The Endocrine System

1 Topics

• Types of cell signalling

o Four types of cell signalling (major)

o Four types of hormones (major)

• Types of hormones

• Hormone receptors

• Major endocrine glands

• Major hormones

• The hypothalamus and pituitary

• The thyroid gland

• The adrenal gland

• The pancreas / insulin and diabetes

• The pineal gland

• Atrial natriuretic peptide

2 Adrenal Gland

• Nervous System:

o Neural networks / rapid signalling

• Endocrine System

o Endocrine glands secrete hormones that mediate slower, but longer-lasting responses

o Endocrine system functions more as a regulatory than a command system

Secretes hormones that move through blood or extracellular fluid

• Response can be very rapid (e.g. adrenalin)

• Or very slow (e.g. changes in protein synthesis or gene transcription)

• Adrenal gland has two parts:

o Outer cortex

Produces steroid hormones

o Inner medulla

Releases adrenaline

• Part of fight or flight response

• The more cortisol you have, the more rapidly you age

3 Circulating Hormones

• Classic endocrine hormonal response

o Endocrine gland that contains cells which synthesize and secrete hormones

o Hormones diffuse through extracellular fluid and they circulate in the blood

o Move through blood to these target cells and activates their receptors

4 Neurocrine Endocrine Signaling

• Hormones can also originate / move from nerves

o Referred to as neurohormones

• Rather the cell of a gland producing and secreting hormones they have a nerve doing this function

o From the nerve it is transported through extracellular fluid and blood

Hormones acts on target tissues

• Hypothalamus has neurons which produces two hormones:

o ADH

o Oxytocin

o The axons from these cells are found on the nerve terminals (posterior pituitary)

5 Paracrine and Autocrine Signaling

• Paracrine endocrine signalling

o An endocrine releases hormones

o Hormones don’t travel through the blood

Instead they moves through one cell type to another cell type in the extracellular fluid (short distances)

• Autocrine endocrine signalling

o Cell releases hormones

o Hormones feeds back and has an effect on the same cell that released it

• This can occur in nerves

o -e.g. acetylcholine (paracrine manner)

Released and travels to target cell via extracellular fluid

o –e.g. dopamine (autocrine manner)

Released and travels to target receptor on the same cell

• You can often have an autocrine effect on the cell which either inhibits or accelerates the release of the paracrine substance

o –i.e. release hormones that:

Inhibits release of paracrine substance

Accelerates release of paracrine substance

6 Cell Signalling Regulations

• Four major methods of signalling

o Classical endocrine signalling

Release of hormone (from endocrine cell) transported in blood

binds to receptor protein response

o Neuroendocrine (Neurocrine) signalling

Release of hormone from nerve blood receptor response

o Paracrine regulation

Release of hormone diffusion through extracellular fluid

receptor response

o Autocrine regulation

Release of hormone diffusion through extracellular fluid

receptor on the same cell response

7 Types of Hormones: Amines

• Four major types of hormones

o Fatty Acids

o Steroids

o Peptides

o Amines

Tyrosine-based

• Hydrophilic

• -i.e. water loving

Three hormones are referred to as catecholines (contains catechol group and amine group)

• Dopamine

o Neurotransmitter

• Epinephrine

o Hormone

• Norepinephrine

o Either a neurotransmitter or a hormone

Adrenal glands are wrapped around the upper portions of the kidney

• Adrenaline = Epinephrine

o Epi = around

o Nephros = kidney

• Noradrenaline = norepinephrine

Both dopamine and norepinephrine functions as neurotransmitters

• Epinephrine does not

Norepinephrine and epinephrine function as hormones

• Dopamine does not

8 Peptides

• Peptide hormones

o The liver is always producing angiotensinogen (a protein)

o Angiotensinogen angiotensin (a peptide)

• In response to some stimuli (e.g. low blood pressure), kidney produces rennin (enzyme) and releases it into the blood

o Rennin then acts on angiotensinogen and produces angiotensin I

o Angiotensin I circulates through the lung capillaries and kidneys and is

exposed to ACE (enzyme; angiotensin converting enzyme sufficient to know it just as ACE)

o ACE converts angiotensin I to angiotensin II

o Angiotensin II effects blood pressure regulation and osmotic and ion regulation

o Angiotensin II triggers the adrenal cortex to release aldosterone

9 Steroids / Fatty Acids

• All steroids are derivatives of cholesterol

o Progesterone

o Testosterone

o Estradiol

o Aldosterone

o Cortisol

Hydrophobic

Bind receptors within the cell

Transported in the blood via carrier proteins

• Fatty Acids

o Insects use fatty acids as hormones

• From a mammalian point of view there are three main hormones:

o Amines

o Peptides

o Steroids

10 Hormone Receptors: Cell Surface Receptors

• Hormones exert effects either by

o acting on cell surface receptors

hormone coming from the blood diffusing through the extracellular fluid to bind to a receptor

the binding will set in motion a series of reactions

finally we end up with one or more receptor molecules that bring about the response within a cell

o diffusing into the cell and interacting with receptors in the cytosol or nucleus

hormone is released through secretory cell intro the extracellular fluid and blood

hormone circulates through the blood and then binds to a receptor cell

binding hormone to receptor causes several pathways:

• the production of an effector molecule in cytoplasm

• the production of an effector molecule that moves into nucleus and alters transcription

• Common effector molecules in the cytoplasm:

o Kinase (adds phosphates)

o Phosphatase (removes phosphates)

o Brings about a response within proteins and enzymes

• Enzymes that are either activated or deactivated occur through phosphorylation / dephosphorylation

• A large majority of secondary messengers that leads to effector molecules is through phosphorylation / dephosphorylation

11 Intracellular Receptors

• We can also have hormone receptors inside cells

o In the cytoplasm

Diffuses across the plasma membrane instead of binding to a surface receptor

• Binds to a receptor in the cytosol

o reception

Receptor hormone complex moves into nucleus and triggers a response

• transduction

Affects gene transcription

• response

o In the nucleus

Diffuses across membrane into cytosol into nucleus binds in nucleus

Receptor hormone complex binds with dna to alter gene transcription

12 Aldosterone

• Example of intracellular receptor:

o Aldosterone

Released by outer regions of adrenal glands

• Occurs when [Na+] falls in body fluids

• Angiotensin II causes this release

• High plasma [K+]

Outer regions of adrenal glands release Aldosterone

• Aldosterone moves into the cell and binds to a receptor

• Receptor-hormone complex moves within the nucleus and alters gene transcription

• Increases in transcription will lead to increase in protein synthesis

• Increase in production of sodium channels

• Sodium channel can get inserted in the plasma membrane

13 Function of Aldosterone

• Aldosterone occurs in kidney tubule cells (pre-urine)

• In response to angiotensin II and high plasma/low sodium the adrenal cortex releases Aldosterone

o Aldosterone moves into the cell and interacts with the receptor

o Effect of Aldosterone synthesizes Na/K Channels and Na-K ATPases

Stimulates existing Na and K channels to open as well

o Sodium moves from the pre-urine across the tubular epithelial cell

o Sodium is then pumped into the extracellular fluid into the blood

o Aldosterone has served to pull sodium back out of the urine and bring it back into the blood

Na re-absorption in the kidney

o Aldosterone does the opposite for potassium

Potassium is moved from the blood through the extracellular fluid into the urine

K secretion in urine

14 Major Endocrine Glands and Hormones

• Hypothalamus (Brain)

o Produces and secretes releasing and inhibiting hormones that regulate secretions by the anterior pituitary

Anterior pituitary secretes ACTH / TSH / FSH / LH

• These stimulate other glands as well as prolactin / GH / MSH / endorphins

o Produces ADH and oxytocin

Stored and released in the posterior pituitary

• Adrenal cortex

o Secretes cortisol and Aldosterone

• Adrenal medulla

o Secretes epinephrine and norepinephrine

• Pineal gland

o Secretes melatonin

Aids in sleep

• Thyroid gland

o Secrets thyroxine and triiodothryronine and calcitonin

Aids in metabolism

• Parathyroid glands

o Secrete parathyroid hormone

• Pancreas

o Islets of Langerhans secrete insulin and glucagon

o Blood glucose regulation

• Ovaries

o Secrete estrogens and progestins

• Testes

o Secrete androgens

15 The Hypothalamus and the Posterior Pituitary

• ADH and oxytocin are produced in the cell body of the hypothalamus and secrete through the nerve terminals of the posterior pituitary

o ADH antidiuretic hormone

“anti water flow”

• Oxytocin has effects on the uterus and mammary glands

o Stimulates contractions and milk production

• ADH causes kidney to reclaim water or produce less urine

o Prevents the kidney from producing large volume of urine

• Receptors for ADH are inhibited by alcohol

o Large dilute amounts of urine are produced

o Alcohol is a diuretic

16 The Hypothalamus and the Anterior Pituitary

• Hypothalamus produce and release RH (stimulating hormones) and IH (inhibiting hormones)

o Released through nerve terminals of hypothalamus

o Released into a capillary bed

o Move through a portal vein to a capillary bed in anterior pituitary

o In anterior pituitary, RH and IH trigger endocrine cells to release a number of substances

o Anterior pituitary hormones signals organs to release more hormones

• Hypothalamus is also the body’s center of temperature regulation

17 Anterior Pituitary Hormones

• Important AP (anterior pituitary) hormones:

o TSH thyroid-stimulating hormone

Stimulates thyroid gland

o ACTH adrenocorticotropic hormone

Stimulates adrenal cortex

o GH growth hormone

works with thyroid hormones to increase metabolism and promote growth

o FSH / LH gonadotropins

Affect reproductive organs

• Hormones released from one gland that acts on another gland are called tropic hormones

18 Anterior Pituitary Hormones

• Tropic effects only:

o FSH follicle-stimulating hormone / LH luteinizing hormone

Target: testes or ovaries

o TSH

Target: thyroid

o ACTH

Target: adrenal cortex

• Non-tropic effects (not required to know in detail)

o Prolactin

o MSH

• Non-tropic and tropic effects:

o GH

19 Hypothalamic-Pituitary-Thyroid Axis

• HPT axis is an example of thyroid and pituitary hormones working one after another to lead to an effect that releases hormones

• Hypothalamus releases thyroid-releasing hormones

o Moves through portal vein to anterior pituitary

o Causes AP to produce thyroid-stimulating hormones

o TSH moves through blood to thyroid gland to release thyroid hormones

o Thyroid hormones increase metabolism promoting growth

regulating development in maturation

Thyroid hormones:

• T4 – thyroxine

• T3 – triiodothryronine

o Thyroid hormones can release hormones that are independent of this axis

these independent hormones are involved in blood calcium regulation

20 Thyroid and Parathyroid Glands: Calcium Regulation

• Thyroid glands release calcitonin when calcium plasma levels are going up

o Decreases calcium level

• If calcium plasma levels go down, parathyroid hormones are released

o Increases calcium level

21 Calcium Homeostasis

• If plasma calcium goes up, thyroid glands release calcitonin to make it go down

• If calcium levels go down, parathyroid gland releases hormones (PTH) to make it go up

• Three target organs that affect calcium levels in the blood:

o Kidney

Increases or decreases its rate of secretion or uptake of calcium

• If calcium levels are high, kidney excretes calcium

• If too low, kidney increases its uptake of calcium

Involved in the activation of a form of vitamin D called calcitrol

• This substance helps to reabsorb calcium during low calcium levels

o Bone

Calcium levels low PTH triggers bone to give up its calcium to the blood

If levels are too high, calcitonin triggers the bond to take up calcium from the blood

o Intestine

Calcium levels low increase rate of absorption of calcium from ingested food

22 Hypothalamus-Pituitary-Adrenal Axis

• Inner cortex produces steroids

• Outer medulla produces catecholines

• Example of an initial stimulus low blood glucose

o Triggers hypothalamus to release corticol tropic releasing hormones

o Triggers anterior pituitary to release ACTH releasing hormones

o Triggers adrenal cortex to release cortisol

Cortisol causes blood glucose to increase (main idea to be grasped)

Cortisol has negative feedback

• Inhibits hypothalamus from release of corticol tropic releasing hormones

• Inhibits anterior pituitary from release of ACTH

23 The Adrenal Gland

• A general stress response

o Medulla is signalled to release more adrenaline by sympathetic nerve stimulation

o General fight or flight response involving adrenal glands

o We optimize cardiovascular respiratory function, increase blood pressure, increase breathing and metabolic rate and provide more fuel in the short term

24 Adrenergic Receptors (Adrenoceptors)

• Catecholines work by binding to particular receptor type called adrenal receptors

• Two main types of receptors:

o Alpha

o Beta

Can convert ATP AMP

• Both have different secondary messenger systems

• Leads to hormones having different responses on the same type of tissue depending on the present receptor

o Epinephrine acting on alpha receptor vessel constriction (intestinal)

o Epinephrine acting on beta receptor vessel dilation (skeletal)

25 The “Adrenal Gland” in Bony Fish

• Mammals have a medulla with distinct medulla and distinct cortex

• Fish don’t have adrenal glands

o The cells that produce catecholines and steroids are found lying in a

large vein the posterior cardinal vein (equivalent to the vena cava in humans) which flows into the heart

o There is sympathetic nerve stimulation

o The adrenal medulla is innervated by sympathetic nerves which stimulates the release of catecholines but there are other processes that produce this release as well (situational)

26 The Pancreas and the Islets of Langerhans

• Pancreas has both endocrine and exocrine function

o Exocrine function – pancreas secreting digestive enzymes into the intestines

o Endocrine function – pancreas takes up digestive enzymes from the intestines

• Throughout the pancreas, there are groupings of cells called islets of langerhans (containing beta and alpha cells)

• Beta cell – insulin (lowers blood glucose)

• Alpha cell – glucagon (raises blood glucose)

• Beta and alpha cells regulate blood glucose levels

27 Insulin

• As plasma glucose goes up, plasma insulin also goes up

o Insulin helps to move glucose into cells

-i.e. lower blood-glucose levels

o Insulin activates glucose transporters, allowing cells to take up glucose

o Food in gut triggers synthesis of insulin in anticipation of increasing blood-glucose levels

28 Blood Glucose Regulation

• Beta example:

o Initial stimulus: high blood glucose levels

o Beta cells in pancreas release insulin

o Insulin triggers cells in liver and other organs to take up glucose

o In the liver glucose becomes glycogen (for storage)

o Blood glucose levels decrease

• Alpha example:

o Initial stimulus: low blood glucose levels

o Alpha cells in pancreas release glucagon

o Glucagon signals liver to start breaking down glycogen to release glucose into the blood

o Blood glucose levels increase

29 Diabetes Mellitus

• Type I (insulin dependent)

o Failure of beta cells to release insulin into the blood

o Autoimmune disease

o Can be treated with insulin injections

o Very small fraction of total diabetes cases (~10%)

• Type II (non-insulin dependent)

o Resistant to insulin

o Beta cells can produce and release insulin into the blood but cells aren’t responding to insulin

o Insulin is unable to activate the messenger systems on the cell that allow for glucose intake

o Associated with long-term obesity

o Huge fraction of total diabetes cases (~90%)

30 Acute Complications of Diabetes Mellitus

• Diabetic Ketoacidosis

o Cells aren’t getting enough glucose because they are not taking up insulin

o Start to use fatty acids as energy source

o Liver converts fatty acids into ketones

o Ketones then circulate in the blood which produces symptoms similar to alcohol intoxication

• Dehydration

o Diabetes can cause dehydration

o High levels of glucose in the blood ends up being in urine (osmotic reactive molecule)

o If glucose is in the urine, you have to flush it out with more water

o The more glucose to get rid of the more water you have to get rid of

dehydration

31 Long-Term Complications of Diabetes Mellitus

• Atherosclerosis

o Build up fatty acid deposits in the inside of blood vessels

o Accumulation of fatty acid deposits leads vessel to become narrower and narrower

Narrow vessel inhibits blood flow

o Reduced or inhibited blood flow leads to heart tissue death heart attack / stroke

o Nitric oxide in healthy people keeps blood vessels dilated (less narrow)

o Diabetes don’t respond to nitric oxide so it doesn’t dilate their blood vessels when it becomes clogged

• Reduced peripheral circulation

o Reduced blood flow leads to damage in peripheral circulation

gangrene

32 Acute Complications of Diabetes Mellitus

• Blindness (Diabetic Retinopathy)

o Acute (short term) complication of diabetes

o Blood vessel damage in the eye reduced blood and oxygen supply

(ischemia) compensates by forming new blood vessels

(neovascularisation) new vessels are very weak (thin walls), break

easily and haemorrhage damaged eye tissue abnormalities in vision

33 The Pineal Gland

• Secretes melatonin (helps humans sleep)

• Release of melatonin triggered by darkness (produced more in the dark than in the light)

34 Atrial Natriuretic Peptide (ANP)

• Feedback system

o Secreted by cells in the atria (heart) in response to a stretch in the atrial wall (due to increase in plasma volume)

Blood volume increase blood pressure increase atrial stretch

atrial release of ANP ANP directly inhibits Na+ reabsorption and inhibits Aldosterone secretion which also inhibits Na+

reabsorption blood volume decreases blood pressure decreases