• Once neurotransmitter release has halted, organ usually returns to “normal” or “unstimulated” state

Relevance of the Endocrine System• Endocrine system allows nervous system to

control over longer periods– Endocrine effects usually long-lasting

– Normally requires less of the “signal compound” or hormone to stimulate compared to neurotransmission

– Allows 1 endocrine organ in a central location to influence/stimulate many other organs without direct contact

• Endocrine system uses BLOOD to deliver the signal– Can have a very DIVERSE target (broad delivery pattern)

– Nervous system is very specific…uses neurons to deliver the signal…very precise targeting

Endocrine System Features• Endocrine glands vs. exocrine glands:

– Endocrine = no ducts, secrete directly into the bloodstream

• Hormones are rarely secreted into sweat or ear wax

– Exocrine = ducts, secrete to the exterior of the body• Mucus, sweat, oil, ear wax etc.

• Endocrine signals (hormones) are generally proteins or modified “lipids” – Recall neurotransmitters: single modified amino acids

or small peptides– Hormones generally larger:

• Proteins (10-1000 amino acids long)• Modified lipids (cholesterol)

Endocrine System Features• Recall nervous system = very quick effects

– Stimulus-CNS-response

– Effects are only during neurotransmitter release

• Endocrine effects usually much slower– Stimulus-CNS-response-hormone release….

– Effects much longer-lasting due to the method by which hormones influence their target cells

Endocrine System Features• Hormones require the presence of a specific

hormone receptor– Similar to a neurotransmitter receptor (binds a specific

protein rather than neurotransmitter)

– Receptor does not act as an ion channel (unlike neurotransmitter receptor)

• Instead, hormone receptors use chemical modifications within the cytoplasm

– “second messenger”

– Phosphorylation

– “dimerization”

• All of these chemical modifications require time, energy etc.

Endocrine System Features• Key point:

– Like neurotransmitter receptors, unless the target cell expresses the specific hormone receptor, it will not “sense” anything, and will not respond

• Without the specific hormone receptor, target cells cannot respond to the presence of a hormone

– Recall that hormones are secreted into blood: • Not very much “specific targeting” when it comes to delivery

(practically every cell in your body will have access to the hormone once it enters the blood)

• Specificity requires the target cell to have already expressed the particular receptor for that hormone

Endocrine System Features• Recall the types of hormones:

– Protein: requires a cell-surface receptor• Once bound to a hormone, these receptors undergo chemical

changes that result in changes within the cytoplasm– “second messenger” in your book

– Modified lipids (cholesterol…steroid hormones)• Fat-soluble (lipds) hormones can cross the plasma membrane

without an external receptor– Bind to cytoplasmic receptors INSIDE the cell rather than on the

surface

– Trigger similar “second messenger” signal “pathway” within the cell

Endocrine System Features• Confusion: from the schematic,

you’d think that ALL hormones trigger cyclic adenosine monophosphate (cAMP) production.– cAMP is only 1 of many “second

messengers” within a cell– If cAMP were the ONLY second

messenger, ALL hormones would elicit the SAME effects

– Other second messengers = cGMP, chemical alterations of plasma membrane lipids, phosphorylation of various proteins within the cell etc.

Endocrine System Features• Confusion: in this schematic for

steroid hormones (modified lipid hormones), it would appear that no second messengers are utilized (in this case, no indication of cAMP)– This is also too “simplified”: the

cytoplasmic receptors can trigger chemical changes within the cell similar to “second messengers”

First & Second Messengers• The “First messenger” = hormone itself

– Usually doesn’t have to enter the cytoplasm– Receptor-hormone binding triggers chemical

changes within the cell• These chemical changes (cytoplasmic signals

through chemical modifications) = “second messenger”

– Hormone does not have to enter the cytoplasm in order to elicit these effects

Second Messengers• Whole field of biochemistry & molecular

biology devoted studying “signal transduction”– What signals are used for particular receptors

• Endocrine, stress etc. all use signal transduction pathways

– Series of chemical reactions within the cell that are SPECIFIC for each receptor

• These different signal transduction pathways are what give hormones their “specificity” WITHIN the cell

Second Messengers ??????• Example: 4 different hormones

– 3 are proteins (water soluble)– 1 is a modified lipid (steroid)– All 4 have different receptors

• However, all 4 receptors can elicit cAMP activity (for argument’s sake)

• HOW do these 4 different receptors stimulate the cell to do completely different things?

– Different signal transduction pathways AFTER receptor-ligand binding…the cAMP activity might stimulate completely different effects, despite using the same second messenger

» Imagine trying to chase down all the possible chemical pathways!!!! (it can get overwhelming)

Second Messengers ??????• Remember how acetylcholine (neurotransmitter)

and epinephrine (neurotransmitter) can have opposite effects in some tissues?– Both are generally “stimulatory”, however, in

some tissues, these neurotransmitters are inhibitory (reduce activity)

• Similar concept to different hormone receptors– 1 hormone can elicit different effects in

different cells if their “second messenger” signal transduction pathways are different

Feedback Control• Many hormones rely on feedback for secretory

control– Once they elicit their effects, the target cells

can feed back signals to the origin and reduce hormone secretion

• Alternatively, once hormone levels reach a particular concentration in the blood, the endocrine organ halts secretion

• “Negative feedback” (acts to limit; most common feedback control mechanism)

– “Positive feedback” = stimulation of the target organ/cell triggers MORE hormone release

• Often seen during parturition & breast feeding

Endocrine organs• Can be divided into 2 groups:

– Cranial• Within the skull

– Hypothalamus– Pituitary gland– Pineal gland

– Extracranial• Outside the skull

– Thyroid gland– Parathyroid gland– Thymus– Pancreas– Adrenals– Gonads

Hypothalamus• Recall regions of the brain

– Hypothalamus = below the thalamus– Very small region, forms the “third ventricle” – Controls the pituitary gland

Hypothalamus• Secretes number of hormones that control

pituitary gland:– “releasing” and “inhibiting” hormones that act

on the pituitary gland• Tell the gland to “release” a hormone, or “stop

releasing”

– Also produces a number of hormones that are transported into the pituitary to other specialized “storage” cells

• These cells will release the hypothalamus-produced hormones upon neural commands from the hypothalamus itself

Green = hormones produced in the hypothalamus that are transported into the posterior pituitary gland

Purple= hormones produced in the anterior pituitary that are only released upon the correct hormone signal from the hypothalamus

Pituitary gland• Sometimes mistakenly called “master

endocrine gland”– Remember that the pituitary gland will NOT

release anything unless it receives input from the hypothalamus

• Two distinct regions of the pituitary gland: – Posterior (neurohypophysis)

• Under neural control

– Anterior (adenohypophysis)• Under hormone control

Pituitary gland• Two distinct regions of the pituitary gland:

– Posterior (neurohypophysis)– Anterior (adenohypophysis)

• Remember the hypothalamus:– Releases “control” hormones to the anterior

pituitary gland• Anterior pituitary then releases or stops releasing

the corresponding hormone

– This system relies on a distinct blood flow/vessel system = portal blood system

Portal System• In order to directly control the pituitary, the

hypothalamus blood vessels are joined to the pituitary blood vessels in a “portal system”– Veins from the hypothalamus (where the

hypothalamic hormones are released into) merge with capillaries that feed into the anterior pituitary

• Carries oxygen-rich blood to pituitary, along with the “control” hormones from the hypothalamus

– Normally artery-capillary-vein-heart

– Portal system = artery-capillaryA-vein-capillaryB-vein-heart

Pituitary hormones

• Anterior lobe (adenohypophysis) hormones– Growth hormone

– Thyrotrophin (stimulates thyroid…another endocrine organ)

– Adrenocorticotrophic hormone (stimulates adrenals…another endocrine hormone)

– Follicle stimulating hormone (FSH…stimulates gonads)

– Lutenizing hormone (with FSH, triggers ovulation & sperm production)

– Prolactin (for breastmilk production)

– Melanocyte stimulating hormone (skin tone)

Pituitary Hormones• Posterior lobe (neurohypophysis)

– Oxytocin: actually made in hypothalamus, transported down to posterior pituitary

• Triggers labor contractions

• Stimulates mammary glands to produce milk

– Anti-diuretic hormone (vasopressin)• Also made in hypothalamus & stored in posterior

pituitary

• Reduces H2O loss from renals (reduces water loss)

Pineal Gland• Located behind/posterior to the thalamus,

above cerebellum– Larger in children than adults

• Secretes melatonin: involved in circadian rhythm

Thyroid

• Located in neck (surrounds trachea)– Largest endocrine gland– Heavily reliant on iodine

• Thyroxine: increase protein synthesis, increase carbohydrate metabolism

• Tri-iodo-thyronine: more potent than thyroxine

• Calcitonin: decrease blood calcium through inhibition of osteoclast activity

Parathyroid

• Parathyroid gland(s)– Behind/posterior to the thyroid gland (para =

around)– 4 distinct glands– Secretes parathyroid hormone: increase blood

calcium concentration• Increase osteoclast activity

• Antagonizes calcitonin

Adrenal Glands

• On superior edge of both kidneys

• 2 portions:

– Outer cortex (adrenal cortex)• bulk of the adrenal gland

– Inner medulla (adrenal medulla)• Produce adrenaline & norepinephrine

(catecholamines)• Increase cardiac output, dilate blood vessels,

increase mental alertness, increase metabolic rate

Adrenal Glands• Outer cortex (bulk of the adrenal gland)

– Mineralcorticoids (mineral-targeting hormones from the cortex)

• Controls electrolyte homeostasis (influences aldosterone…works on kidneys to control sodium and potassium losses)

– Glucocorticoids (glucose-metabolism hormones from the cortex)

• Controls metabolic rate, inflammation, vasoconstrictoin

– Gonadocorticoids (gonad-targeting hormones from the cortex)

• Estrogen & testosterone

Pancreas

• Has BOTH endocrine & exocrine functions

– Endocrine = blood-glucose regulation• Glucagon: acts to increase blood glucose through

gluconeolysis (liver digestion of glycogen stores)– From alpha cells of the endocrine pancreas

• Insulin: acts to decrease blood glucose through gluconeogenesis (liver & skeletal muscle polymerization of glycogen from glucose)

– From beta cells of the endocrine pancreas

Gonads (sex/reproductive organs)

• Testes & ovaries

– “mixed glands” (make both sex hormones & sex cells)• Testes: testosterone made by interstitial cells

– Controls sex organ development

• Ovaries: follicles produce estrogens– Corpus luteum also produces progesterone (for

pregnancy)

Thymus

• Larger in children than adults– Associated heavily with the lymphatic system (“T-

cell” = thymus-dependent cell)– Produces thymosin: influences T-cells following

exit from the thymus

Endocrine pathophysiology• Endocrinology often quite challenging

– Hormones are very specific (target specific receptors on specific cells)

– Responses are often linked (often 4-5 hormones can elicit similar “whole body” effects)

– Often linked to metabolic disorders• Have to treat metabolic condition first, endocrine issue

follows

– Often diagnosed via blood tests• Radioimmunoassays (check for hormone concentration)• Cholesterol tests (assess metabolic function)• Iodine (assess thyroid function)

Endocrine pathophysiology• Pituitary pathophysiology

– Panhypopituitarism: reduced pituitary activity or total loss of pituitary function

• Decreased sex organ function

• Supplement with exogenous hormones

– Abnormal growth hormone: • Inadequate during childhood = pituitary dwarfism

• Inadequate during adulthood = Simmond’s disease– Premature aging

• Oversecretion during childhood = gigantism

• Oversecretion during adulthood = acromegaly– Bones thicken, soft tissues grow inappropriately

Acromegaly Gigantism

Occurs during adulthood Begins during childhood

Endocrine pathophysiology• Pituitary pathophysiology

– Inadequate anti-diuretic hormone secretion• Diabetes insipidus (polyurea…excess urination; ionic

imbalances secondary to excess urine production)

Endocrine pathophysiology• Thyroid & parathyroid pathophysiology

– Hypothyroidism• During childhood = cretinism (“cretins”)

– Child starts normally due to thyroxine from mother

– Treat with exogenous thyroxine

• During adulthood = myxedema– Edema throughout the body, increased blood pressure

– Goiter (abnormal thyroid growth)• Endemic = inadequate iodine intake

• Grave’s disease = autoimmune disease; antibodies act as thyroid stimulating hormone to stimulate inappropriate thyroid growth

MyxedemaCretinism

Endemic goiter Grave’s disease

Endocrine pathophysiology• Pancreatic pathophysiology

– Diabetes mellitus• Type I diabetes: insulin dependent due to autoimmune

destruction of pancreatic beta cells (loss of insulin production)

• Type II diabetes: insulin insensitive due to reduced responsiveness to insulin (metabolic obesity)

– Reactive hypoglycemia (usually coupled with Type II diabetes)

• Carbohydrates trigger excessive insulin response = post-prandial hypoglycemia

Endocrine pathophysiology• Adrenal pathophysiology

– Pheochromatocytomas: chromaffin cell tumor• Excessive norepinephrine secretion = resembles ANS

overstimulation

– Addison’s disease: decreased mineralcorticoid & glucocorticoid secretion

• Constant hypoglycemia, electrolyte imbalances

– Cushing’s syndrome: increased glucocorticoid secretion (Zona fasciculata)

• Altered metabolism and physical changes indicative of edema

Pediatric Cushing’s syndrome