Endocrine, Nervous, Autonomic Physiology

Week 2

Define Hormone, Target Cells

Helps regulate body metabolism, growth, and reproduction

• Target cells: Carried to target cells having receptor proteins for those specific hormones

  • Specific Binding

Define Neurohormones.

Secreted by specialized cells of the hypothalamus

What are the two broad classes of Hormones?

1. Amino Acid Derived (Amine, Peptide, Protein Hormones)

2. Lipid Derived (Steroid Hormones)

Amino Acid Derived

Polar → Hydrophilic → Not permeable

Binds to receptor on cell membrane (2nd Messenger Pathway)

Amine

Single amino acid modified to form a hormone. (Tyrosine + Tryptophan)

• Tryptophan - Melatonin

• Tryptophan - Catecholamines

  • Norepinephrine

  • Epinephrine

  • Dopamine

  • *Thyroid Hormones (acts like a lipid hormone)

Peptide

Multiple Amino Acids linked to form an amine acid chain

• Oxytocin - Child birth

• ANP - Hormones from the heart

• ADH - Kidneys

Protein Hormone

Longer Polypeptide Chain

• GH

• FSH

Lipid Derived Hormones

Non-Polar → Hydrophobic → Permeable to cell membrane

Binds to receptor in cytoplasm

Affects DNA

(Requires Transport Proteins in Blood)

(Cholesterol)

Lipid Derived Hormones Example

Testosterone, Estrogen

Aldosterone, Cortisol

Hormone Receptor Interaction

Receptors are proteins on the cell membrane or inside the cell (Changed Function of Cell)

Very Specific

Changes that might happen within the cell

• Protein Synthesis, activation, deactivation of enzymes

• Alteration of permeability

• Altered rates of mitosis, cell growth, and stimulation

Which class will use the 2nd Messenger Pathway

Amino Acid Derived Hormones (Except for Thyroid Hormones)

Adenylate Cyclase Pathway

1. Hormone Binds to receptor and trigger G proteins to dissociate

2. G proteins attach to Adenylate Cyclase

   1. Converts ATP to CAMP

3. CAMP will attach to regulatory Subunit attached to inactive protein kinase and removes regulatory subunit.

4. Inactive protein kinase is then Activated → (Activation of inactivation of enzymes)

**Polar Hormones Will Use**

Phospholipase C Pathway

1. Hormone binds to receptor and Alpha Subunit will dissociate and bind to Phospholipase C

2. Membrane phospholipid will split into DAG and IP3

   1. DAG will activate protein kinase which will alter cell phsiology

   2. IP3 Will target endoplasmic reticulum with Ca2+ which will release calcium into cytoplasm

      1. Ca2+ will bind to calmodulin

      2. Activates protein kinases which will alter cell physiology

Epinephrine use of both Pathways

1. Epinephrine attaching to receptor making ATP to CAMP activating active protein kinase

2. Glycogen will become glucose and blood glucose will rise

OR

1. Epinephrine will attach to receptor making Ca2+ to turn to bind to calmodulin activating protein kinase

2. Glucose will increase blood glucose levels

Hormones are taken as drugs at high concentration

May result in binding to receptors of related hormones causing side effects

Upregulation

Hormones bind to receptors from BV’s. Vesicles w/ Receptor will fuse to cell membrane creating more receptors

Downregulation

BV’s supply with too much hormone and cell doesn’t have enough receptors.

Causing desensitization, and signaling becomes weak

Synergetic Hormones

When 2 Hormones w/ Similar effects produce an amplified response.

Ex: 2 different reproductive hormones: FSH from ANT PIT and Estrogen from ovaries are required to for the maturation of eggs

Permissive Hormones

1 Hormone works better because of another hormone

Ex: Thyroid hormone having a complex permissive relationship w/ certain reproductive hormones

Antagonistic Hormones

2 Hormones have opposing effects

Ex: Insulin and Glucose

Master regulator of the endocrine system

Hypothalamus

*Both Neural and Endocrine functions

Hypothalamic Hormones: Releasing + Inhibiting Hormones

Releasing + Inhibiting Hormones

Releasing: CRH, GNRH, TRH, GHRH, PRH

Inhibiting: GHIH (Somatostatin), PIH (Dopamine)

Hypothalamohypophyseal Portal System

Hypothalamus will send hormones through a capillary bed to the Anterior Pituitary Gland which will secrete hormones into BVs and go all over the body and target cells.

CRH becomes…

ACTH → Glucocorticoids Cortisols in cortex, and Adrenal Androgens in Adrenal Cortex.

GNRH becomes…

FSH, LH → Ovaries + Testes = Gamete Production

TRH becomes…

TSH → Thyroid gland to thyroid hormones

GHRH becomes…

GH → Different tissues to overall growth

PRH becomes…

Prolactin → mammary gland to milk production

GHIH and PIH

1. Somatostatin

Stops growth hormone

2. Dopamine

Stops prolactin secretion

Hypothalamohypophyseal Tract

ADH and Oxytocin fro the hypothalamus, and moves down the axon to the Posterior Pituitary Gland and released ADH and Oxytocin to BVs

ADH + Oxytocin

ADH: Water retention from kidneys, decreased Urination

Oxytocin: Milk secretion, Labor Contractions

In males gives feeling of love, closeness, and sexual response

Acromegaly, Gigantism, Dwarfism

Acromegaly: Excess Secretion of GH in Adulthood

Gigantism: Excess Secretion of GH in childhood

• Can be stopped with somatostatin

Dwarfism: Inadequate Section of GH in childhood

• Can be treated w/ Recombinant GH

Thyroid gland

Secretes T3, T4 (Produced from the follicles), and calcitonin (produced by Parafolllicular Cells)

Thyroid Hormone Production

Iodide in plasma → peroxide → Thyroglobulin becomes MIT and DIT. MIT + DIT = T3, DIT + DIT = T4 → goes to BVs

Functions of thyroid hormone

• Stimulates protein synthesis

• Promotes maturation of nervous system

• Increases rate of cellular respiration

• Elevates basal metabolic rate

Function of Calcitonin

Lowers blood calcium levels

Parathyroid Hormone that increases blood calcium levels

How can iodine deficiency lead to goiter?

Hypothalamus releases TRH → Pituitary gland releases TSH → Thyroid Gland releases T3 + T4.

Goiter bombards thyroid with TSH as TRH and TSH production increases, because there isn’t enough to repopulate the receptor.

HPT Pathway

Hypothalamus releases TRH → Pituitary gland releases TSH → Thyroid Gland releases T3 + T4.

T3 + T4 send receptor to reduce TSH and TRH

How blood calcium levels are regulated by calcitonin and parathyroid hormone

Increased Ca2+ in blood → Calcitonin release from parafollicular cells → Bones aborb more Ca2+ OR Kidneys pee more Ca2+ = Ca2+ levels reduce

Parathyroid H

Lowered blood Ca2+ → PTH gland releases PTH → Bones increased dissolving OR kidenys absorb more Ca2+ OR intestines absorb more Ca2+

Adrenal Gland

Located on top of the kidneys

• Adrenal Cortex

• Adrenal Medulla

Adrenal Cortex Horomones

Mineralocorticoids, Glucocorticoids, Adrenal Androgens

Mineralocorticoids

Regulate mineral Balance - Aldosterone

Increase sodium resorption from kidney tubules back to blood

Tissue Area: Zona Glomerulosa

Glucocorticoids

Regulate metabolism - Cortisol, Corticosterone, Cortisone

Regulate glucose metabolism

Zona Fasciculate

Adrenal Androgens

Stimulates masculinization - Dehydroepiandrosterone

Weak sex hormones that supplement those made in gonads

Zona Reticularis

Adrenal Medulla

Epinephrine + Norepinephrine - Amine - Stimulates fight or flight

Stress hormones released (stimulates sympathetic ANS)

HPG Pathway

Hypothalamus releases GnRH → Anterior pituitary releases FSH LH → Gonads → Sex steroid hormones

• If enough stops producing

Pancreas

Exocrine and endocrine

Endocrine cells: Alpha cells, beta cells

Type 1 Diabetes

Caused by destruction of beta cells resulting in lack on insulin secretion

Type 2 Diabetes

Insulin resistance, or decreasing tissue sensitivity to the effect of insulin

Pineal Gland

Inferior and posterior to thalamus

Secretes Amine hormone Melatonin

Influences circadian rhythm

• Innervated by sympathetic nervous system

Jet lag

Time zones may disturb the light-dark cycle

GI Tract

Gastrin, Secretin, cholesytokinin

Heart

ANP (Atrial Natriuretic Peptide)

Kidneys

Renin, Calcitriol, Erythropoietin

Estrogen

Stimulates development of secondary Sex Characteristics and prepare the body for child birth

Testosterone

Stimulates development of secondary sex characteristics and sperm production

HCG

Promotes progesterone syntheses during pregnancy and inhibits immune response against fetus

Autocrine and Paracrine signals

Autocrine: The sender and receiver are the same cell type

Paracrine: The sender and receiver are different cell types/tissues

Nitric oxide

Site: Endothelium of BVs

F: BVs dilation

Endothelin’s

Site: Endothelium of BVs

F: BV’s Constriction

Prostaglandin

Site: Various tissues of the body

F: Local regulators, Promotes inflammation, pain, fever, ovulation, uterine contractions, gastric secretions, blood clotting, etc….

Resting Membrane Potential

When the neuron is at rest

-70 Mv

All living cells have a RMP

What ions are present in higher concentration outside the neuron compared to inside

Higher outside: Na+ Cl-, Ca2+

Higher Inside: K+

Why is the inside of the neuron negative

• Sodium Potassium Pump: 3Na+ out 2K+ in (Deficit in positive charge)

• Potassium Leak Channels: Membrane to permeable to potassium at rest.

• Negatively charged proteins inside the cell

Current

Movement of charge

Potential Difference

Separation of charge

Resistance

Something that prevent charge to move

Conductance

Something allows charge to move

Excitable Cells of the Body

Neurons, MM cells, Glands

Depolarization

When the membrane potential inside the cell increases (Becomes move positive). Occurs when ions enter the cell (Usually Na+)

• VG Na+ Opens (Positive Feedback loop)

• VG K+ Closed

-55 to +30

Repolarization

A return to resting potential.

• VG K+ Open

• VG Na+ Fully closed

+30 to -70

Hyperpolarization

When membrane potential inside the cell decrease (Becomes more negative). Occurs when positive ions leave the cell (Usually K+) or negative ions (Cl-) enter the cell.

• VG K+ Open

• VG Na+ Closed

-70 to -85

Is Depolarization/Hyperpolarization Excitatory or Inhibitory

Depolarization: Excitatory

Hyperpolarization: Inhibitory

Ligand Gated

Located: Cell Body

Neurotransmitters bind to it and open the gates allowing Ions to go in or out

Voltage Gated Sodium and Potassium Channels

Located: Axon + Axon Terminals

Open and closes in response to the changes in the membranes potential

Voltage Gated Calcium Channels

Located: Axon Terminals

Trigger and release neurotransmitters

Na+/K+ Pump

Located: Everywhere

Always active to maintain RMP

Gated

Na+ and K+ Leak Channels

Located: Everywhere

Always open to maintain RMP

Non-gated

Voltage Gated Sodium/potassium Channels

Sodium: 2 gates

• Open, Closed, Inactive (Ball and chain)

Potassium: 1 Gate

• Open, Closed (during RMP)

Electrical Synapse

Ions moving through cell gap junctions

• Occur in SM MM, and Cardiac MM

Chemical Synapse

The release of neurotransmitters from the axon terminal buttons. Travel through a Synaptic Cleft

Graded Potential

Results in opening of chemically regulated ion channels (also called ligand gated ion channels)

Graded Potential - Na+

ESPS - The neuron becomes more positive

Graded Potential - K+

IPSP - The neuron becomes more negative

Graded Potential - Ca2+

ESPS - The neuron becomes more negative

Graded Potential - Cl-

IPSP - The neuron becomes more negative

Temporal Summation

When one neuron gives another neuron tons of information

Spatial Information

When multiple neurons gives a singular neuron tons of information

Absolute / Relative Period

Absolute: No new action potential can be generated

Relative: A second action potential is possible

All or none

Threshold must reach -55mv or there will not be a action potential.

Stimulus Intensity

The size of the stimulus will not affect the size of the action potential. It will always reach +30mv

Cable Properties

Conduction is slower in the axon because so many action potentials are generated.

Myelinated and non-myelinated axon: Myelin provides insulation improving speed of cable properties

Amplitude

Amplitude of each action potentials remains the same

Saltatory conduction

When action potential leaps from node to node.

A fast conduction

Factors that increase the speed of conduction of an Action Potential

• Increased Diameter: reduces resistance to the spread of charges via cable properties

• Myelination