Physiology - Exam 2

Endocrine System, Musculoskeletal System

“Classic” Endocrine Glands

Whole organs

Examples: Pituitary, pineal, thyroid, adrenal

“Diffuse” endocrine glands

Scattered cells within other organs

Ex: Hypothalamus, skin, heart, liver

Endocrine glands release

Hormones

Hormones are

Chemical Messengers

Endocrine gland secretion vs. exocrine gland secretion

Endocrine glands are ductless (no duct involved)

Exocrine glands secrete using a duct

Endocrine cells can secrete compunds into (2)

1. Directly to the ECF (extracellular fluid - bloodstream)

2. Directly to the external environment (Not common in humans — pheromones)

Hormone function (general/broad scheme)

Regulation of long-term ongoing functions in the body

Hormone functions (more specific - 4)

1. Metabolism

2. Development

3. Growth

4. Reproduction

Hormone defects are ______

Catastrophic (Because hormones are involved in major long-term functions)

Endocrinology

The study of hormones (involves use of synthetic hormones and medical procedures in medical field)

Hormone Signaling pathway

Producing cel → ECF → Blood Vessel → circulates in bloodstream → diffuses to target

4 Key prinicples of Hormone Signaling

1. Small Quantities (hormones exist in picomolar or nanomolar conc. = hard to study)

2. Limited Duration (fixed, short half-lives)

3. Distant, specific targets (long-range, but specific)

4. Bind unique receptors (Allows for specificity)

Hormones can control (3)

1. Rates of enzymatic reactions

2. Transportation of materials across membranes

3. Gene expression and protein synthesis

What factors can influence a hormone’s effect

1. Duration - the time the hormone is available

2. The effects of other hormones

How does Duration influence a hormone’s effect

Hormones have limited signaling time (to be able to respond to dynamic changes)

• Degraded by enzymes in the liver and kidneys with the by-products excreted (in bile or urine) or recycled

The influences of other hormones on hormone action (4)

1. Additive

2. Synergistic

3. Permissive

4. Antagonistic

Additive influences on hormone effect

If both hormones are present, there’s the same net effect on the cell, but they join

1 + 2 = 3

Synergistic influence

If both hormones are present, they have much greater effects

1 + 2 >> 3

Permissive hormone influence

A permissive hormone has little or no effect on its own

• Together with another hormone, it is “permitted” = exerts an effect on a cell

• 2 + 0 > 2

  • Permissive hormones only work if they have their pair

Antagonistic hormone influence

Hormones that have opposing actions

Ex: Insulin (synthesis of glycogen) and Glucagon (breakdown of glycogen)

3 Hormone types

1. Peptides

2. Steroids

3. Amines

Peptide hormones - key traits

• Made of multiple, linked amino acids

• Water soluble (because of the charges)

Examples of peptide hormones

Insulin and Glucagon

Steroid hormones - key traits

• Derived from cholesterol

• Lipid soluble (will interact with membranes)

Examples of steroid hormones

Estrogen, testosterone

Amine hormones - Key traits

• Derived from A SINGLE amino acid

• Some are water soluble, some are lipid soluble (depends on the amino acid)

Amine hormone examples

• Catecholamines = tyrosine derivatives (epinephrine, norepinephrine, dopamine) — water soluble

• Thyroid hormones = tyrosine (t3, t4) — Lipid soluble

• Melatonin = tryptophan derivative

Peptide hormone - Synthesis pathway

1. Protein is made on the rough ER = preprohormone

2. Signal sequence is cleaved = prohormone

3. Prohormone is sent to the Golgi, then to a secretory vesicle (**enzymes will cleave it into an active hormone)

4. Release signal = vesicles dump contents into the body/bloodstream

Examples of Peptide hormone processing:

1. The preprohormone encodes for multiple copies of a hormone

2. The preprohormone encodes for several different hormones

Peptide hormone post translational processing

Ex: Insulin is synthesized with C-peptide, which gets cleaved to activate insulin

• The C-peptide “junk” is more stable and survives longer, so we can study it better than insulin itself (a by-product of the reaction)

C-peptide Test

A measure of the amount of C-peptide, which has a longer duration than insulin

Peptide hormones have a _____ half-life

Very short

(usually = several minutes)

Peptide hormones are good at ________, but cannot ______

Good at traveling in fluids, but they cannot cross cell membranes

(remember—they’re water soluble)

Mechanism of action for Peptide hormones

Bind a surface membrane receptor → activate a 2nd messenger

1. Modify the existing proteins = effect is fast

2. Longer effects on other cell targets (influence transcription)

Insulin effect on the cell (molecular level)

Insulin signaling causes GLUT4 glucose transporters to traffic from internal vesicles to the cell membrane

Insulin is secreted when …

Blood glucose concentration increases

Effect of insulin on cells

• Unique effects on different cells

  • Promotes the uptake of glucose in skeletal muscle cells

Insulin is ____ _____

Tightly regulated

• Because there are major consequences if there isn’t enough glucose in the blood (esp. for the brain)

• Half-life in plasma = 4-6 mins

Steroid hormone synthesis

• Made in specific organs: adrenal cortex, skin, placenta, gonads

• Made in the smooth ER (think lipid)

  • Made from cholesterol in an ON DEMAND fashion — none stored

Describe circulation of steroid hormones in the bloodstream

Because they’re lipid soluble, steroid hormones use a transport protein to move through the bloodstream

Steroid Hormone : “free fraction”

Used to describe how 0.1-10% of lipid-soluble hormones are not bound to the transporter because they must dissociate for a short period of time in order to bind the receptor

Steroid hormone receptors

1. Cell surface receptors (triggers a cascade and effect)

2. Cytoplasmic receptors

3. Nuclear receptor — MOST diffuse and go to the nucleus = have effects on TXN (major alteration to cell behavior)

Estrogen

Steroid hormone — Induces growth (breast growth, pubic and underarm hair, widening of the pelvis)

Steroid hormones are made on demand. Whare are they not made in advance and stored in secretory vesicles?

Because they’re lipid soluble = cannot be contained in vesicles - they just diffuse out

Why do naturally produced steroid hormones have a long half-life compared to the 5-10 minutes for peptide hormones?

Because steroid hormones are protected from degradation by their solute carrier

(The carrier acts like an invisibility cloak)

Why is prolonged insulin dangerous to the body

Because the brain needs a constant supply of glucose

2 Tyrosine derivatives - Amine hormones

1. Catecholamines

2. Thyroid hormones

Catecholamines

• Tyrosine-derived amine hormones

• Made in advance and stored in vesicles

  • Act like peptide hormones (water soluble)

Thyroid hormones

• Tyrosine-derived amine hormone

• Immature forms of T4 and T3 are stored then processed on demand

  • Act like steroids (lipid soluble)

What is the tryptophan derived amine hormone

Melatonin

Melatonin

Derived from tryptophan

• Made and released cyclically (not stored)

• Act like peptide hormones

What composes the Endocrine central command

Hypothalamus, Anterior Pituitary, Posterior Pituitary

• Links the endocrine and nervous system

Infundibulum

The connecting stalk between hypothalamus and the pituitary

The Hypothalamus secretes (2 bullets)

1. 6 main hormones that regulate the anterior pituitary hormone secretion

2. 2 other hormones and stores in the posterior pituitary

Anterior Pituitary

5 resident cell types make hormones

Posterior Pituitary

• Extension of neural tissue

• Hormone storage

Pathway between the Hypothalamus and the Posterior Pituitary

1. Neuron makes “neurohormone” (in hypothalamus)

2. Vesicles are transported down the axon

3. Vesicles stored in the posterior pituitary

4. Vesicles are released to the blood — triggered by an A.P and Ca2+

KEY POINT = DIRECT RELEASE TO BLOOD

What are the 2 hormones made in the hypothalamus-posterior pituitary pathway

1. Oxytocin

2. Anti Diuretic Hormone (ADH)

Oxytocin function

• Smooth muscle contraction

• Milk ejection

Anti Diuretic Hormone (ADH) function

• Decrease the water in the urine

The hypothalamus commands the ____ ____ …. … ….

Commands the anterior pituitary, which talks to a lower level endocrine glands

• Levels of control

Describe the process of anterior pituitary control by the hypothalamus

1. Secretory neurons (hypothalamus) make releasing and inhibiting hormones

2. Hormones ride the portal system (capillaries)

3. Govern the anterior pituitary secretions

Portal System

2 sets of capillaries in a series connected by a set of small veins

• Allows movement of hormones in hypothalamus and pituitary

• Blood Brain Barrier Exception

Benefits to the hypothalamus-anterior pituitary communication

Efficiency — Short distance, speed, and you need less hormone

Risks to the hypothalamus-anterior pituitary communication

The hypothalamus and pituitary gland are exposed to circulation

What is example of an exception to the BBB in hormone secretion

The portal system

What are the 5 cell types in anterior pituitary

1. Somatotroph

2. Thyrotroph

3. Corticotroph

4. Lactotroph

5. Gonadotroph

Somatotroph

Secretes growth hormone

(Soma = broadly targeting the somatic cells/body)

Thyrotroph

Secretes thyroid stimulating hormone

Corticotroph

Secretes adrenocorticotropic hormone

Lactotroph

Secretes prolactin

Gonadotroph

Secretes 1. Follicle stimulating hormone AND 2. Luteinizing hormone

Growth Hormone (GH) — Stimulated/Suppressed by:

Stimulated: Growth hormone-releasing hormone

Suppressed: Growth hormone-inhibiting hormone

Thyroid-stimulating hormone (TSH) — Stimulated by:

Thyrotropin-releasing hormone (TRH)

Adrenocorticotrophic hormone (ACTH) — stimulated by:

Corticotrophin-releasing hormone (CRH)

Prolactin — Suppressed by:

Prolactin-inhibiting hormone (PIH) = dopamine

Follicle-stimulating hormone (FSH) — Stimulated by:

Gonadotropin-releasing hormone (GnRH)

Luteinizing hormone (LH) — Stimulated by:

Gonadotropin-releasing hormone (GnRH)

Growth Hormone (GH) has both _____ and _____ targets

Endocrine and non-Endocrine

Growth Hormone (GH) endocrine targets

Liver → make insulin growth factors (igf)

Growth Hormone (GH) non-endocrine targets

1. Bones

2. Other Connective Tissues

3. Muscles

Growth Hormone (GH) effect

Promote cell growth (Both in proliferation and increasing cell sizes)

Growth hormone stimulates the proliferation of ______ and the 2 kinds =

Mesenchymal cells = Chondrocytes and Osteoblasts

Chondrocytes

Produce cartilage

Osteoblasts

Produce bone

Growth Plates

Epiphyseal plates on the ends of long bones

• Ordered columns of chondrocytes that will be replaced by bone (from osteoblasts)

Dwarfism

Hyposecretion of GH

Giantism

Hypersecretion of GH - in youth, while the long bones are still growing

Acromegaly

Hypersecretion of GH - continued into adulthood

• Result = affects subset bones (hands, feet, jaw)

Thyroid gland major function

Increase the Basal Metabolic Rate (BMR) = rate of energy expenditure

Basal metabolic rate (BMR)

The rate of energy expenditure

3 Components that control basal metabolic rate (BMR)

1. Rate of cellular respiration

2. Increase in the mitochondrial number

3. Impact of thermogenesis — metabolic function can elevate body temp

Follicular cell

In thyroid

• Use iodine to produce amine hormones: T4 and T3

  • Immature versions of these hormones are in the “colloid” = lumen of the follicle

Where are T3 and T4 produced

In the Thyroid follicular cells

Thyroid Hormone secretion regulation (the cycle)

1. Low blood T3 and T4 stimulates the hypothalamus to release: thyrotropin releasing hormone (TRH)

2. TRH travels the portal veins = causes the release of thyroid stimulating hormone (TSH)

3. TSH stimulates T3 and T4 production

4. Negative Feedback — T3 and T4 inhibit TRH and TSH release

Hyperthyroidism (+ the 4 symptoms)

(Grave’s disease)

Excess production of T3 and T4

• Abnormally high BMR

• Weight loss, increased appetite

• Sweating

• Sensitivity to heat

Hypothyroidism

Deficiency in thyroid hormone production

• Abnormally low BMR

• Fatigue

• Weight gain, low appetite

• Low body temperature

• Sensitivity to low temperatures

Parafollicular cells

In thyroid — live between the follicles (outside the follicular cells)

• Secrete the hormone calcitonin

Calcitonin

• Produced by parafollicular cells

• Regulates blood Ca2+ levels

• Inhibits osteoclasts = cells that breakdown bone

• THEREFORE — they lower blood Ca2+ by inhibiting bone breakdown

Parathyroid gland

Secretes parathyroid hormone