A+P 2: Endocrine system

The endocrine system

Coordinates whole body responses to stimuli through use of hormones, and is how the body knows when to eat, sleep, grow. Consists of cells and glands that secrete hormones

Manages intercellular communication via chemical messengers, signals travel short or long distances to target cells, speed is slower than NS

Slower acting and maintains internal environment, broad-scale effects

Exocrines

Substances that are secreted into ducts that lead outside of the body (ex. sweat - sweat glands, breast milk - mammary glands, digestive enzymes - pancreatic ducts, digestive/gut tube)

Endocrines

Extracellular signaling molecules secreted by cells. Bind to receptors on or in target cells and affect their cellular function (organs, hormones, receptors that release the hormones)

Hormones

Endocrines that travel in the blood or lymph to reach distant cells. Will only affect if target call has a receptor for the hormone (no receptor, no response)

Hormone receptor

Recognizes a specific molecule based on shape/side groups

Glands

Clustered cells that secrete hormones

Major glands in the ES

Hypothalamus, pituitary, pineal, thyroid, thymus, ovary, testicles, pancreas, adrenals, placenta

Other important cells in the ES

Cells in the kidneys, adipose/fat cells, heart cells, bone tissue

Autocrine glands

Affects itself when releasing hormone

Paracrine glands

Affects nearby cells/things

10 key concepts for understanding hormones

1. Receptors are needed for a hormone to affect a cell

2. The # of receptors on a particular target cell can vary over time

3. Hormones can interact to affect the response of target cells

4. Hormones are secreted in small amounts and are effective at very low concentrations

5. Breadth of hormone impact can vary greatly

6. A hormone can have many different effects; depends on nature of the target cells

7. Sometimes, chemicals that serve as hormones also have non hormonal functions

8. Gland can secrete more than one type of hormone

9. Same hormone be secreted by different cell types/glands

10. a change in stimulus will affect hormone secretion

1. Receptors are needed for a hormone to affect a cell

Hormone receptors can be on the cell membrane or inside the cell (cytoplasm or nucleus)

2. The # of receptors on a particular target cell can vary over time

Upregulation = increasing

Downregulation = decreasing

Thyroid hormone upregulates the number of receptors for epinephrine

3. Hormones can interact to affect the response of target cells

Permissive effect

Synergistic effect

Antagonist effect

Permissive effect

One hormone enables another to have an effect

Synergistic effect

Two hormones w/ similar effects generate an out of proportionate response (small amount + small amount = really big amount)

Antagonist effect

Two hormones have opposing actions (both bind, nothing happens)

4. Hormones are secreted in small amounts and are effective at very low concentrations

Example: Thyroid gland produces about 90-100 micrograms of hormone daily ( a little more than one grain of salt)

5. Breadth of hormone impact can vary greatly

Narrow target and effect: Ex. Oxytocin mainly targets tissues in breasts and uterus contraction

Broad target and effect: Ex. Epinephrine targets many tissues (fight or flight)

6. A hormone can have many different effects; depends on nature of the target cell

Blood vessels with beta receptors dilate, alpha receptors constrict

Ex. Epinephrine = “fight or flight”: increased heart rate, release stored energy from liver and fat cells, sends blood to skeletal muscles (constriction leading to gut and skin, dilation leading to muscles)

7. Sometimes, chemicals that serve as hormones also have non-hormonal function

Ex. Norepinephrine is a hormone and neurotransmitter

8. Glands can secrete more than 1 type of hormone

Different hormones are typically (but not always) secreted from different cell types

Ex: Pancreas secretes insulin, glucagon, etc. Also an exocrine gland & secretes digestive enzymes

9. Same hormone can be secreted by different cell types/glands

Ex. Testosterone is produced by testes and adrenal glands

10. A change in stimulus will affect hormone secretion

Hormone levels in blood are usually kept within narrow range (response by target cell affects the stimulus). Stress response increases levels dramatically, but most hormones shouldn’t vary too greatly

*Can affect behavior

Homeostasis

Body systems working together to maintain a stable internal environment. systems respond to external and internal changes to function within a normal range (body temp, fluid balance, etc.) Systems have a set-point and normal range of function (ex. internal body temp)

• Set points can change! Ex. Fever helps body fight pathogens by making it too hot

• Also: water, ions, blood pressure, light input, blood glucose, hormones, gasses

Receptor

Receives stimulus

Control center

Processes signal and produces an effector

Effector

Either reinforces (increases) or inhibits (decreases) stimulus

Negative feedback loops

Opposes variations from normal (go towards normal). Response by target cells inhibit (lower) hormone secretion. Responses to hormone secretion lower stimulus, normal range is achieved (homeostasis maintained)

Positive feedback loops

Exaggerates variations from normal (away from normal). Response by target cell increase hormone secretion. Less common, usually bad. Response to hormone is increased = normal range is LOST! Some temporary loops are important (release of oxytocin during birth and blood clotting)

3 main classes of hormones

1. Protein/peptide hormones

2. Steroid hormones

3. Amine hormones

Protein/peptide hormones

Chains of linked of amino acids (peptide < protein)

Most common: oxytocin and insulin

Binds to receptors on target cell membrane

Water soluble

Moves in blood freely and easily

Primary effect: quick, triggers cascade. 1st: hormone (activates 2nd) 2nd: activates protein kinases (enzymes)

Steroid hormones

Synthesized from lipid cholesterol

Ex. Testosterone and estradiol.

Hormone can pass through target cell membrane (lipid soluble) and binds to receptors IN the cell

Works with carrier protein to move in blood

Slower, longer lasting

Amine hormones

Synthesized from amino acid tyrosine or tryptophan

Some water-soluble, some lipid-soluble

Ex. thyroid hormone (lipid soluble), epinephrine and norepinephrine (water soluble)

Hypothalamus and pituitary

Main connection between brain and endocrine system

Hypothalamus

“Control center” region of the brain that integrates info and innervates the pituitary

Pituitary

“Master gland”, underneath hypothalamus (rests in sella turcica). Composed of anterior and posterior

Pituitary stalk

AKA infundibulum. Connects hypothalamus and pituitary. Contains blood vessels and axons

Posterior pituitary

Portion of brain that grows down during embryonic development. Has neurosecretory cells that extend down from the hypothalamus.

Secretes two hormones: Oxytocin and antidiuretic hormone (ADH)

Oxytocin

Released from ant. pituitary straight to target glands

Main target: uterine muscles and mammary glands

Stimulates uterine contractions during child birth

Stimulates the release of milk

Also targets “love hormone” regions of the brain

Antidiuretic hormone (ADH)

Main target: kidneys

Tells kidneys to reabsorb water, less water is urinated

Maintains body water homeostasis, AKA vasopressin

Anterior pituitary

Portion of developing mouth that grows up and breaks free (not physically attached to hypothalamus).

Secretes 6 hormones stimulated by releasing hormones (RHs) from the hypothalamus:

1. Prolactin

2. Growth hormone

3. Gonadotropins (luteinizing hormone and follicle stimulating hormone)

4. Thyroid stimulating hormones

5. Adrenocorticotropic hormones

Prolactin

Main target: mammary glands

Stimulates mammary to produce milk

Growth hormone

• Main target: many cells and stimulates anabolic (‘building’) processes

• Provides energy via: fat (adipose) and liver (release of stored glucose

• Growth effects: increases uptake of amino acids into cells, promotes cell proliferation (bone cells, muscle cells, nervous cells)

• IGF-1: stimulates liver to produce IGF-1 which causes growth

• Too much: Giantism

• Too little: Pituitary dwarfism

Gonadotropins

• Tropic hormone

• Ant pituitary → gonadotropins (LH, FSH) → gonads → testosterone, estrogen, progesterone

• LH and FSH

Luteinizing hormone and follicle stimulating hormone

Regulate growth and actions of the gonads (including hormone production). Stimulates gonads to produce sex hormones: testosterone (testes), estrogen & progesterone (ovaries)

Testosterone (testes), estrogen & progesterone (ovaries)

Regulate reproductive function and development of secondary sexual characteristics (breasts, facial and pubic hair, etc.)

Hypothalamus pituitary gonadal (HPG) axis

Regulates release of sex hormones. At puberty, hypothalamus becomes less sensitive to negative feedback from the sex hormones (producing more)

Thyroid stimulating hormone (TSH)

• Tropic hormone

• Stimulates thyroid gland to produce thyroid hormones (T3 and T4)

Ant pituitary → TSH → thyroid → thyroid hormones (T3 and T4)

Thyroid hormones (T3 and T4)

Regulate metabolic rate of cells (more hormone, higher levels of metabolism)

• Lipid soluble amine hormones, bind to receptors in target cells and stimulate production of gene products that increase cellular metabolism

• Heat is a metabolic byproduct

• T3 and T4 differ in number of iodine molecules (only body process that uses iodine)

• T4 is produced in higher concentration but T3 is the more metabolically active form. Target cells contain deiodinase enzymes (converts T4 to T3 by removing an iodine)

Thyroid gland

Secretes multiple hormones:

• Thyroid hormones (T3 and T4) (produced by thyroid follicles)

• Calcitonin (produced by parafollicular cells)

Follicle cells - line outside of follicle, secretes thyroglobulin and iodine into colloid

Colloid - substance inside follicle, enzymes link iodine to thyroglobulin

Hypothalamus pituitary thyroid (HPT) axis

Regulates release of thyroid hormones

1. Hypothalamus secretes thyrotropin releasing (TRH)

2. TRH stimulates anterior pituitary to release TSH

3. TSH causes thyroid to release T3 and T4 (negative feedback from T3 and T4 keeps thyroid hormones in a constant range)

Hyperthyroidism

Too much thyroid hormone. Weight loss, increased appetite, anxiety, increased growth, fast heart rate

Goiter

Enlarged thyroid gland, most common cause is not consuming enough iodine

Hypothyroidism

Too little thyroid hormone. Weight gain, decreased appetite, slow heart rate, fatigue

Adrenocorticotropic hormone (ACTH)

• Tropic hormone

• Stimulates cortex of adrenal gland to produce glucocorticoids (cortisol)

• Act to ensure you have energy available during times of stress (some synthetic ones are used to stop inflammatory responses)

  • Promotes breakdown/release of stored energy (carbs/fats)

  • Suppresses some systems so more energy can go immediately to important systems (muscles, heart)

  • Can make you hungry

• Ant pituitary → adrenocorticotropic hormone (ACTH) → adrenal cortex → cortisol

Cortisol

Stress hormone (increases when you wake up, slowly decreases during the day). Released by adrenal cortex

• Ant pituitary → adrenocorticotropic hormone (ACTH) → adrenal cortex → cortisol

• Moves slower, steroid

Hypothalamus pituitary adrenal (HPA) axis

Regulates the release of cortisol (negative feedback keeps cortisol from getting too high)

1. Hypothalamus secretes corticotropin releasing hormone (CRH)

2. CRH stimulates anterior pituitary to release adrenocorticotropic hormone (ACTH)

3. ACTH causes adrenal gland (cortex) to release cortisol

Adrenal cortex

Top: Mineralcorticoids, Ex. Aldosterone

Middle: Glucocorticoids, Ex. Cortisol

Bottom: Androgens

Adrenal Medulla

Produces Epinephrine and norepinephrine

Stress situations trigger quick and slower, longer-lasting responses

Quick, almost immediate: Epinephrine, norepinephrine (regulated by sympathetic NS)

Slower: Glucocorticoids; e.g. cortisol (regulated by hypothalamus/anterior pituitary) (lipid soluble) (longer lasting)

Epinephrine/norepinephrine

Released from cells of adrenal medulla, provides quick, short-term response to stressful situations

• Increased heart rate and contractile force

• Release stored energy from liver and fat cells

• Sends blood to skeletal muscles (constriction of vessels → gut and skin) (dilation of vessels → muscles)

Aldosterone

• Produced by adrenal cortex

• Mineralocorticoid that regulates the body’s mineral content (K+ and Na+) ← electrolytes/ions

• Important for electrolyte and water balance in the body (and therefore blood pressure)

Neurosecretory cells

Cells of nervous system that secrete hormones of neurohormones. Ones in hypothalamus extend into posterior pituitary

Hormone secretion - posterior pituitary

1. Hormones are synthesized in the part of the cell within the hypothalamus and then travel down the cell into posterior pituitary

2. When secreted, hormones diffuse into the capillary bed within the posterior pituitary and then travel throughout the body in the blood

Hormone secretion - anterior pituitary

1. Neurosecretory cells in hypothalamus secrete “releasing” hormones (RHs) into a capillary bed

2. RHs travel via a portal blood vessel to another capillary bed located in anterior pituitary

3. RHs diffuse into cells of anterior pituitary gland and stimulate those cells to produce hormones

4. Hormones produced by cells of the anterior pituitary gland diffuse into the anterior pituitary gland capillary bed and travel throughout the body in the blood

*RIHs are also produced

Hypothalamus → ant. pituitary → tropic hormone → endocrine gland → hormone

Release inhibiting hormones (RIHs)

Stop production of hormones by anterior pituitary cells

Hypophyseal portal system

‘Capillary portal vessel capillary’ arrangement between hypothalamus and pituitary.

Capillary beds usually drain into venous blood (artery → capillary → vein

Occasionally, a capillary bed will lead to a portal blood vessel that branched into another capillary (known as a portal system) (uncommon, double capillary)

Hormonal cascade

Some anterior pituitary hormones cause other endocrine glands to secrete hormones

Tropic hormones

Stimulate other cells to release a hormone (which then affects the tissues, etc.). Secretes by anterior pituitary after stimulated by RHs

Androgens

• Produced by adrenal cortex

• Include testosterone and similar hormones (“male” hormones, but also also produced by females in lower levels)

• Affects reproductive anatomy and development

• Can be converted into estrogens

Calcitonin

Secreted by thyroid gland, produced by parafollicular cells. Secreted when blood calcium is high. Lowers blood calcium by stimulating bone deposition and growth → more calcium is stored in the skeleton

Parathyroid hormone (PTH)

Produced by the parathyroid glands (4 small glands located posterior to the thyroid gland). Secreted when blood Ca²⁺ is low. Raises blood calcium by stimulating:

• Bone breakdown (release of calcium into the blood)

• Retention of calcium by kidneys (less lost in urine)

• Bioactivation of vitamin D (more absorption of calcium from food in the intestines)

Parathyroid → parathyroid hormone

Main regulator of blood Ca²⁺

Blood calcium homeostasis

High

1. If calcium levels in the blood rise above a set point

2. Thyroid gland releases calcitonin

3. Blood calcium levels fall

Low

1. If calcium levels fall below a set point

2. Parathyroid glands in the thyroid release parathyroid hormone

3. Blood calcium levels rise

Pancreas has ______ and _____ functions

Exocrine and endocrine

Glucagon

Produced by alpha pancreatic islet cells, secreted when blood glucose is low

Increases blood glucose by stimulating breakdown of glycogen and creation of glucose from other non-carbohydrate substrates in the liver (glucogenesis from amino acids and glycerol from fats)

Pancreas → glucagon

Insulin

Produced by beta cells. Secreted when blood glucose is high. Decreases blood glucose by allowing it to enter fat and muscle cells (also stimulates fat and protein synthesis)

Causes glucose transporters to temporarily relocate to plasma membrane (so glucose can enter cell)

Without insulin, glucose can’t enter any cells → body will switch to relying on fat metabolism (ketosis)

Pancreas → insulin

Gluconeogenesis

Formation of glucose from fat and protein substrates

When stored glucose is low:

Body increases use of fat for energy (ketosis)

Ketones are created during fat metabolism (important because the brain can only use glucose and ketones for energy)

Ketones that are not used to form ATP are broken down into acetone anf CO₂ and exhaled from the body

Blood glucose homeostasis

Maintained by the antagonistic actions of:

• Insulin (removes glucose from blood)

• Glucagon (release glucose into blood)

Diabetes mellitus

“Sweet urine”

A group of diseases characterized by an inability to produce or use insulin → high blood sugar (hypergylcemia)

Most common are types 1 and 2

Type 1 diabetes

Autoimmune attack on beta cells → little/no insulin produced (bad smelling breath - high ketone production, impaired growth increased thirst, peeing more)

Type 2 diabetes

Cells don’t respond appropriately to insulin

“insulin resistance”

No response, insulin is being produced but not generating any responses

Insulin is still working to a certain degree, but very much less of an effect