Introduction to the Endocrine System: Hormones and Receptors

Question 1

What is the endocrine system?

Answer 1

Consists of DUCTLESS endocrine glands, occurring at numerous locations in the body, that secrete hormones into the bloodstream

Question 2

What are exocrine glands?

Answer 2

E.g: sweat glands - the duct emerges at another body site

Question 3

Examples of a relationship between the anterior pituitary and adrenal cortex?

Answer 3

Anterior pituitary released adrenocorticotrophic hormones (ACTH), which causes the adrenal cortex to synthesis and release cortisol

Question 4

3 ways in which specificity of signalling is achieved?

Answer 4

1. Chemically distinct hormones
2. Specific receptors for each hormone
3. Distinct distribution of receptors across target cells, providing an address at which the hormone acts

Question 5

What are the 7 classic endocrine organs?

Answer 5

Pituitary gland
Thyroid gland
Parathyroid glands 
Adrenal glands
Pancreas
Ovary (female)
Testis (male)

Question 6

Other areas of the body that have an endocrine function?

Answer 6

There are other endocrine organs, e.g: pineal gland, hypothalamus, thymus

There are also organs that have an endocrine function, amongst others:
• Heart (ANP)
• GI tract
• Kidneys (erythropoietin)

Question 7

4 types of hormones?

Answer 7

Modified amino acids, e.g: from tyrosine, tyramine - these inc. adrenaline, thyroid hormones (T3, T4)

Steroid hormones (derived from cholesterol) - these inc. cortisol, progesterone, testosterone

Peptides (from large precursor proteins/polypeptides) - these inc. ACTH, ADH, oxytocin

Proteins - these inc. insulin

Question 8

Which hormone types have the shortest and longest duration of action, in general?

Answer 8

Shortest - modified amino acids

Longest - steroid hormones

Question 9

Main hormones produced by the anterior pituitary and their main targets and function?

Answer 9

ACTH - adrenal cortex (metabolism)

GH - liver, bones and muscle (growth)

FSH - gonads (reproduction)

LH - gonads (reproduction)

Prolactin - mammary glands (reproduction)

Thyroid-stimulating hormone (TSH) - thyroid (growth, metabolism)

Question 10

Main hormones produced by the intermediate pituitary and their main targets and function?

Answer 10

Melanotrophin-stimulating hormone (MSH) - melanocytes (homeostasis)

Question 11

Main hormones produced by the posterior pituitary and their main targets and function?

Answer 11

ADH - kidney (homeostasis)

Oxytocin - mammary glands and uterus (reproduction)

Question 12

Main hormones produced by the pineal and their main targets and function?

Answer 12

Melatonin - hypothalamus (homeostasis)

Question 13

Main hormones produced by the thyroid and their main targets and function?

Answer 13

Thyroxine (T4) - most tissues (growth and metabolism)

Triiodothyronine (T3) - most tissues (growth and metabolism)

Question 14

Main hormones produced by the parathyroid and their main targets and function?

Answer 14

Calcitonin - bone, gut (homeostasis)

Parathyroid hormone - bone, gut (homeostasis)

Question 15

Main hormones produced by the pancreas and their main targets and function?

Answer 15

Insulin - liver, muscle, adipose tissue (growth, metabolism, homeostasis)

Glucagon - liver, muscle, adipose tissue (growth, metabolism, homeostasis)

Question 16

Main hormones produced by the adrenal cortex and their main targets and function?

Answer 16

Glucocorticoids (inc. corticsol) - multiple sites (growth, metabolism)

Mineralocorticoids (aldosterone) - kidney (homeostasis)

Question 17

Main hormones produced by the adrenal medulla and their main targets and function?

Answer 17

Adrenaline - multiple sites (growth, metabolism)

Noradrenaline - multiple sites (homeostasis, metabolism)

Question 18

Main hormones produced by the male gonads and their main targets and function?

Answer 18

Testosterone - testes (reproduction)

Question 19

Main hormones produced by the female gonads and their main targets and function?

Answer 19

Oestradiol - ovaries and uterus (reproduction)

Progesterone - ovaries and uterus (reproduction)

Question 20

Main hormones produced by the placenta (in pregnancy) and their main targets and function?

Answer 20

Human chorionic gonadotrophin (hCG) - uterus (reproduction)

Oestradiol - ovaries and uterus (reproduction)

Progesterone - ovaries and uterus (reproduction)

Question 21

Describe paraneoplasmic syndromes

Answer 21

Some neoplasms that are not “endocrine” produce hormone that cause these, e.g: in Zollinger-Ellison syndrome

Question 22

Types of chemical signalling?

Answer 22

Autocrine - act on the the same cell that produced it

Paracrine - acting on the cells in the vicinity around the one from which it was produced

Endrocrine - signalling molecule enters circulation

These are not absolute distinctions; a hormone can signal in one way in one tissue but signal in another way in another tissue, e.g: somatostatin acts in a paracrine manner in the pancreas and in an endocrine manner in the brain

Question 23

How does amplification of the cell signal from the hormone occur?

Answer 23

Activated receptor engages a signal transduction that differs between individual receptors but causes amplification of the original signal, i.e: the receptor can activate several G-proteins, with each one of these activating several effector molecules

Question 24

How is action of a hormone terminated?

Answer 24

Enzyme-mediated metabolic inactivation in the liver, or at sites of action

Question 25

Describe the complementary action of hormones and give examples

Answer 25

Of several hormones, can regulate many complex physiological function on short and long-term scales, e.g: • Adrenaline, cortisol and glucagon all contribute to bodily response to short-term intense exercise, enhancing physical performance and preventing potential hypoglycaemia and hypokalaemia • GH, insulin, IGF-1 and sex steroids are essential, long-term, for growth

Question 26

Describe antagonistic actions of hormones and give examples

Answer 26

Can occur via the balance of opposing influences, e.g: • Insulin - lower plasma glucose levels by INHIBITING hepatic gycogenolysis and gluconeogenesis and by STIMULATING glucose uptake into muscle and adipose tissue • Glucagon - increases plasma glucose levels by STIMULATING hepatic glycogenolysis and gluconeogenesis but does NOT antagonise glucose uptake into muscle and adipose tissue

Question 27

Which hormone does antagonise glucose uptake into muscle and adipose tissue?

Answer 27

Adrenaline

Question 28

How are amine hormones synthesised, stored, released and transporter?

Answer 28

Pre-synthesised from amino acids, e.g: tyrosine is converted into adrenaline They are stored in vesicles and released in response to receptor stimulation, by a ligand, and then Ca2+-dependent exocytosis Amines are HYDROPHILIC and are transported mainly "free" in plasma

Question 29

How are peptide and protein hormones synthesised, stored, released and transporter?

Answer 29

Pre-synthesised, usually from a longer precursor: • Precursor protein is synthesised at RER • Converted into the mature hormone with CONVERTASES They are stored in vesicles and released in response to stimuli by Ca2+-dependent exocytosis Peptides are HYDROPHILIC and are transported mainly "free" in plasma

Question 30

How are steroid hormones synthesised, stored, released and transporter?

Answer 30

Synthesised and secreted UPON DEMAND; the stimuli increase: 1. Cellular uptake and availability of cholesterol 2. Rate of conversion of cholesterol to PREGNENOLONE (rate-limiting step) Cholesterol is uptaken and, e.g: converted to cortisol, via multiple biosynthetic pathway (all via pregnenolone); this is not stored but is immediately secreted Steroids are HYDROPHOBIC (and lipophilic) and are transported in plasma bound to plasma protein, mostly

Question 31

Which form of steroid hormone is biologically active?

Answer 31

Only the "free" form, that is unbound to carrier protein, is biologically active

Question 32

Which hormones are relatively insoluble in plasma?

Answer 32

Steroids, thyroxine (T4), triiodothyronine (T3)

Question 33

Functions of carrier proteins?

Answer 33

1. Increase amount transported in blood 2. Provide a reservoir of hormone 3. Extend half-life of the hormone in the circulation (contributing to the long duration of action of, e.g: steroid hormones)

Question 34

3 important specific carrier proteins?

Answer 34

Cortisol-binding protein (CBG) - binds cortisol in a selective manner and also some aldosterone Thyroxine-binding globulin (TBG) - binds thyroxine (T4) selectively and also some triiodothyronine (T3) Sex steroid-binding globulin (SSBG) - binds mainly testosterone and oestradiol

Question 35

2 important general carrier proteins?

Answer 35

Albumin - binds many steroids and thyroxine Transthyretin - binds thyroxine and some steroids

Question 36

Transport of peptides and proteins?

Answer 36

Soluble in plasma and do not require proteins for transport; they typically have a relatively short duration of action because of this

Question 37

Describe the equilibrium in which carrier proteins are involved

Answer 37

Act as a buffer and reservoir that helps maintain constant conc. of free lipophilic hormone in the blood; FREE and BOUND hormone are in equilibrium: • Only free hormone can cross the capillary wall to active receptors in target tissues • Surges in hormone secretion are buffered by binding to carriers – free concentration does not rise abruptly • This is replaced by bound hormone dissociating from carrier proteins

Question 38

Factors that influence plasma conc. of hormones?

Answer 38

Rate of secretion is the primary determinant Rate of excretion also contributes

Question 39

Controls on secretion of hormones?

Answer 39

1. Negative feedback - maintains plasma conc. at a set level 2. Neuroendocrine - elicits a sudden burst in secretion to meet a specific stimulus 3. Diurnal (Circadian) rhythm - secretion rate fluctuates (up and down) as a function of time, i.e: it is entrained to certain cues, like night and day (e.g: plasma cortisol conc. peaks just before midday and troughs just before midnight)

Question 40

An example of a negative feedback system?

Answer 40

Hypothalamus is influenced by stress and secretes corticotrophin-releasing hormone, which acts on the anterior pituitary and causes release of adrenocoticotrophic hormone This acts on the adrenal cortex (has multiple physiological effects), which secretes cortisol; this then -vely feedbacks to regulate its own secretion

Question 41

What does trophic mean?

Answer 41

A hormone that acts upon another endocrine gland to regulate its secretion of hormone

Question 42

Route by which hormone elimination occurs?

Answer 42

There are several but, generally, metabolism by the liver and excretion by the kidney are most important [Hormone]p = secretion - elimination

Question 43

Half-lives of different types of hormones?

Answer 43

Amines e.g. adrenaline - t½ ~ seconds Proteins and peptides - t½ ~ minutes Steroids and thyroid hormones - t½ ~ hours-days, due to extensive protein binding

Question 44

3 types of hormone receptors?

Answer 44

1. GPCRs - activated by amines and some proteins/peptides; major signalling pathways inv. coupling to Gs, Gi, or Gq 2. Receptor kinases - activated by some proteins/peptides 3. Nuclear receptors - can be subdivided into class 1 and 2 and a hybrid class

Question 45

Different classes of nuclear receptors?

Answer 45

Class 1 - activated by many steroid hormones and move to the nucleus when activated (in the absence of activating ligand, mainly located in the cytoplasm bound to inhibitory heat shock proteins) Class 2 - activated mostly by lipids and are constitutively present in the nucleus Hybrid class - activated by thyroid hormone (T3) and other substances; they are similar in function to class 1

Question 46

Which of the hormone receptors are cell-surface receptors and which are the intracellular receptors:

Answer 46

Cell-surface receptors: • GPCRs • Receptor kinases ``` Intracellular receptors (ligand is lipophilic, allowing diffusion across the plasma membrane): • Nuclear receptors ```

Question 47

Mechanism of signalling via GPCRs (cAMP pathway?

Answer 47

cAMP can act as a secondary messenger Hormones, e.g: adrenaline, corticotrophin-releasing hormone and glucagon, bind to the GPCR; this modulates Gs to +vely modulate adenylyl cyclase, which allows conversion of ATP to cAMP. In turn, cAMP activates protein kinase A that phosphorylates target proteins and has cellular effects Hormones, e.g: melatonin, bind to the GPCR; this modulates Gi, which -vely modulates adenylyl cyclase, preventing the conversion of ATP to cAMP

Question 48

Mechanism of signalling via GPCRs (IP3, PKC pathway)?

Answer 48

Hormones, e.g: angiotensin II, gonadotrophin-releasing hormone and thyrotropin-releasing hormone, modulate Gq to +vely modulate phospholipase C, converting PIP2 to IP3 IP3 binds to its receptor on the ER, allowing Ca2+ efflux which has cellular effects Another pathway is the release of DAG from phospholipase C, which +vely modulates protein kinase C (PKC) to phosphorylate target proteins that have cellular effects

Question 49

Examples of a hormone that signals via receptor kinases?

Answer 49

Insulin receptor: • Binding of insulin causes auto-phosphorylation of intracellular tyrosine residues • Recruitment of multiple adapter proteins, notably IRS1 (these are also tyrosine-phosphorylated) The insulin receptor substrate proteins have cellular effects

Question 50

What are nuclear receptors?

Answer 50

Ligand-gated transcription factors

Question 51

Mechanism of signalling via nuclear receptors (class 1)?

Answer 51

1. Steroid hormones are lipophilic molecules that enter cells via diffusion across the plasma membrane 2. Within the cell, they combine with an intracellular receptor producing dissociation of inhibitory HSP proteins; in the case of the steroid (but not thyroid hormone) receptors, the inactive receptor is located in the cytoplasm 3. Receptor-steroid complex moves to the nucleus, forms a dimer and binds to hormone response elements in DNA 4. Transcription of specific genes is either ‘switched-on’ (transactivated) or ‘switched off’ (transrepressed) to alter mRNA levels and the rate of synthesis of mediator proteins