exam 2

Autocrine vs. Paracrine Signals

Autocrine Signals: release signaling molecule into extracellular space and binds receptor on same cell

Paracrine Signals: secreted by one cell and diffuse to adjacent cells

Neurotransmitters

chemicals secreted by neurons that diffuse across a small gap to target cell and synaptic cleft (space between neurons at nerve synpase) is observed

Neurohormones

chemicals released by neurons into blood for action at distant targets

Four Categories of Membrane Receptors

Receptor or Ion-Channeled (ligand-gated)

G Protein-Coupled Receptors: regulates proteins involved in information transfer pathway

Two Catalytic Receptors:
1. Receptor-Enzyme: ligand binding activates an intracellular enzyme
2. Integrin Receptor: ligand binding to integrin

What is an amplifying cascade?

Activation of signal protein until a substrate is converted to a product (mediated by kinases)

What is Signal Amplification?

allows small amount of signal to have a large effect by activating enzymes that can activate second messenger molecules into more products

What effects do IP3 and DAG have?

IP3 mainly releases calcium from intracellular stores

DAG mainly activates protein kinase C and phosphorylates proteins

What are the steps of the GPCR-Adenylyl Cyclase Signal Transduction Pathway?

1. Bind G protein-coupled receptor (GCPR)
2. G proteins turn on amplifier enzyme adenylyl cyclase
3. Adenylyl cyclase converts ATP to cyclic AMP
4. cAMP activates protein kinase A
5. Protein kinase A phosphorylates other proteins leading to cellular response

What are the steps of the GCPR-Phospholipase C (IP3-DAG System) Signal Transduction Pathway?

1. Signal molecule activates receptor and G protein
2. G protein activates amplifier enzyme phospholipase C (PLC)
3 PLC converts phospholipids into DAG remaining in membrane and IP3 which diffuses into cytoplasm and binds to ligand-gated calcium channel receptor on endoplasmic reticulum
4. DAG activates protein kinase C (PKC) which phosphorylates proteins
5. IP3 causes release of calcium from organelles creating calcium signal

Agonist vs Antagonist

Agonist: sneaks and binds to receptors and gives response you want

Antagonist: blocks receptor activity and doesn't cause downstream response

Tonic Control (With Example)

regulates physiological parameters in an up-down fashion
Ex: decreased signal rate results in dilation of vessel and increased signal rate results in constriction of vessel

Antagonistic Control (With Example)

uses different signals to send a parameter in opposite directions
Ex: Parasympathetic Neuron slows down heart rate and Sympathetic Neuron speeds up the heart rate

Hormones as Cell-To-Cell Communication Molecules

chemical signals secreted by a cell or group of cells that's transported into the blood and acts on distant target tissue receptors

How do hormones modulate biochemical responses?

hormones alter enzyme activity, gene expression, protein synthesis, and ion/molecule transport across cell membrane

What are the two main ways hormone action can be terminated?

1. hormone broken down (molecular structure less active)
2. secrete/filter hormone by the kidneys

What are the 3 chemical classes of hormones?

peptide/protein hormones, steroid hormones, and amino acid-derived hormones

Compare the Half Life of the 3 Chemical Classes of Hormones

Peptide/Protein Hormones: short
Steroid Hormones: long

Amino Acid-Derived Hormones (Catecholamines): short
- exception is thyroid hormone with long half life

Location of Hormone Receptor at Target Cell of 3 Chemical Classes of Hormones

Peptide/Protein Hormones: cell membrane
Steroid Hormones: mainly cytoplasm or nucleus
Amino Acid-Derived Hormones (Catecholamines): cell membrane
- exception is thyroid hormone which has a nuclear receptor

Which chemical class of hormones needs a receptor on the outer surface of the membrane to pass through?

peptide/protein hormones because they are lipid insoluble

Which hormones are derived from the cholesterol molecule?

steroid hormones

What are the two amino acids that amino acid-derived hormones are derived from?

Tryptophan: melatonin in brain
Tyrosine: Catecholamines (epinephrine/dopamine) and thyroid hormones

What are the basic steps of protein synthesis?

1. DNA --> mRNA (Transcription)
2. mRNA leaves nucleus
3. mRNA --> synthesized peptides and proteins (Translation)

What is the importance of the Active Hormone in Peptide Hormone Synthesis?

peptide chain of prohormone folds back on itself with help of disulfide bonds to cleave two separate hormones
Ex: proinsulin --> insulin (controls blood glucose level) and C-peptide ("trash" molecule)

The 3 Pathways of Peptide Hormone Mechanism of Action

1. Receptor couples to G regulatory protein which opens ion channel that allows extracellular calcium to enter the cell.

2. Receptor couples to G regulatory protein to activate an amplifier enzyme which goes to the second messenger systems (mediates phosphorylation of key proteins in the cell) that phosphorylates proteins to create cellular response.

3. Receptor uses tyrosine kinase enzyme which directly alters phosphorylation of proteins to create cellular response.

Steps in Steroid Hormone Mechanism of Action

1. Hydrophobic steroids bind to plasma protein carriers.
2. Steroid hormones bind to receptors that use second messenger systems to create rapid cellular response.
3. Receptor-hormone complex binds DNA and activates/represses genes.
4. Translation produces new proteins for cell processes.

Why can't steroid hormones be stored like water soluble hormones?

Steroid hormones are lipid-soluble so must be quickly secreted whereas water soluble hormones have packaged secretory granules stored in inner gland for later secretion.

What is negative feedback?

a response to a change in the body that counteracts or opposes the initial change

What is the role of Exogenous Cortisol?

suppress endogenous cortisol, act on target tissues, and exert negative feedback on anterior pituitary and hypothalamus

Where is CRH produced and what is its job?

Produced in Hypothalamus

Sole job to act on anterior pituitary to synthesize/secrete ACTH

Where is ACTH produced and what is its job?

Produced in Anterior Pituitary

Regulates adrenal cortex and stimulates its growth by causing it to synthesize/secrete cortisol

Where is Cortisol produced and what is its job?

Produced in the Adrenal Cortex

Suppresses secretion of ACTH and CRH via negative feedback by feeding back to the anterior pituitary and hypothalamus

What is the general pathway in the secretion of cortisol?

CRH --> ACTH --> Cortisol --> target tissue --> cellular response

Synergism

combined effect is greater than the sum of individual effects
Ex: epinephrine and glucagon combined will significantly increase blood glucose levels

Permissiveness

need second hormone to get full effect and maintain homeostasis
Ex: cortisol as the permissive hormone in background for blood glucose regulation

Anatagonism

one hormone opposes the action of another
Ex: glucagon serves to raise blood glucose while insulin serves to lower blood glucose

What causes hypersecretion (excess) of a hormone?

1. tumors/exogenous treatment
2. negative feedback may lead to atrophy of adrenal and pituitary gland

What causes hyposecretion (deficiency) of a hormone?

1. decreased synthesis materials/atrophy of adrenal gland
2. absence of negative feedback leads to overproduction of trophic hormones (no cortisol --> high CRH and ACTH remains)

Where is the problem located in Primary Hypersecretion? How are the levels of CRH, ACTH, and Cortisol affected?

Problem in Adrenal Cortex

Increased levels of Cortisol and since negative feedback present, lowered levels of ACTH and CRH.

Where is the problem located in Secondary Hypersecretion? How are the levels of CRH, ACTH, and Cortisol affected?

Problem in Anterior Pituitary

Resistance to negative feedback in anterior pituitary means increased ACTH and cortisol but negative feedback exerted on CRH to lower its levels.

Where is the problem located in Tertiary Hypersecretion? How are the levels of CRH, ACTH, and Cortisol affected?

Problem in Hypothalamus

Resistance to negative feedback in hypothalamus leads to increased levels of CRH which is overdriven to cause increased levels of ACTH and Cortisol so negative feedback fails.

What is the structure of the Pituitary gland and which is the true endocrine gland?

Two glands with different embryological origins that fused and now sit in protected pocket of bone connected to brain by thin stalk

Anterior Pituitary is the true endocrine gland

Posterior Pituitary

extension of neural tissue and role as neurostorage organ

Anterior Pituitary

true endocrine gland of epithelial origin and has hormone synthesizing cells present

What are the two neurohormones the posterior pituitary stores/releases?

vasopressin and oxytocin

What are the two main roles of Vasopressin (ADH)?

1. regulates water excretion (concentration of urine) in kidneys
2. regulates vascular smooth muscle contraction in blood vessel walls

What are the two main roles of Oxytocin?

1. release of milk from breast during lactation/nursing (acts on mammary glands)
2. stimulates contraction of uterus in female (acts on uterus and initiates birth process)

What are the six hormones that the anterior pituitary secretes? Which 4 are trophic hormones and which 2 are direct-acting hormones?

Trophic Hormones: TSH, ACTH, FSH, and LH
Direct-Acting Hormones: Prolactin and Growth Hormone

What is the role of TSH?

regulate hormone synthesis/secretion in thyroid gland

What is the role of ACTH?

regulates hormone synthesis/secretion of steroid hormone cortisol and androgens (mainly cortisol) in the adrenal cortex

What is the role of FSH and LH?

gonadotropins that act on ovary or testes to regulate reproduction (stimulates development of sperm and egg)

What is the role of Prolactin?

milk production in females

What is the role of the Growth Hormone?

stimulates growth of bone and skeletal muscles and has metabolic effects on regulating glucose levels in adults

What two things can happens if TSH levels are in excess?

1. Goiter (abnormally large thyroid) as result of hypertrophy and seen in areas with deficiency in iodine
2. raise in metabolism so stimulated growth of gland

What is the hypothalamic releasing hormone of TSH?

TRH

What is the hypothalamic releasing hormone of ACTH?

CRH

What is the hypothalamic inhibiting hormone of Prolactin?

dopamine

What is the hypothalamic inhibiting hormone of Growth Hormone?

Somatostatin

Portal System

consists of two sets of capillaries connected in series by a vein

Hypothalamic-Pituitary Portal System

1. Hypothalamic neurons produce trophic hormones
2. Released into 1st capillary bed in portal system to anterior pituitary
3. Anterior pituitary endocrine cells produce trophic hormones
4. Released into capillary bed in pituitary leading to target tissues
5. Ensures small amount of concentrated hormone directed to target

Long-Loop Negative Feedback

Most dominant feedback mechanism in which peripheral endocrine gland produces hormone that suppresses secretion of anterior pituitary and hypothalamic trophic hormones (Ex: Cortisol suppresses ACTH and CRH)

Short-Loop Negative Feedback

pituitary hormone suppresses hypothalamic trophic hormone production (Ex: ACTH suppresses CRH via feedback to hypothalamus)

Ulta-Short-Loop Negative Feedback

occurs in hypothalamus and pituitary and requires autocrine/paracrine signals to regulate secretion (Ex: CRH feeds back on itself to regulate its own secretion)

Hormone Hyposecretion (Posterior Pituitary)

1. Hypothalamus fails to synthesize ADH leading to neurogenic (deficiency in ADH) diabetes insipidus (large volumes of dilute urine since kidney excreting max water amount)
2. Kidney fails to respond to ADH (nephrogenic diabetes insipidus)

Results in excess water excretion by kidney (dehydration)

Hormone Hypersecretion (Posterior Pituitary)

1. Exogenous source of ADH (pulmonary (lung) tumors)
2. Excessive uncontrolled secretion of ADH

Results in excess water retention by kidney (water intoxication)

Hormone Hyposecretion (Anterior Pituitary)

Caused by:
1. anterior pituitary cell activity (single or multiple cell types)
2. absence of hypothalamic neurosecretory neuron activity
3. damage to endocrine gland

Hormone Hypersecretion (Anterior Pituitary)

Caused by:
1. anterior pituitary (trophic hormones) cell activity/tumor (single/multiple cell types)
2. excess activity of hypothalamic neurosecretory neurons

Adrenal Gland

Sits atop kidneys and is multi-layered. Composed of the adrenal cortex and adrenal medulla.

Adrenal Cortex

thick outer later with three separate regions (is a true endocrine gland secreting steroid hormones)

Adrenal Medulla

core that is its own separate gland producing epinephrine (secretes catecholamines)

What are the three zones of the adrenal cortex?

zona glomerulosa, zona fasciculata, and zona reticularis

What is the role of the Zona Glomerulosa?

Secretes Aldosterone
Regulates sodium secretion in kidney

What is the role of the Zona Fasciculata?

Secretes Glucoccorticoids
Thickest later that regulates intermediate metabolism

What is the role of the Zona Reticularis?

Secretes Sex Hormones
Produces DHEA (a weak androgen that many have minor metabolic effects helping mediate sexual development during puberty)

What is always the 1st step (rate-limiting step) of adrenal steroid biosynthesis?

cholesterol --> pregnenolone

What is the adrenal steroid biosynthesis pathway for Zona Glomerulosa?

cholesterol --> prognenolone --> progesterone --> aldosterone

What is the adrenal steroid biosynthesis pathway for Zona Fasciculata?

cholesterol --> prognenolone --> progesterone --> oh-progesterone --> cortisol

What is the adrenal steroid biosynthesis pathway for Zona Reticularis?

cholesterol --> pregnenolone --> DHEA

What are main global effects of cortisol on the body?

1. Promotes gluconeogenesis (makes new glucose) and glycogenesis (makes new glycogen) in the liver
2. Stimulates protein catabolism (breakdown to amino acids) that fuels gluconeogenesis
3. Enhances lipolysis (break down fats) so fatty acids can provide alternate energy to peripheral tissues

What happens when cortisol levels rise?

1. Suppressed immune system and inhibited inflammation
2. Cause negative calcium balance (increased excretion/bone resorption) which can lead to osteoporosis
3. Influences brain function

4 Main Targets of Cortisol Secretion

1. Immune System (Function Suppressed)
2. Liver (Gluconeogenesis)
3. Muscle (Protein Catbolism)
4. Adipose Tissue (Lipolysis)

Cortisol as an Immunosuppressant

1. inhibits immune system function
2. helps prevent rejection of transplanted organs

Cortisol as an Anti-Inflammatory Agent

1. suppresses inflammatory responses (promotes healing)
2. used for treating bee stings, poison ivy, and arthritis (inflammation in cartilage/joints)

What is primary hypercortisolism?

An adrenal tumor that autonomously secretes cortisol

What is secondary hypercortisolism? What disease is associated with this?

a pituitary tumor that autonomously secretes ACTH (Cushing's Disease)

What is tertiary hypercortisolism?

a peripheral (lung) tumor that autonomously secretes ACTH

_____________ (Physician-Caused) Hypercortisolism

Iatrogenic

What is primary hypocortisolism? What disease is associated with this?

hyposecretion of all adrenal steroid hormones so secretes both cortisol and aldosterone so kidney can maintain sodium and blood pressure (Addision's Disease)

What is secondary hypocortisolism?

hyposecretion of cortisol but not of aldosterone

What does Cushing's Syndrome cause?

diabetes mellitus due to abnormally high blood glucose

What are the four major symptoms of Cushing's Syndrome?

1. Moon Face (red cheeks due to retention of excess fluid and sodium)
2. Abdominal Fat with Striations (fat deposits in trunk and dark striations result from protein breakdown in skin)
3. "Buffalo Hump" (fat deposition above clavicle/neck)
4. Spindly arms/legs

Thyroid hormones are made from amino acid ____________, is a "_______ ___________" hormone, and is the primary hormone regulating ______ ______________.

tyrosine; long acting; body metabolism

Synthesis of thyroid hormone takes place in the __________ _________ that have a center filled with "jelly-like" ________ that holds great supply of hormone.

thyroid follicles; colloid

What is the role of thyroglobulin in the follicle cells?

backbone for storage of thyroid hormone

1. I + Tyr = ?
2. I + MIT = ?
3. I + DIT / MIT + DIT = ?
4. DIT + DIT = ?

1. monoiodotyrosine (MIT)
2. diiodotyrosine (DIT)
3. T3 (the most active thyroid hormone)
4. T4 (which is mostly secreted by thyroid gland)

What are C Cells of Thyroid Gland?

cells that secrete calcitonin and are a separate endocrine gland not related to energy metabolism

Thyroid Hormone Synthesis Steps

1. Na+-I- symporter brings I- into cells and moves I- into colloid.
2. Follicular cell synthesizes enzymes and thyroglobulin for colloid.
3. Thyroid peroxidase couples iodine to tyrosine to make T3 and T4.
4. Thyroglobulin is taken back into the cell in vesicles.
5. Intracellular enzymes separate T3 and T4 from protein.
6. Free T3 and T4 enter circulation and diffuse into the bloodstream.

Hyperthyroidism

causes gland to hypertrophy and produce more thyroid hormones (secretes too much hormone)

Graves' Disease

autoimmune disease where antibodies directed against TSH (elevated levels of T3 and T4)

Exophthalmos

eyeball bulges outward due to inflammatory process within eye socket and deposition of mucopolysaccharides behind eyeball

Other Impacts of Hyperthyroidism

1. increases oxygen consumption and metabolic heat production
2. increase protein catabolism (may cause muscle weakness)
3. Hyperexcitable reflexes and physiological disturbances
4. Influence B-adrenergic receptors in heart (overexpression --> oversensitive to catecholamines in heart --> overbeating)