Introduction to the Endocrine System: Hormones and Receptors Flashcards
What is the endocrine system?
Consists of DUCTLESS endocrine glands, occurring at numerous locations in the body, that secrete hormones into the bloodstream
What are exocrine glands?
E.g: sweat glands - the duct emerges at another body site
Examples of a relationship between the anterior pituitary and adrenal cortex?
Anterior pituitary released adrenocorticotrophic hormones (ACTH), which causes the adrenal cortex to synthesis and release cortisol
3 ways in which specificity of signalling is achieved?
- Chemically distinct hormones
- Specific receptors for each hormone
- Distinct distribution of receptors across target cells, providing an address at which the hormone acts
What are the 7 classic endocrine organs?
Pituitary gland Thyroid gland Parathyroid glands Adrenal glands Pancreas Ovary (female) Testis (male)
Other areas of the body that have an endocrine function?
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)
4 types of hormones?
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
Which hormone types have the shortest and longest duration of action, in general?
Shortest - modified amino acids
Longest - steroid hormones
Main hormones produced by the anterior pituitary and their main targets and function?
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)
Main hormones produced by the intermediate pituitary and their main targets and function?
Melanotrophin-stimulating hormone (MSH) - melanocytes (homeostasis)
Main hormones produced by the posterior pituitary and their main targets and function?
ADH - kidney (homeostasis)
Oxytocin - mammary glands and uterus (reproduction)
Main hormones produced by the pineal and their main targets and function?
Melatonin - hypothalamus (homeostasis)
Main hormones produced by the thyroid and their main targets and function?
Thyroxine (T4) - most tissues (growth and metabolism)
Triiodothyronine (T3) - most tissues (growth and metabolism)
Main hormones produced by the parathyroid and their main targets and function?
Calcitonin - bone, gut (homeostasis)
Parathyroid hormone - bone, gut (homeostasis)
Main hormones produced by the pancreas and their main targets and function?
Insulin - liver, muscle, adipose tissue (growth, metabolism, homeostasis)
Glucagon - liver, muscle, adipose tissue (growth, metabolism, homeostasis)
Main hormones produced by the adrenal cortex and their main targets and function?
Glucocorticoids (inc. corticsol) - multiple sites (growth, metabolism)
Mineralocorticoids (aldosterone) - kidney (homeostasis)
Main hormones produced by the adrenal medulla and their main targets and function?
Adrenaline - multiple sites (growth, metabolism)
Noradrenaline - multiple sites (homeostasis, metabolism)
Main hormones produced by the male gonads and their main targets and function?
Testosterone - testes (reproduction)
Main hormones produced by the female gonads and their main targets and function?
Oestradiol - ovaries and uterus (reproduction)
Progesterone - ovaries and uterus (reproduction)
Main hormones produced by the placenta (in pregnancy) and their main targets and function?
Human chorionic gonadotrophin (hCG) - uterus (reproduction)
Oestradiol - ovaries and uterus (reproduction)
Progesterone - ovaries and uterus (reproduction)
Describe paraneoplasmic syndromes
Some neoplasms that are not “endocrine” produce hormone that cause these, e.g: in Zollinger-Ellison syndrome
Types of chemical signalling?
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
How does amplification of the cell signal from the hormone occur?
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
How is action of a hormone terminated?
Enzyme-mediated metabolic inactivation in the liver, or at sites of action
Describe the complementary action of hormones and give examples
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
Describe antagonistic actions of hormones and give examples
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
Which hormone does antagonise glucose uptake into muscle and adipose tissue?
Adrenaline
How are amine hormones synthesised, stored, released and transporter?
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
How are peptide and protein hormones synthesised, stored, released and transporter?
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
How are steroid hormones synthesised, stored, released and transporter?
Synthesised and secreted UPON DEMAND; the stimuli increase:
- Cellular uptake and availability of cholesterol
- 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
Which form of steroid hormone is biologically active?
Only the “free” form, that is unbound to carrier protein, is biologically active
Which hormones are relatively insoluble in plasma?
Steroids, thyroxine (T4), triiodothyronine (T3)
Functions of carrier proteins?
- Increase amount transported in blood
- Provide a reservoir of hormone
- Extend half-life of the hormone in the circulation (contributing to the long duration of action of, e.g: steroid hormones)
3 important specific carrier proteins?
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
2 important general carrier proteins?
Albumin - binds many steroids and thyroxine
Transthyretin - binds thyroxine and some steroids
Transport of peptides and proteins?
Soluble in plasma and do not require proteins for transport; they typically have a relatively short duration of action because of this
Describe the equilibrium in which carrier proteins are involved
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
Factors that influence plasma conc. of hormones?
Rate of secretion is the primary determinant
Rate of excretion also contributes
Controls on secretion of hormones?
- Negative feedback - maintains plasma conc. at a set level
- Neuroendocrine - elicits a sudden burst in secretion to meet a specific stimulus
- 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)
An example of a negative feedback system?
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
What does trophic mean?
A hormone that acts upon another endocrine gland to regulate its secretion of hormone
Route by which hormone elimination occurs?
There are several but, generally, metabolism by the liver and excretion by the kidney are most important
[Hormone]p = secretion - elimination
Half-lives of different types of hormones?
Amines e.g. adrenaline - t½ ~ seconds
Proteins and peptides - t½ ~ minutes
Steroids and thyroid hormones - t½ ~ hours-days, due to extensive protein binding
3 types of hormone receptors?
- GPCRs - activated by amines and some proteins/peptides; major signalling pathways inv. coupling to Gs, Gi, or Gq
- Receptor kinases - activated by some proteins/peptides
- Nuclear receptors - can be subdivided into class 1 and 2 and a hybrid class
Different classes of nuclear receptors?
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
Which of the hormone receptors are cell-surface receptors and which are the intracellular receptors:
Cell-surface receptors:
• GPCRs
• Receptor kinases
Intracellular receptors (ligand is lipophilic, allowing diffusion across the plasma membrane): • Nuclear receptors
Mechanism of signalling via GPCRs (cAMP pathway?
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
Mechanism of signalling via GPCRs (IP3, PKC pathway)?
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
Examples of a hormone that signals via receptor kinases?
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
What are nuclear receptors?
Ligand-gated transcription factors
Mechanism of signalling via nuclear receptors (class 1)?
- Steroid hormones are lipophilic molecules that enter cells via diffusion across the plasma membrane
- 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
- Receptor-steroid complex moves to the nucleus, forms a dimer and binds to hormone response elements in DNA
- 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
