E n d o c r i n e S y s t e m

Section 1, Chapter 13

I n t r o d u c t i o n• The endocrine system assists the nervous system with communication and control of the body

• Characteristics of endocrine glands1. They are ductless2. Endocrine glands secrete hormones3. Hormones are carried to distant target cells through the

bloodstream4. Hormones only act on cells (target cells) that possess receptors

sensitive to the hormone – highly specific action.

1. Exocrine glands• Have ducts • Secrete chemicals directly onto a surface• Examples: sweat glands, mucous cells

2. Paracrine signals• Chemicals that affect only nearby cells• Example: prostaglandins secreted with semen stimulate

muscular contractions within female reproductive organs

3. Autocrine signals• Chemicals that affects only the cells that produced it.• Example: T-cells secrete interleukins (IL), which stimulate the

proliferation of the T-cells (monoclonal population)

4. Neuroendocrine • Nervous tissue that secretes hormones• Example: hormone secretion from the hypothalamus.

O t h e r s i g n a l s

Endocrine vs. Nervous TissueThe endocrine and nervous systems communicate using chemical signals• Neurons release neurotransmitters into a synapse affecting

postsynaptic cells

• Endocrine glands release hormones into the bloodstream to specific target cell receptors

Figure 13.2 Chemical communication. (a) neurons release neurotransmitters onto synapses, affecting postsynaptic cells. (b) Glands release hormones into the bloodstream. Blood carries hormone molecules throughout the body, but only target cells respond.

Endocrine vs. Nervous Tissue

Cell…………………………………. Neuron Glandular EpitheliumSignal………………………………. neurotransmitter hormoneSpecificity of action…………. receptors on postsynaptic cell receptors on target tissuesSpeed of onset……………...... <second seconds to hoursDuration of action……………. usually very brief may be brief or last for days

Nervous System Endocrine System

Chemistry of Hormones

• Chemically, hormones are either:1. Steroid or steroid-like hormones

2. Biogenic Amines

3. Peptide hormones

Steroid Hormones

Include• Estrogen• Testosterone• Androgens (weak sex hormones)• Aldosterone• Corticoids (hormones secreted from the adrenal cortex)

Properties• Steroid hormones are derived from cholesterol• They are composed of hydrophobic lipids (insoluble in water)

Biogenic AminesProperties• Amines are synthesized from amino acids

Include• Norepinephrine• Epinephrine• Melatonin • Thyroid hormones (these are also hydrophobic, or water insoluble)

Peptide HormonesProperties• Composed of long chains of amino acids (polypeptides)

Include• Hypothalamic hormones• Pituitary hormones• Pancreatic hormones• Gastrointestinal hormones

Water Solubility & Membrane PermeabilitySteroid + Thyroid Hormones• Are hydrophobic – transported in the plasma attached to proteins

• Cell membrane permeable – due to their hydrophobic properties, these hormones readily cross the phospholipid bilayer of the cell membrane.

All other Hormones• Are hydrophilic– freely dissolved in plasma

• Cell membrane impermeable – these hormones do not cross the cell membrane, and must rely on 2nd messengers to relay a signal into target cells.

• 2nd messenger – molecule that relays and amplifies a hormone signal into the cell.

Actions of steroid hormones

1. A steroid hormone crosses the cell membrane2. Hormone combines with a protein receptor in the nucleus3. The hormone-receptor complex activates transcription of a specific DNA region4. The mRNA leave the nucleus into the cytoplasm 5. The mRNA is translated into a protein.

Actions of Non-steroid

hormones

1. A non-steroid hormone reaches the target cell,2. The hormone binds to a membrane receptor3. Binding to the receptor activates an enzyme in the cell membrane (adenlyate cyclase)4. Adenlyate cyclase converts ATP into cyclic adinosine monophosphate (cAMP)5. cAMP is a second messenger that promotes a series of reactions leading to the cellular

changes associated with the hormone’s action.

Control of Hormonal SecretionsHormone secretion is generally controlled in three ways:1. Negative Feedback2. Hormone Deactivation3. Up/Down Regulation

Negative Feedback

Figure 13.10 Hormone secretion is under negative feedback.

The endocrine gland, or system controlling it senses the concentration of the hormone that gland secretes.

When the level of a specific hormone drops below needed levels, the endocrine gland is stimulated to secrete more hormone.

As the hormone concentration reaches the needed level, stimulation of that endocrine gland is reduced, and production of that hormone is reduced.

Figure 13.8 Examples of endocrine system control. (a) one way the hypothalamus controls the anterior pituitary, which in turn controls other glands (b) the nervous system controls some glands directly, and (c) some glands respond directly to changes in the internal environment.

Indicates negative feedback inhibition.

Negative Feedback

Figure 13.11 As a result of negative feedback, hormone concentration s remain relatively stable, although they may fluctuate slightly above and below average concentrations.

Hormone DeactivationHalf-life: measures the time for half of the hormone molecules to be removed from plasma

Example of half-life: a hormone with a half-life of 10 minutes, decreases in concentration by half every 10 minutes.

Time Hormone Concentration 0 minutes 100%10 minutes 50%20 minutes 25%30 minutes 12.5%

Hormones are continually secreted in the urine, and broken down by enzymes, primarily in the liver.

Up/Down RegulationUp-regulation increases the number of receptors on the target cell• Up regulation increases a cell’s sensitivity to a hormone

Down-regulation decreases the number of receptors on target cells.• Down regulation decreases a cell’s sensitivity to a hormone

E n d o c r i n e S y s t e m

Section 2, Chapter 13

Pituitary Gland (Hypophysis)Location: Lies at the base of the brain in the sella turcica, connected to hypothalamus by a pituitary stalk (infundibulum)

2 Lobes:Anterior pituitary (adenohypophysis) Posterior pituitary(neurohypophysis)

Control of Pituitary Gland

Releasing hormones secreted from hypothalamus regulates the anterior lobe.

Nerve impulses from hypothalamus regulate the posterior lobe.

Anterior Pituitary Gland Posterior Pituitary Gland

Anterior Pituitary GlandHypophyseal Portal System –• Releasing hormones secreted by the hypothalamus are conveyed to

the anterior gland through Hypophyseal portal veins.

• Releasing hormones act on specific target cells within the anterior pituitary gland

• In response, the pituitary gland secretes tropic hormones that travel throughout the body acting on distant target cells.

Tropic hormone = hormones that have other endocrine glands as their target

Example of hypophyseal pathway

Releasing Hormone:Thyroid releasing Hormone (TRH) secreted from hypothalamus

Tropic Hormone:Thyroid Stimulating Hormone (TSH) is secreted from the anterior pituitary

Target Cells:Thyroid Hormone (Thyroxine) is secreted from thyroid glands

Anterior Pituitary Hormones 1. Growth Hormone (somatotropin)

Target Cells: • Epithelial and Connective Tissue• Adipose Tissue• Liver

Actions of GH: • Promotes cell growth and division, especially in

skeletal muscles and chondrocytes• Promotes breakdown and use of fat for energy• Liver: promotes breakdown of glycogen for energy

Hypothalamic Control of GH:• Growth Hormone Releasing Hormone (GHRH):

promotes GH secretions• Somatostatin: inhibits GH secretion

Growth Hormone Disorders

Hypopituitary Dwarfism• Insufficient GH during development• GH therapy may treat condition if

administered before the epiphyseal plates ossify

Gigantism• Results from oversecretion of GH in childhood• Usually caused by a tumor of the pituitary gland

Anterior Pituitary Hormones 2. Thyroid Stimulating Hormone (thyrotropin)

Hypothalamic Control of TSH: Thyroid Releasing Hormone

Target Cells: Thyroid Gland

Actions: TSH promotes secretions of thyroid hormones(T3 & T4)

Under normal conditions, T3 and T4 inhibit further secretions of TRH and TSH

Thyroid Hormones and Negative Feedback

Iodine obtained from the diet is essential for thyroid hormone (T3 & T4) synthesis

TRH & TSH continually stimulate the thyroid gland without inhibition.

Goiter = enlarged thyroid gland

An Iodine deficiency prevents the formation of Thyroid Hormones.

Anterior Pituitary Hormones 3. Prolactin (mammotropin)

Hypothalamic Control of PRL: • Prolactin Releasing Factor: promotes secretion of prolactin• Prolacting Release Inhibiting Hormone: inhibits PRL secretion

Target Cells: Mammary Glands

Actions: Prolactin promotes milk production

3. Adrenocorticotropic Hormone (ACTH)

Anterior Pituitary Hormones

Hypothalamic Control of ACTH: Corticotropin Releasing Hormone

Target Cells: Adrenal Cortex

Actions: ACTH promotes secretions of hormones from the adrenal cortex (e.g. cortisol)

Anterior Pituitary Hormones 4. Follicle Stimulating Hormone (FSH) 5. Luteinizing Hormone (LH)

Hypothalamic Control: Gonadotropin Releasing Hormone (GRH)

Target Cells: GonadsMale: testes Female: Ovaries

4 & 5 = gonadotropes

Actions of gonadotropes: Follicle Stimulating Hormone:

Female = promotes development of ovarian folliclesMale = promotes development of sperm

Luteinizing Hormone:Female = promotes the secretion of estrogens and progesteroneMale = promotes the production of testosterone

Figure 13.15 Hormones released from the hypothalamus, the corresponding hormones released from the anterior lobe of the pituitary gland, and their target organs.

Posterior Pituitary GlandStructurally consists of neurosecretory cells

Hormones are produced by the hypothalamus, then released from the posterior pituitary gland.

Posterior Pituitary Hormones1. Antidiuretic Hormone (ADH) (also called vasopressin)

Target Cells: Kidneys & Blood Vessels

Actions of ADH depend the receptors to which it bindsV1 receptors• Located within blood vessels• ADH, in high concentrations promotes vasoconstriction• May prevent a drop in blood pressure with profuse bleeding

V2 receptors• Located within tubules of kidneys• ADH promotes water reabsorption at the kidneys, and thus

decreases water loss.

• Alcohol inhibits ADH secretion, which explains its role as a diuretic.

Posterior Pituitary Hormones2. Oxytocin

Actions of OxytocinFemales: • stimulates smooth muscle contractions in the uterus during delivery• Promotes ejection of milk from mammary glands

Males: Function is unknown

End of Section 2, Chapter 13.

E n d o c r i n e S y s t e m

Section 3, Chapter 13The Peripheral Endocrine Glands

Thyroid GlandLocation: The thyroid gland is located just inferior to the larynx.

Structure: • It consists of two lateral lobes connected by an isthmus• Contains several follicles.

Thyroid Gland FolliclesFollicles consists of simple cuboidal epithelium & a colloid center

Follicular Cells: produce T3 & T4

Coloid: contains Thyroglobulin, which is a storage form of thyroid hormones.

Follicular Cells take up thyroglobulin by endocytosis, then release the thyroid hormones into the bloodstream.

Extrafollicular Cells: produce Calcitonin

Thyroid HormonesTarget Cells: T3 & T4 affect many cells throughout the body.

Actions of T3 & T4: Raise Metabolic Rate• Increase rate of carbohydrate catabolism• Enhance protein synthesis• Promotes the breakdown and use of lipids

T3 & T4 are major factors in determining the basal metabolic rate (BMR) BMR = calories required to sustain life

Thyroid HormonesFollicular cells require iodine salts (iodide) to produce T3 and T4.

• Nearly 75% of thyroid hormones are attached to thyroid binding globulins. • Only the small amounts of the unbound hormones act on target cells.

T3 & T4 are hydrophobic molecules (insoluble in water)

T4 accounts for 95% of circulating Thyroid Hormone, But…

Transport of Thyroid Hormones

T3 is physiologically more active. • T3 is 5 times as potent as T4 • T3 also has a 50-fold higher “free” concentration in the plasma (see figure below).

Thyroid DisordersHypothyroidism – insufficient T3 & T4• During infancy – results in intellectual disability, stunted

growth, abnormal bone formation (cretinism)

• During adulthood – low metabolic weight, sluggishness, poor appetite, and sensitivity to cold

Hyperthyroidism – excess T3 & T4• Results in high metabolic rate, hyperactivity, weight loss,

sensitivity to heat, and exophthamia (protruding eyes)

• Grave’s Disease • Autoimmune Disorder: Antibodies target the thyroid

gland and mimic TSH. Thyroid antibodies overstimulate thyroid gland, resulting in hyperthyroidism.

Grave’s disease may cause exophthalmia

Infantile hypothyroidism

CalcitoninExtrafollicular cells (C-cells) secrete Calcitonin

Calcitonin lowers blood calcium concentrations.

• Stimulates Osteoblast activity – increases bone deposition

Major Source of Control: elevated blood calcium ion concentration

Actions of Calcitonin

• Inhibits osteoclast activity – reduces bone resorption• Promotes the excreting of calcium from the kidneys

Parathyroid Glands• Location:

4 small parathyroid glands are located on the posterior aspect of the thyroid gland

•Hormone: PTH (parathyroid hormone)

One parathyroid gland surrounded by thyroid follicles.

Parathyroid Hormone elevates blood calcium levels.

Parathyroid Hormone (PTH)

• Stimulates Osteoclast activity – increases bone resorption

• PTH also promotes the activation of Vitamin D, which enhances calcium absorption from the small intestine.

• Inhibits osteoblast activity – reduces bone deposition

• Promotes calcium reabsorption from the kidneys.

Actions of PTH:

Major Source of Control: Inadequate blood calcium ion concentration

Figure 13.27 Parathyroid Hormone (PTH) stimulates bone to release Calcium (Ca2+) and the kidneys to conserve calcium. It indirectly stimulates the intestine to absorb calcium. The resulting increase in blood calcium concentration inhibits secretion of PTH by negative feedback.

Calcitonin and PTH have opposing effects on the levels of calcium ions in circulation. Both work together to maintain calcium homeostasis.

Adrenal GlandsLocation: The adrenal glands are located on the superior aspect of the kidneys.

Structure: • Adrenal glands are pyramid shaped organs that consist of two parts

• Adrenal Medulla = secretions controlled by sympathetic nerve fibersAdrenal Cortex = Under hormonal control

Hormones of the Adrenal Medulla

Hormones: Norepinephrine (noradrenalin) & Epinephrine (adrenalin)• Both are classified as catecholamines.

Nerve fibers control secretions: Hormones of the adrenal medulla are under control by the sympathetic division (fight or flight) of the ANS.

Actions: Effects are similar to sympathetic nerve fibers, but longer lasting. • Increases heart rate and force of contraction• Increases blood pressure• Increases metabolic rate• Increases blood glucose levels (primarily epinephrine)• Decreases digestion

Beta Blockers• Epinephrine & Norepinephrine exert their effects by binding to Beta (ß)

adrenergic receptors in heart and walls of the blood vessels.

• Beta blockers bind to ß-receptors, thus obstructing the binding of catecholamines.• Hence beta blockers reduce sympathetic influences of the heart and blood vessels.• Therefore, beta blockers decrease heart rate, contractility, and reduce blood pressure.

Hormones of the Adrenal Cortex

3 Layers of the adrenal cortex secrete over 30 types of steroid hormones.

Hormones

Aldosterone – produced in zona glomerulosa

Cortisol – produced in zona fasciculata

Androgens – produced in zona reticularis

Hormones of the Adrenal Cortex1. Aldosterone (mineralocorticoid)

• regulates Na+ and K+ concentrations• regulates blood pressure

Actions• Aldosterone causes the kidneys to reabsorb Na+ and to excrete K+

• Aldosterone indirectly raises blood pressure: Increased Na+ reabsorption increases water reabsorption by osmosis.

Controls of Aldosterone Secretion• Low blood pressure stimulates aldosterone secretion (renin-angiotensin-aldosterone pathway)• Elevated blood K+ concentration promotes aldosterone secretion

• Low Na+ has only a slight effect on aldosterone secretion.

Renin-Angiontensin-Aldosterone System

ACE Inhibitors block the actions of ACE, and thus lower blood pressure.

Hormones of the Adrenal Cortex2. Cortisol (glucocorticoid)

• Its primary effect is to build up and conserve blood glucose supplies• Its actions keep blood glucose levels constant between meals.

Actions

• Inhibits protein synthesis: amino acids used in gluconeogenesis

• Promotes gluconeogenesis in the liver gluconeogenesis = glucose synthesis from non-carbohydrates

• Promotes the release and used of fatty acids from adipose for energy. Using fatty acids for energy allows glucose to be conserved.

Hormones of the Adrenal Cortex3. Androgens• Supplement the sex hormones secreted from the gonads.• Androgens may be converted into testosterone and estrogens.

The PancreasStructure & Location: The pancreas is located posterior to the stomach,

attached to the duodenum.

The pancreas has both digestive and endocrine functions.• Pancreatic Islets (Islets of Langerhans) = endocrine cells

• Digestion cells (we’ll discuss these with the digestive system)

Cells of the Pancreatic Islets3 distinct type of cells secrete 3 hormones:

• Alpha Cells – secrete glucagon• Beta Cells – secrete insulin• Delta Cells – secrete somatostatin

Pancreatic hormones regulate the storage, use, and release of fuels (glucose).

Pancreatic Hormones

1. Glucagon

Overall Effect: During fasting, when blood glucose levels drop, glucagon elevates blood glucose levels

Actions of Glucagon:• Stimulates glycogenolysis in the liver (breakdown of glycogen into glucose)

• Glucagon also promotes gluconeogenesis

• Glucagon also stimulates the breakdown of fats into glycerol and fatty acids.• Glycerol is used in gluconeogenesis• Fatty Acids are metabolized for energy

glycogen

Gluconeogenesis

Amino acids glycerol

glucose

Glycogenolysis

glucose

Liver

Glucagon secretions elevates blood glucose concentrations.• Gluconeogenesis converts noncarbohydrates, such as amino acids and

glycerol, into glucose.

• Glycogenolysis breaks down large glycogen molecules into glucose.

2. Insulin

Pancreatic Hormones

Overall Effect: Following a meal, when blood carbohydrate levels are high, insulin removes excess glucose from the blood.

Actions of Insulin:• Stimulates glycogenesis in the liver (formation of glycogen from glucose). • It inhibits gluconeogenesis.• Insulin promotes glucose uptake in adipose tissue, skeletal muscles, and cardiac

muscle.

3. Somatostatin

Overall Effect: Helps regulate glucose metabolism by inhibiting the secretion of glucagon and insulin.

Hormonal Control of Glucose

Insulin and glucagon function together to stabilize blood glucose concentration. Negative feedback responding to blood glucose concentration controls the levels of both hormones.

Diabetes Mellitus

Type I Diabetes Mellitus (juvenile)• Autoimmune disease – immune system destroys beta cells, resulting in the loss of

insulin production.

• Without insulin, blood glucose cannot be taken up and used for energy.

• Glucose accumulates in the blood and urine = hyperglycemia.

Type II Diabetes Mellitus (adult onset)• Receptors on target cells wear down and become insensitive to insulin.

• Target cells resist glucose uptake, even in the presence of insulin.

• Insulin levels must be higher than normal just to maintain normal glucose concentrations.

Other Endocrine GlandsPineal Gland

• The pineal gland secretes melatonin, which regulates circadian rhythms (sleep/wake cycle)

• Located posterior to thalamus.

• Melatonin secretions are greatest in dark. Light inhibits secretions.

Thymus Gland• Secretes thymosins• Promotes development of certain lymphocytes• Important in role of immunity

Reproductive Organs• Ovaries produce estrogens and progesterone• Testes produce testosterone• Placenta produces estrogens, progesterone, and gonadotropin

Other organs: digestive glands, heart, and kidney

Other Endocrine Glands

End of Section 3, Chapter 13