Endocrinology intro (1) Flashcards
Cell communication: comparison of hormone vs nervous system control
Nervous communication: fast, rapidly modulated message:
cells communicate electrically by precise, defined fibres, NTs, & effector cells
Hormones: provides a slower developing, widespread regulatory action:
(endocrine, paracrine, autocrine, neuroendocrine, neurotransmitters, exocrine)
Types of hormone secretion
(see diagram in notes)
- endocrine: from cell to blood stream and can bind to relevant receptors anywhere in the body
-neuroendocrine nerve cell to blood stream
-paracrine: secretion has local effect e.g. secretion into digestive tract
-neurotransmitters: transmit messages between neurons and between neurons to muscles
- autocrine: effect on the cell that produces
(We’ll be focusing on endocrine in these lectures)
Endocrine system
Made up of ductless glands scattered through the body that secrete hormones which travel in blood to target cells
–Targets cells have specific receptors for hormone
–Regulate or direct particular function
Two hormone groups (classified according to their solubility)
Hydrophilic:
*Peptide hormones
*catecholamines
Lipophilic:
*Steroid hormones
*Thyroid hormones
Hormones
Endocrine cell secretes hormones ->
plasma hormone is:
excreted
THEN
inactivated by metabolism
OR
activated by metabolism/ catalyses hormone formation
resulting in actions on target cells
*Plasma levels of hormones are controlled by change in rate of secretion
*Direct regulatory inputs influence secretory output:
-Neural input
-Other hormone
*Effective plasma levels also affected by:
-Activation
-Metabolism/clearance
Major endocrine glands
See diagram
- hypothalamus
-pituitary gland
-thyroid gland
-adrenal glands
- pancreas
- ovaries/testes
Hormone receptor interaction
Hormones have specificity
Many drugs block receptors (antagonistic) or are agonists and enhance receptor response
*lock and key hypothesis
*complimentary chemical configuration
*confers control / specificity
*drug actions
Hydrophillic hormones have extracellular receptors
hydrophilic hormones cannot pass through the lipid membrane so they require extracellular receptors to convey the message to the inside of the cell.
see diagram in notes: Pictures 1-3 show hydrophillic hormone and picture 4 shows lipophillic hormone action:
1 – by activating an ion channel
2- by direct control of effector enzyme
3- by indirect (G-protein) coupling via second messengers/ ion channels
4- lipophilic hormones can go straight through the membrane to bind to a receptor in the nucleus or elsewhere in the cell
** much more goes on in the cell these diagrams are simplified**
Signal transduction
Signal -> receptor activation
Transduction is the process where stimulus is turned into response
Transduction pathways available:
a) by activating an ion channel
b) by direct control of effector enzyme
c) by indirect (G-protein) coupling via second messengers/ ion channels
Steroid hormones
Steroid hormones (lipophilic) have intracellular receptors:
*Hormones circulate bound to carrier proteins
*Free hormone can pass through membrane to receptor
-Activation occurs
-Dimer binds to specific regions of DNA changes in gene expression: mRNA produced
-Relevant protein synthesised: response
-Lipophilic hormones can move through the plasma membrane but are relatively insoluble in plasma fluid so they often require carrier proteins to move around
- medically, free and bound percentages of the hormone are important – a lack of binding carriers can lead to hormone overload and disease
Synthesis of peptide hormones
- synthesised as a large pre- hormone and small parts split off into pro-hormone
- pro-hormones tend to be packaged and small sections are divided off as hormones
- hormones are stored in vesicles and secreted when triggered
In type 2 diabetes there is no stored insulin so first phase is lost
Comparison of steroid and peptide hormones
Steroids aren’t stored and are made on demand
Peptides can’t enter the cell (need an extracellular receptor) and are rapidly broken down – short half-life (minutes), impact minutes to hours
– peptides are stored and released as required
Steroids are broken down more slowly, as they are lipid soluble receptors are within the cell – long half-life (hours), impact hours to days
-Steroids aren’t stored and are made on demand
property/ peptide/steroid (see notes for table)
Synthesis
p- Stored as inactive precursor
s- Usually not stored made on demand
Cell membrane permeability
p-Water soluble unable to cross
s- Lipid soluble pass easily- diffusion
Receptors
p -Membrane bound extracellular
s- Intracellular
Transport
p- In solution in blood
s- Poorly soluble- bound to plasma proteins
Metabolism
p- Rapidly broken down
s- Slowly degraded
Half-life
p- Short (mins)
s- Long (hours)
Duration of effects
p- Mins-hours
s- Hours-days
Hormones and homeostasis
*Hormones contribute to homeostasis
*To maintain homeostasis control systems need to:
-Detect changes
-Integrate information from sources
-Make adjustments to restore the “normal” situation
*Two groups of control system:
-Intrinsic – local control – within organ
-extrinsic – further away – external to organs impacting multiple organs
Control systems
*Feedforward:
Action taken in anticipation of a change
e.g. salivation (Pavlov’s dog) and digestive stimulation in advance of food
(from thinking about it etc.)
*Feedback:
Response made after detecting a change in the system
Two types: negative and positive
e.g. pos - in pregnancy oxytocin encourages more oxytocin release
Control of hormone secretion
Most hormones are released episodically (in short bursts) eg. circadian rhythm (24hr cycle)
For example: cortisol level rises approx. 2 hours before you usually get up in a 24 hour cycle
Circannual rhythms also exist (year cycle) e.g. flower blooming, breeding cycles in most animals
For example: Sparrow testicles get larger may – august breeding season
Other hormones are produced on demand rather than according to a rhythm
Mechanisms of control:
-control by other hormones
-control by neurons
-control by plasma levels of nutrient or mineral eg insulin in response to glucose levels
(^ also influenced by rate of activation or metabolic inactivation, excretion, binding to plasma proteins)
Feedback in control of hormonal systems
negative feedback:
Acts to damp hormonal response ie extremes of hormone concentration are limited
alters the plasma concentration of a hormone in a direction opposite to that of previous change
Positive feedback:
Initial change in system starts a sequence of events that leads to further disturbance
Hypothalamus and pituitary gland anatomy:
Hypothalamus is a down-growth of the brain full of neurones the pituitary descends below this
Connection between hypothalamus and pituitary
*Axons from 2 groups of hypothalamic neurons pass down the infundibulum and end in posterior pituitary
*no important neural connections between hypothalamus & anterior pituitary but these areas are connected by blood vessels
*Capillaries at base of hypothalamus, the medidan eminence, recombine to form the hypothalamo-pituitary portal vessels.
*The short portal vessels connect anterior with posterior pituitary
Releasing hormones aka releasing factors
Secretion of each anterior pituitary hormone is stimulated or inhibited by one or more hypothalamic hypophysiotropic hormones (more detail in next lecture)
Hormone/ Effect on Anterior Pituitary
Thyrotropin-Releasing hormone (TRH)
Stimulates release of TSH
Corticotropin-Releasing hormone (CRH)
Stimulates release of ACTH
Gonadotropin-releasing hormone (GnRH)
Stimulates release of FSH and LH
Growth-hormone releasing hormone (GHRH)
Stimulates release of growth hormone
Growth-hormone inhibiting hormone (SS) somatostatin
Inhibits release of growth hormone and TSH
Prolactin-releasing factors (PRF)
Stimulate release of prolactin
Dopamine (prolactin inhibiting hormone)
Inhibits release of prolactin
Control of hormone secretion from anterior pituitary by hypothalamic releasing hormones
*Releasing hormones are synthesised in neurons of hypothalamus
*Neurons terminate in median eminence around capillaries that are origins of hypothalamo-pituitary portal vessels
*Action potentials cause release of hormones into portal vessels which are carried to anterior pituitary
(see diagram)
Other control of the HP axis
*Neural
Hypothalamus receives inhibitory & excitatory input from CNS.
Stimuli include: pain, sleep, emotion, fright, light etc
*Other hormones
Other hormones can influence secretion in a positive or negative way:
-Permissiveness – one hormone allows another hormone to act
-Synergism – additive effect
-Antagonism – inhibitory effect
Major types of endocrine disorder
*Hypersecretion: can be primary or secondary
*Hyposecretion: can be primary or secondary
*Hyperresponsiveness of target cells due to an upregulation in receptors or increase in number
*Hyporesponsiveness ie decreased response of target cells, due to down- regulation or low distribution of receptors
What affects action of hormones?
-Quantity of hormone and quantity of receptors
-Testosterone in its active form causes hair growth according to receptor distribution and number – hence why some men have hairy chests
Endocrine disorder example: Cushings syndrome/ Cushings disease
CRH (hypothalamus) -> ACTH (anterior pituitary) -> Cortisol (adrenal)
primary production of excess cortisol by the adrenals or secondary hypersecretion of ACTH resulting in increased cortisol
Cushings syndrome = anything causing elevated cortisol
Cushings disease = high levels of cortisol due to hypersecretion of CTH due to pituitary tumour
Type 2 diabetes usually due to insulin resistance – insulin is produced but not responded to = hyporesponsiveness (linked to inflammation)
Posterior pituitary hormones:
Hormones of the neurohypophysis: Representation of structural relationships in posterior pituitary
*The posterior lobe of the pituitary develops as a downgrowth from the hypothalamus and remains joined to this by the hypothalamo-hypophysial nerve tract.
*Hormones synthesised within cell bodies of large neurons lying in supraoptic and paraventricular nuclei of the hypothalamus
^Hormones are synthesised in the bodies of large neurones located in thehypothalamus and released from the dendritic ends of these neurones - located in the posterior pituitary and therefore commonly referred to as posterior pituitary hormones.
Posterior pituitary hormones
*Oxytocin
*Vasopressin aka ADH or AVP affects blood vessel dilation
^ They are both nonapeptides with disulphide bridge linking amino acids 1 and 6 to form a ring
*Hormones are synthesised in the hypothalamus, packaged in granules with a larger protein called neurophysin which acts as a transport protein.
*Granules are transported down the fibres to the terminals of axons located in posterior pituitary.
*When the neurons are stimulated, granules released & contents diffuse into adjacent capillaries.
*Prior to secretion, hormones are stored in secretory granules in terminals themselves or Hering bodies along the length of the axons.
*Both oxytocin and vasopressin are secreted by calcium-dependent exocytosis similar to the secretion of NTs at other nerve terminals.
*Once released they circulate in the blood as free hormones. (1/2 life: few minutes)
*Kidneys, liver & brain are main sites of clearance.
*Both act on their target glands by G protein-linked cell surface receptors
