Endocrine System

A Hormone

A secreted molecule that travels through the blood to target cell(s), exerts some effect based on interaction with receptor. Can also act as a neurotransmitter

Neurotransmitters

Specifically act on target cells through synaptic cleft (a very small space). Can also act as a hormone.

Key Features of Hormones

- Name of hormone

- Type of molecule (e.g. steroid, peptide) and solubility (water or lipid)

- Cell type that produces hormone

- Stimulus for secretion

- What's the receptor (key properties of receptor)

- What effect does the hormone have? (biological effects)

Endocrine System

This system along with the nervous system are two main physiological control systems. Has roles in widely varying physiological functions such as homeostatic regulation of ions, energy availability, and coordinated changes such as growth and development

Which type of signal probably typically affects more target cells?

A typical hormone signal

Neural Signal

One cell communicates to target cell(s) via small gaps between cells called synapses. Fast, specifically targeted, shorter in duration

Endocrine (hormone) Signal

Endocrine gland secretes hormone into blood, which then travels to target cells. Slower, longer in duration, more widespread than neural signals. If being transported in the blood, it can reach a lot of target cells

Endocrine Glands and Organs that Secrete Hormones

Hypothalamus, Pituitary Gland, Pancreas, Kidney, Adrenal Gland, Thyroid and Parathyroid Glands, Ovaries, and Testes

Examples of Stress

- Psychosocial stress

- Temperature stress (hot or cold)

- Fasting

- Exercise

- Could all think of as threats to homeostasis

Adrenal Gland

Releases several hormones. Cortisol is released from outer layer (cortex) vs norepinephrine and epinephrine from inner layer (medulla)

CRH and ACTH

Both water-soluble peptide hormones that bind to g protein-coupled receptors

Cortisol

A lipid-soluble steroid hormone. It limits its own release.

Which is the best description of cortisol receptors?

Cortisol receptors are cytoplasmic receptors that enter the nucleus and act as transcription factors when bound to cortisol. This is because Lipid-soluble = Membrane-permeable and find cytoplasmic/nucleus receptors in order to act as transcription factors.

Physiological Effects of Cortisol

- Stimulation of liver cell uptake of amino acids and conversion to glucose

- Stimulation of triglyceride breakdown in adipocytes

- Inhibition of inflammation (Ex. Get injured during a physical activity but don't feel it till afterwards à Inflammation not inhibited anymore so can feel pain

- Inhibition of nonessential functions (e.g. growth and reproduction)

What effect would you predict insulin to have on plasma glucose levels?

Increase in plasma glucose levels

Interstitial Space/Interstitium

Fluid-filled extracellular space within a tissue

Plasma

Liquid (non-cellular) part of blood

Insulin

A major hormone regulator of the absorptive state, a period of time after a meal when ingested nutrients enter the blood

Glucagon

A major hormone regulator of the post-absorptive state, after the GI tract is no longer absorbing nutrients, when the body's own energy stores become the source of nutrients

For most cells, K+ is more concentrated where?

In the cytoplasm

How do beta islet cells function as a sensor?

They sense glucose levels indirectly by sensing an increase in ATP produced via metabolism

Why does glut2 facilitate transport into liver cells and out of liver cells in different physiological contexts?

Because it facilitates diffusion, and glucose concentration gradient varies

Insulin Homeostatic Regulation of Plasma Glucose Levels

1. Increased plasma glucose is sensed by beta islet cells in the pancreas in a mechanism involving metabolism, ATP production, and ATP-sensitive K+ channel

2. Exocytosis of insulin via voltage-gated Ca2+ channels

3. Insulin reduces plasma glucose levels by increasing glucose uptake by muscle and fat cells via glut4 exocytosis

and increasing production of glycogen from glucose in liver cells

Glucagon Homeostatic Regulation of Plasma Glucose Levels

1. Decreased plasma glucose is sensed by alpha islet cells in the pancreas (we are not defining mechanism)

2. Low plasma glucose leads to glucagon exocytosis

3. Glucagon increases plasma glucose levels by increasing production of glucose from glycogen in liver cells (Glucose production dries glucose transport out of cells down their concentration gradient via glut2)

Diabetes Mellitus

1. Plasma levels of glucose remain very high (what it's regulated by)

2. Type 1: Problem with beta islet cells (common cause is auto-immune disease): Little to no insulin produced (high levels of plasma glucose and low insulin levels due to beta islet cells being low/destroyed)

3. Type 2: Insulin insensitivity in skeletal muscle, adipocytes and/or liver cells (high levels of plasma glucose and insulin)

Why Regulate Ca2+?

Ca2+ is crucial for a lot of processes, including these examples:

1. Insulin release

2. Parathyroid hormone signaling

3. Neuronal signaling

4. Muscle contraction

Homeostatic Regulation of Ca2+ Involves?

The Parathyroid Glands, Bones, Kidneys, and GI Tract

Parathyroid Gland

The cells express a transmembrane receptor called calcium-sensing receptor (CaSR)

CaSR

A GPCR receptor. Ca2+ can't cross the membrane by itself so needs a transmembrane protein to sense it. Ca2+ binding to this receptor initiates a pathway that inhibits parathyroid hormone (PTH) release.

PTH

A water-soluble peptide hormone that binds to a GPCR. Its receptor activation activates Adenylyl Cyclase/cAMP/PKA pathway and Phospholipase C pathway (a key enzyme)

Osteoclasts

Break down calcified extracellular matrix in bone tissue, which releases Ca2+ into blood plasma

PTH Effects these Parts of the Kidney

Kidney Epithelial Cells and Endocrine Cells

PTH Effects on Kidney Epithelial Cells

PTH binds PTH receptor on epithelial cells to increase Ca2+ reabsorption by the kidney back into blood from urine that's being processed

PTH Effects on Endocrine Cells

PTH stimulates release 1,25 dihydroxy vitamin D (1,25(OH)2D), a lipid soluble hormone that acts on receptors in the intestine to increase Ca2+ absorption. Note that addition of two OH groups activates Vitamin D

1,25(OH)2D

A lipid-soluble hormone. It binds a receptor inside of target cells, causing movement of hormone-receptor complex into nucleus to stimulate transcription of target genes

Which of the following is an actuating signal, or part of an actuating signal in a negative feedback loop?

Parathyroid Hormone (PTH)

Low levels of a controlled variable stimulate the release of which hormone?

Glucagon and Parathyroid Hormone

Recap of Homeostatic Ca2+ Regulation

1. CaSR binding to Ca2+ in parathyroid gland cells initiates signaling that prevents PTH exocytosis (release). When Ca2+ is low, this inhibition is relieved, so PTH is released

2. PTH activity increases plasma levels of Ca2+ by increasing osteoclast activity which breaks down bone tissue, releasing Ca2+ into blood. Also by stimulating Ca2+ reabsorption in distal tubule and collecting duct in kidney nephrons. And by stimulating release of 1,25(OH)2D from the kidney, which binds to an intracellular receptor and stimulates transcription of TRPV6, a Ca2+ channel that increases Ca2+ absorption from intestinal lumen.

Stress Response/Pathway

Neural Inputs (stress) --> Hypothalamus (Corticotropin releasing hormone (CRH) released) --> Anterior Pituirary (Adrenocorticotropic Hormone (ACTH) released which is dumped into the bloodstream) --> Adrenal Cortex (Cortisol [The delivery point]) --> Many if not most tissues (respond to cortisol (stress response))

Insulin and Plasma Levels of Glucose Loop

Controlled Variable: Plasma Levels of Glucose

Sensor: Beta islet cells in pancreas (sensitive to high plasma glucose levels)

Controller: Beta islet cells in pancreas

Actuating Signal: Insulin

Effectors: Skeletal muscle, Adipocytes (fat cells), Liver cells

Beta Islet Cells as Sensor and Controller

High plasma glucose levels drives glucose transport via Glut2 (transmembrane protein) into beta islet cells --> Glucose --> Metabolized to ATP --> ATP binding to K+ channel (Binding closes the channel, blocking K+ flow out of cell. Also effects how the cell behaves so behavior depends on this) --> Voltage-gated Ca2+ Channels (Inside of cell gets more (+) in charge, opening up the voltage-gated channels --> Insulin --> Exocytosis releases insulin into blood

Effect of Insulin on Effector Cells (Muscle and Adipocytes)

Insulin binds to Insulin Receptor (Insulin is a water-soluble peptide hormone that binds a transmembrane receptor. The receptor is part of a class called receptor tyrosine kinases) --> Glut4 (transporter) --> Exocytosis to another Glut4 (Insulin stimulates Glut4 exocytosis and therefore increases glucose uptake. When insulin levels are low, Glut4 endocytosis is favored, reducing membrane permeability to glucose

Insulin Receptor

A Receptor Tyrosine Kinase:

Activated Tyrosine-Kinase Regions (Unphosphorylated Dimer) --> ATP to 6 ADP --> Fully Activated Receptor Tyrosine-Kinase (Phosphorylated Dimer) --> Inactive Relay Proteins bind to the phosphorylated tyrosine's and become activated and then release cellular responses

Effect of Insulin on Effector Cells (Liver Cells)

Insulin binds to Insulin Receptor --> Glycogen production from glucose (Glycogenesis). Glucose passively transports through Glut2 (Glut2 exocytosis/endocytosis not under hormonal control)

Glucagon and Plasma Levels of Glucose Loop

Controlled Variable: Plasma levels of glucose

Sensor: Alpha islet cells in pancreas (sensitive to low plasma glucose levels)

Controller: Alpha islet cells in pancreas

Actuating Signal: Glucagon

Effector: Liver cells

Effect of Glucagon on Effector Cells (Liver Cells)

Glucagon binds to Glucagon Receptor (Glucagon is a water soluble peptide hormone that binds a g protein-coupled transmembrane receptor --> cAMP increases --> Glucose from glycogen (Glycogenolysis) [Stimulates the breakdown of glycogen into glucose molecule] --> Glucose passively leaves cell through Glut2 (Glut2 endocytosis/exocytosis not under hormonal control (it's just there))

Negative Feedback Control of Plasma Ca2+

Controlled Variable: Plasma levels of Ca2+

Sensor: Parathyroid Gland cells via CaSR (Low Ca2+ levels cause these cells to release more hormone)

Controller: Parathyroid Gland (Sensor too)

Actuating Signal: PTH

Effectors: Bone, Kidney Epithelial Cells, [Kidney Endocrine Cells --> 1,25(OH)2D --> Intestine]

Effect of 1,25(OH)2D on Intestinal Epithelial Cells

1,25(OH)2D --> Vitamin D receptor (VDR) --> TRPVG transcription (binding activates this) --> TRPV6 is a Ca2+ channel that allows Ca2+ to enter. [All taking place in the intestinal lumen]