Endocrine 1: intro

Question 1

What are hormones and what kind of cells are they produced by?

Answer 1

Chemical messengers, produced and released by non-neural endocrine cells or neurons, which regulate activities in target cells that possess receptors for that hormone:

• Exerts regulatory influences on the function of other, distant cells reached via the blood or CSF
• Is effective at very low concentrations (i.e. as little as 10-12 M)

Question 2

Target cell

Answer 2

Cell that possesses receptor(s) for a particular hormone

Question 3

What is the (functional) difference between endocrine and exocrine cells?

Answer 3

Endocrine cells release hormones into the surrounding interstitial fluid. Exocrine cells release their secretions onto epithelial surfaces, usually by way of ducts.

Question 4

What is an endocine gland? What are some examples?

Answer 4

A discrete gland whose primary function is the production and secretion of hormones (e.g. steroids, proteins, amines).

E.g. Thyroid, parathyroid, pineal, adrenal

Secretory cells may also be isolated cells distributed amongst cells of other tissues (e.g. gastrin secretion by stomach; CCK secretion by small intestine)

Question 5

Name an organ that has both endocrine and exocrine functions

Answer 5

pancreas

Question 6

How is hormonal regulation achieved through negative feedback?

Answer 6

Endocrine cell secretion is adjusted based on information received from target cells to maintain appropriate activity in the target cells (set point).

In negative feedback, changes in target cell activity trigger secretory responses that act to counteract the original change.

E.g. if activity in target cells is too high and hormones positively stimulate activity, info about current level is sent to endocrine cells that then reduce secretion levels, which reduces activity. Conversely if activity is too low, secretions are increased, which increases target cell activity.

Negative feedback mechansims can (within limits) maintain internal body environment in a relatively stable state that promotes optimal physiological functioning, despite external fluctuations (homeostasis).

Usually mediated by an interaction with the hypothalamus and/or pituitary gland (involves nervous and endocrine systems for integrated control)

Concerned with concentration of free hormones (for those that bind to transport proteins)

Question 7

What is positive feedback? Example?

Answer 7

In positive feedback, an initial change in the activity of target cells induces events that enhance the change. E.g. action potential generation, blood clotting, ovulation

Question 8

What are the two essential features of endocrine control?

Answer 8

1. Slow action (relative to nervous system)/can have protracted effects
2. Broadcast transmission

Question 9

Why does the endocrine system have slower and more protracted effects than nervious system (two features)?

Answer 9

1. Signals (i.e. hormones) usually travel through the bloodstream to reach target tiessues
2. Hormones continue to act until metabolised/inactivated or excreted

Question 10

What does ‘broadcast transmission’ mean in the context of the endocrine control system?

Answer 10

• Hormones released into the bloodstream and cerebrospinal fluid potentially bathe all cells
• Specificity of effects depends upon receptors on target cells

Question 11

Hormones are present in [high/low] concentrations so cellular receptors are generally [high/low] affinity

Answer 11

Hormones are present in low concentrations (10-7 to 10-12 M)
so cellular receptors are generally high affinity

Question 12

What are some processes that are under endocrine control ?

Answer 12

• Water & electrolyte balance
• Metabolism & post-absorptive nutrient homeostasis
• Coping with hostile environments (i.e. stress!)
• Reproduction
• Growth & development

Question 13

What is a local hormone?

Answer 13

Local hormones diffuse through the interstitial fluid to act on target calls in the immediate vicinity of the secretory cell

Question 14

What is a paracrine hormone?

Answer 14

A local hormone that affects neighbouring/neaby cells

Question 15

What is an autocrine hormone?

Answer 15

A local hormone that influences the functions of the same cell that secretes them

Question 16

What is an introcrine?

Answer 16

Introcrines are peptide growth factors or hormones that function within cells in addition to any endocrine, paracrine, or autocrine roles they may have

Question 17

What are the three major calsses of hormones

Answer 17

1. Steroid hormones
2. Peptide and protein hormones
3. Amine hormones

Question 18

What are some of the properties of steroid hormones?

Answer 18

• Synthesised from cholesterol
• Secreted by gonads and adrenal cortex
• Lipid soluble so can pass through cell membranes - bind to intracellular receptors
• Transported across cell membrane in some cells (e.g. estrogens)

Question 19

What are some properties of peptide and protein hormones?

Answer 19

• Structured from chains of amino acids
• Vary enormously in molecular size (tripletides –> 200+ AA)
• Soluble in aqueous solutions
• Distinction peptide vs. protein depends mainly on size- functionally not important! Generally called ‘peptide’ hormones regardless

Question 20

What are some examples of peptide/protein hormones?

Answer 20

• antidiuretic hormone (ADH)
• insulin
• growth hormone
• gonadotropin-releasing hormone (GnRH)

Question 21

What are amine hormones?

Answer 21

• Amine hormones are made from modified amino acids

Question 22

What two amine hormone types are derived from tyrosine?

Answer 22

1. Catecholamines
2. Iodothyronines

Question 23

What are some properties of catecholamines? Properties and examples (3)?

Answer 23

• Synthesised from tyrosine
• Often neurotransmitters but also serve as hormones
• Water soluble so stored in intracellular vesicles
• e.g. dopamine, norepinephrine, epinephrine

Question 24

What are iodothyronines? Properties and examples (2)?

Answer 24

• Thyroid hormones
• Rich in iodine and found only in vertebrates
• Lipid-soluble

Question 25

Name an **amine** hormone synthesised from **tryptophan**

Answer 25

* Melatonin * Serotonin

Question 26

What are some properties of **melatonin** and where is it synthesisted?

Answer 26

* Sythesised from **tryptophan** in the ***corpus pinale*** (pineal gland) * Both water- and lipid-soluble and diffuses out through the cell membrane as soon as produced

Question 27

What are the general features of **peptide/protein hormone synthesis**?

Answer 27

* Synthesised at **ribosomes** * Stored in **vesicles** * Secreted **on demand** * Syntheis of a **preprohormone** with **posttranslational processing** to produce a mature hormone is common to all peptide hormones

Question 28

Describe insulin. Where is it synthesised?

Answer 28

* Insulin is a peptide hormone synthesised by by **β cells** in **pancreatic islets of Langerhans** * Produced after meals in response to rise in glucose and AA concentration in the blood * Active insulin consists of **two polypeptide chains** connected by **two disulfide bridges**

Question 29

Describe the **7 steps** involved in **insulin synthesis** and release.

Answer 29

1. A signal sequence (P segment) directs the molecule into the interior of the **rough ER**. Enzymes there cleave this off to produce **proinsulin** 2. Proinsulin moves through the ER and into the **Golgi apparatus** via shuttle vesicles 3. In the Golgi apparatus, **three disulfide bonds** fold the proinsulin molecule 4. The Golgi apparatus buds off vesicles containing proinsulin and enzymes 5. Enzymes cleave the C segment from proinsulin to form **mature insulin** 6. Insulin is stored in secretory vessels awaiting release 7. **Depolarisation** of the cell membrane triggers release by exocytosis

Question 30

In what way is insulin secretion calcium-dependent?

Answer 30

* Exocytosis of the insulin stored in secretory vessels ide dependent on Ca2+ * When blood glucose increases, cellular ATP concentration and inhibition of ATP-gated K+ channels in β cell membrane increase, causing membrane depolarisation * This causes voltage-gated Ca2+ channels to open and allows an influx of Ca2+ which induces exocytosis of insulin-containing vessicles

Question 31

How is insulin secretion regulated by **GLP-1** and **GIP**? How does this explain why insulin response to glucose is greater when administered orally than intravenously?

Answer 31

* Glucagon-like polypeptide 1 (GPL-1) and gastric inhibatory peptide (GIP) are produced by epithelial cells in the GIT and are released when food enters the small intestine * After release, the hormones travel with blood to the pancreas and stimulate β cells to secrete insulin even before substantial amounts of glucose and AA have been absorbed (anticipatory release) * This explains why for a given amount of glucose the insulin response is greater when administered orally than intravenously

Question 32

How does the **autonomic nervous system** play a role in regulating insulin secretion?

Answer 32

* Increased activity in **parasympathetic** nerve fibres that innervate the Islet of Langerhans stimulate secretion (part of the long-loop parasympathetic reflexes activated during eating and digestion) * On the other hand, **norepinephrine** released from **sympathetic** nerve fibres innervating the pancreas, as well as **epinephrine** from the **adrenal medulla** inhibit insulin secretion

Question 33

How is the production of insulin regulated by **negative feedback**?

Answer 33

* As body cells respond & take up glucose, β cells are no longer stimulated to secrete insulin (negative feedback)

Question 34

How and where are steroid hormones produced generally?

Answer 34

* Formed from cholesterol * some obtained from dietary animal fats * **steroidogenic** endocrine cells and liver cells also produce cholesterol * Formed via stepwise reactions catalysed by enzymes in the mitochondria and smooth ER - different enzymes in different intracellular compartments produce different products (see image) * Produced only in the endocrine cells of the **gonads**, **adrenal cortex**, and **placenta**

Question 35

How and when are steroid hormones secreted?

Answer 35

* **Not** stockpiled in vesicles prior to secretion (solubility!) * made from precursors stored in lipid droplets * Secreted immediately * Diffuse across cell membrane

Question 36

How are **water soluble** hormones usually carried in the blood?

Answer 36

Water soluble protein hormones and catecholamines are generally carried in the blood in simple solution but **may** (e.g. growth hormone and IGF-1) be bound to carrier proteins

Question 37

How are **lipid soluble** hormones generally transported in the blood?

Answer 37

Lipid-soluble hormones (steroid hormones, vitamin D3-metabolites, thyroid hormones) are generally transported bound to carrier proteins (from liver) * Bind reversibly with varying degrees of affinity * May be specific or non-specific * Free and bound forms are in equilibrium in the blood * Only the free form is metabolically active (must diffuse across cell membranes) * Carrier proteins provide a reservoir of steroid hormones in blood plasma and extend half life

Question 38

How is secretion rate estimated?

Answer 38

Metabolic clearance of hormones is relatively constant so plasma levels are a good indicator of secretion rate

Question 39

**Specificity** of hormonal effectes is provided by **\_\_\_\_\_\_\_** on target cells. These also allow effects on multiple tissue types and can be **\_\_\_**cellular or **\_\_\_\_\_**cellular.

Answer 39

**Specificity** of hormonal effectes is provided by **receptors** on target cells. These also allow effects on multiple tissue types and can be **extra**cellular or **intra**cellular.

Question 40

\_\_\_\_\_\_\_\_\_\_ of a target cell depends upopn the number of functional receptors. Receptors can be up- or down-regulated to change this.

Answer 40

**Sensitivity** of a target cell depends upopn the number of functional receptors. Receptors can be up- or down-regulated to change this.

Question 41

**Hydrophylic** (i.e. water-soluble) hormones generally bind [**high/low**] affinity [**intra/extra**]cellular receptors.

Answer 41

**Hydrophylic** (i.e. water-soluble) hormones generally bind **high** affinity **extra**cellular receptors.

Question 42

**Protein hormones** use **\_\_\_\_\_\_\_** messenger systems to modulate the biochemical pathways in cells. Termination of activity usually requires dissociation from receptors and occurs due to **[increased/decreased]** plasma hormone concentration. The hormone-receptor complex can also be internalised by \_\_\_\_\_\_\_\_\_\_.

Answer 42

**Protein hormone**s use **secondary** messenger systems to modulate the biochemical pathways in cells. Termination of activity usually requires dissociation from receptors and occurs due to **decreased** plasma hormone concentration. The hormone-receptor complex can also be internalised by **endocytosis**.

Question 43

**Amplification** of signals is an important characteristic of the endocrine system. What is an example of this?

Answer 43

* Epinephrine released by the adrenal glands in response to stress/threat circulates in the blood until it reaches and bathes liver cells that contain ample stored glycogen * Interacts with g-protein coupled receptor system that uses secondary messengers in a signal transduction pathway that amplifies the signal at five different steps such that very low concentrations of epinephrine can result in a very large increase in glucose concentration due to the breakdown of stored glycogen * Total amplification is about 10 million-fold

Question 44

Lipid soluble hormones (e.g. **s\_\_\_\_\_\_\_\_** and **i\_\_\_\_\_\_\_\_**) bind to [**extra/intra**]cellular receptors and often alter **\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_.**

Answer 44

Lipid soluble hormones (e.g. **steroids** and **iodothyronines**) bind to **intra**cellular receptors and often alter **gene expression****.** Some can also bind extracellular receptors and function similarly to water-soluble hormones.

Question 45

How are **steroid** hormones metabolised?

Answer 45

* Conjugation with **sulfuric acid** and **glucuronic acid** to make **glucuronides** and **sulfate**s that are water soluble and re-enter the blood to be excreted by the kidneys

Question 46

As rate of elimination is relatively constant, blood hormone **concentration** depends primarily on ______ \_\_ \_\_\_\_\_\_\_\_\_\_.

Answer 46

As rate of elimination is relatively constant, blood hormone **concentration** depends primarily on **rate of addition**.

Question 47

What is the **half life in plasma** of a hormone?

Answer 47

Time it takes to reduce the concentration of the hormone in blood to be halved after it is injected into the blood. Water-soluble hormones = seconds to minutes. Lipid-soluble hormones = hours to days.

Question 48

What is **peripheral activation** of a hormone? Example?

Answer 48

Conversion to a more active form after secretion by a process. E.g. **thyroid hormone** is secreted mainly as a four-iodine compound also known as tetraiodothyronine, or T4. After T4 is secreted, target and other tissues enzymatically remove one iodine to form triiodothyronine, or T3, which is more physiologically active than T4. E.g. Testosterone to the more active dihydrotestosterone.

Question 49

How do **circadian rhythms** influence endocrine secretion?

Answer 49

* Endogenous diurnal rhythms that can be tuned e.g. by environmental light exposure * Endocrine secretion tied to these occurs outside of feedback contol system e.g. **melatonin** secretion by the pineal gland * Can also be shorter rhythms around 1 hour = **ultradian rhythms**