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Summary hormones, brain and behavior (PSY3370/IPN3370)
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Task 1: HormonesWhat are hormones? What are the functions of hormones? What is the difference between hormones and
neurotransmitters?
What is endocrinology?
Endocrinology is the study of hormones and their actions.
Hormones are chemical messengers, released into the blood, that act through receptors to cause a change in
the target cell.
Hormon = exciting or setting in motion
The glands that release hormones are ductless, giving the term endocrine for internal secretion > synthesize and
releases hormones into the bloodstream.
o Major endocrine glands: hypothalamus, anterior pituitary, posterior pituitary,
thyroid, parathyroid, adrenal cortex, adrenal medulla, pancreas, stomach and
gut, ovaries, testes and kidneys.
o Pancreas has endocrine but also exocrine functions.
Vascular endothelium, the gastrointestinal tract and the skin should also be
considered to be endocrine organs as they all release hormones or their
precursors into the blood.
o Form the diffuse endocrine system (located throughout the whole body):
consists of scattered endocrine cells,
located in various different tissues, that
secrete hormones but do not form a
discrete endocrine gland.
Endocrine disorders are very common.
What do hormones do?
Control regulatory systems in the body,
including homeostasis, metabolism and
reproduction.
Making sure that blood levels of sodium,
potassium, calcium and glucose stay within set
limits.
Negative feedback systems.
Hormones vs neurotransmitter
There are two major regulatory systems in the body: the neural system and the endocrine system. Both use chemical
messengers but set up differently and different functions.
Neural regulation: the neurotransmitter is released, in
response to an action potential, from a nerve ending into
the synaptic cleft, directly onto the surface of the target
cell.
o Very rapid & delivers its messenger directly to the
surface of its target cell.
Endocrine regulation: the hormone is released from the
cells of an endocrine or ‘ductless’ gland into the
bloodstream where the hormones travel to target cells
often at some distance.
o Control is generally slower, acts over a longer period
of time and are more long lasting & puts its
Testosterone
messengers into the blood and allows for diffusion
from the blood to the target cell.
Neuroendocrine regulation: the hormone is secreted by a
nerve cell in response to an action potential, but is
released into the bloodstream, not a synaptic cleft, and
then acts as a hormone
o Oxytocin, dopamine, adrenaline
Hormone antagonism and synergy Pineal gland > melatonine
, Agonist: when it has an effect.
Antagonist of the first hormone: opposite effect.
Body used more than one hormone to achieve control > very often acts in opposition > one or more will tend to
increase the level of the substance, while one or more will act to decrease it.
o Allows considerable fine control and responsiveness to a changing environment.
o Can afford protection against a potentially devastating change in the level of the substance.
Synergy: hormones which exert the same effect have much greater action when the two act together than either
of them can have individually.
Endocrine axis
Many hormones function as part of a cascade, so that the target tissue of one hormone is another endocrine gland.
Thyrotropin releasing hormone (TRH) from the hypothalamus > stimulates the release of pituitary TSH >
stimulates release of thyroxine from the thyroid.
The cascade allows amplifications of signal, flexibility of response to a variety of physiological stimuli and fine
regulation of levels of the end hormonal product.
= endocrine axis.
What classes of hormones are there? What are the mechanisms involved in hormone production and
secretion?
Divided by chemical structure > implications for the way in which these hormones are stored, released, transported
in blood, their mechanism of action and route of administration.
Peptide hormones: made of chains of amino acids.
= hydrophilic (water-soluble), dissolve readily in plasma, but cannot enter the
target cell, so interact with receptors on the cell surface.
Must be injected, to avoid being inactivated by digestive enzymes.
Most numerous type of hormone.
Structure: Peptide hormone-secreting cells are distinguished by the large
amounts of rough endoplasmic reticulum, prominent Golgi apparatus and by
the presence of secretory granules, containing the finished hormone ready for
secretion.
Posttranslational processing in the Golgi apparatus and secretory granules >
modification of the basis peptide sequence before being secreted.
Storage: Are preformed, and stored in granules within the endocrine cell, ready
for release in response to a signal.
Release: Need a specific secretory mechanism > exocytosis.
Transport: does not need binding protein.
Metabolism: mainly following binding to a receptor in the target cell. The
hormone–receptor complex is internalized, and the hormone undergoes
degradation in a lysosome. Most peptide hormones have a short half-life of just
a few minutes, although the larger glycosylated peptide hormones such as
thyroid stimulating hormone and luteinizing hormone have a longer half-life.
Examples: TRH, TSH, melatonine
Steroids: all made from cortisol and have common core structure.
= lipophilic, dissolve poorly in plasma and are mostly transported in blood bound to carrier proteins, but readily
enter cells to interact with cytoplasmic of nucleur receptors.
Orally active
Same for thyroid hormones.
Structure: Presence of unusually large amounts of smooth endoplasmic reticulum and mitochondria & significant
lipid droplets, containing cholesterol esters, as steroid-secreting cells store the precursor.
Storage: store the precursor to hormone synthesis rather than the finished product > cholesterol, the substrate for
steroid biosynthesis (by enzymes within the steroid-secreting cell, located either within the mitochondria or the
smooth endoplasmic reticulum) > steroid hormones being lipid soluble, are difficult to store, whereas cholesterol
can be esterified and stored easily.
Release: do not require a specific secretory mechanism: they simply diffuse across the plasma membrane and out
, of the cell down a concentration gradient.
Transport: need to be transported in blood bound to a carrier or binding protein. But, not all steroids have a
bounding protein (aldosterone).
Metabolism: Steroids may be excreted by the kidney in unchanged form but mostly, they undergo metabolism in
the liver into more water-soluble forms which are then excreted in bile and in the urine.
Examples: cortisol, testosterone, progesterone.
Derivatives from amino acids: Based on single amino acid. Catecholamines: dopamine, adrenaline and
noradrenaline:
= hydrophilic (water-soluble), dissolve readily in plasma, but cannot enter the target cell, so interact with receptors
on the cell surface.
Storage: Synthesized then stored in granules in the cells to be released as soon as they are needed.
Transport: does not need binding protein.
Metabolism: catechol-O-methyltransferase (COMT) which is found in most tissues but especially blood vessels,
and by monoamine oxidase (MAO) in neural tissues.
Binding protein has three functions:
Increase solubility of the hormone in the blood.
Create a readily accessible reserve of the hormone in the blood. Only the fraction that is not bound is biologically
active (available to exert its physiological effects but is also susceptible to metabolism or excretion).
o Measuring circulating concentrations of hormones: total hormone or only the biologically active hormone?
Increase the biological half-life of the hormone. The biological half-life of a hormone is the time taken for half
the hormone present in blood to be metabolized or excreted.
o Binding proteins increase the biological half-life of a hormone by protecting it from metabolism and
excretion.
Metabolism
Metabolism does not only result in their inactivation > some principal secreted
hormone being inactive and requiring metabolism to produce the active version
(testosterone).
Endocrine release: hormone travels from cells where they are made, in the
bloodstream, to reach the cells where they act. From a ductless gland into the
blood.
Exocrine release: secrete substances into a duct > usually affect distant organs
>less common > gastric gland into stomach
Paracrine (signaling): hormones act locally on different cell types in the tissue
where they are produced.
Autocrine (signaling): act directly on the same type of cell that secretes them.
Hormones may have a mixture of different types of action.
Patterns of hormone secretion
Episodic secretion: involved the maintenance of a set point by correcting of any deviation from this point.
Homeostatic mechanism
Example, plasma calcium concentrations > deviation from set points triggers episodic secretion.
Some are always secreted episodically or in bursts.
Diurnal variation: predictable daily pattern
, Growth hormone: low during the day but increase during early part
of sleep.
The main regulator of the 24-h periodicity of hormone secretion is
the ‘body clock’, principally the suprachiasmatic nucleus (SCN) in
the hypothalamus.
However, other factors can influence the diurnal pattern of
secretion.
Set point regulation
Unusual
Thyroxine: only changes over weeks or months (long half-life).
Most have diurnal with episodic secretion.
Feedback systems
Negative feedback
The simplest form is where the final product of an endocrine cascade acts to inhibit
release of hormones higher up the cascade > thyroxine acts on both the hypothalamus
and anterior pituitary to decrease the production of TRH and TSH.
Does not mean that hormone production is switched on and off like a light switch. All
endocrine systems are dynamic, in other words they are responsive to change and with a
tendency to return to the basal or residual state of activity.
Delayed feedback: most negative feedback operates through a genomic mechanism
resulting in a decrease in the production of hormones higher up the endocrine axis > takes
hours to days.
o Determined by the amplitude and duration of the end-product response.
Fast feedback: without genomic mechanism and can take place within 10 minutes (HPA-
axis).
o Triggered by the gradient of the increase and kicks in when hormone levels rise
rapidly.
Some systems also have short feedback loops which allow intermediate products of an endocrine axis to exert
negative feedback at higher levels. This suggests that there are specific mechanisms to allow transport of certain
peptide hormones across the blood–brain barrier.
So, in summary, the CRH–ACTH–cortisol cascade is regulated by both classical negative feedback
from cortisol (the end-product) and by short-loop feedback from ACTH (the intermediate
product).
What is the HPA-axis?
The hypothalamo–pituitary–adrenal axis
Hypothalamus secretes corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) >
acts on the corticotroph cells of the anterior pituitary which releases adrenocorticotropic
hormone (ACTH) > signal the adrenal cortex which releases cortisol into the bloodstream.
Cortisol has negative feedback effects both at the level of the hypothalamus, inhibiting CRH and
AVP secretion, and the pituitary, inhibiting ACTH secretion.
hypothalamo–pituitary–adrenal (HPA) axis.
Cortisol is produced by cells of the zona fasciculata and reticularis.
The actions of CRH and AVP together is greater than the sum of their individual effects. They
activate different intracellular pathways and act through G-protein coupled receptors on the
corticotroph cells.
o CRH receptors are linked to cAMP generation.
o AVP receptors are linked to intracellular calcium signaling.
Diurnal variation in ACTH production and secretion, and therefore in serum
cortisol concentrations, with a peak at 6 to 9 h. Serum cortisol is therefore
usually sampled at 9h.
HPA axis also stimulated by stress, both by physiological stressors, such as cold
exposure, infection, hypoglycaemia and exercise, and also by psychological
stressors.
Hippocampus, amygdala and PFC can influence this axis > activate or stop by evaluation.
SCN communicates with other neurons in the hypothalamus to start the activation of the HPA axis.
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