BMS14 - Endocrine System :thought_balloon: (Histology of the Endocrine…
BMS14 - Endocrine System
Introduction to the Endocrine System
The endocrine system is a major communication system similar to the nervous system. The differences are that the endocrine system is
often intermittent, with a widespread effect which is often long term.
An endocrine system usually functions in this format:
Endocrine cells secrete hormone into the blood or into the intracellular fluid - this depends on the type of hormone in question.
There are different types of hormones. They have different biochemical structures which affects
how the hormone circulates, it's half life and also it's mechanism of action
These hormones are usually synthesised as preprohormones, then cleaved using enzymes into prehormones which are then stored in storage vesicles. The active hormone is then released via exocytosis due to an increase in Ca2+ conc.
Protein hormones are water soluble and so travel unbound- they tend to be cleared rapidly by the liver and so have a short half life. This means they are under tighter control.
A majority of hormones are
. These vary from short to long chain polypeptides or even glycoproteins (long chain polypeptides bound to carbohydrate e.g. LH/FSH)
are derived from cholesterol with carbon rings structure. They are lipid-soluble and so tend to diffuse through membranes very easily so they are released at the same rate of production.
As they are lipid, they must be bound to a carrier in the blood e.g. albumin and so they are more difficult to clear - they have long half lives so tend to have prolonged effects.
are essentially modified amino acids, derived from tyrosine. The amine hormones can be split into
Thyroid hormones and the Catecholamines.
The thyroid hormones are similar in character to steroid hormones: lipid-soluble, long half live and must be bound to a carrier protein.
The Catecholamines are similar in character to peptide hormones: water-soluble, short half live and circulate unbound.
are more local hormones. They tend to be secreted in a paracrine or autocrine fashion into the intercellular space. Examples of these are prostaglandins and thromboxanes.
The hormones which are lipid-soluble tend to have receptors in the intracellular cytoplasm or nucleus (change gene transcription) as they can easily diffuse into a cell. Whilst, water-soluble hormones tend to have receptors on the cell-surface membrane (rely on secondary messengers).
Steroid hormone receptors alter transcription of genes and can either by cytoplasmic or nuclear.
Steroid hormone receptor
The water-soluble hormones use monomeric receptors, multimeric receptors (insulin dimer receptor) or GPCRs.
The target tissue will have the relevant receptor for the hormone and will
A stimulus stimulates endocrine cells; this stimulus depends on the type of endocrine cell in question. Neurosecretory cells tend to secrete protein/catecholamines whilst Epithelial cells secrete steroid/thyroid.
Almost all hormone cycles have an element of
: the end product/response will reduce it's own production.
Hormones are responsible for development, metabolism, reproduction and for maintaining fluid balance. This means they are vital component of homeostasis.
Hormones are chemical messengers secreted from glands e.g. pituitary gland, adrenals, hypothalamus etc.
Endocrine glands are considered glands with the prime function of producing and secreting hormones.
Glands and hormones
Hormones are delivered to the target tissue namely by four main types of
secretion is when a nerve cell secretes the hormone into the blood. The gland will have neuronal cells with specialised nerve endings containing hormonal vesicles - once excited, the vesicles are released into the blood.
secretion is when the hormone is secreted into the intercellular space to affect adjacent cells.
secretion is when the gland secretes the hormone directly into the blood.
secretion is when the hormone is secreted locally to act on the same cell.
Hormone secretion can be controlled by changes in plasma conc., neurotransmitters or
by another upstream hormone acting on the endocrine cell usually by hypothalamic/pituitary gland
The Pituitary gland is vital and affects salt balance, lactation, growth etc. It consists of two lobes:
Anterior and Posterior
; they are formed from two different embryonic tissues and so differ quite drastically.
The posterior lobe is a growth from the hypothalamus and so contains abundant neural tissue. It contains axons of hypothalamic neurons and their synapses to the bloodstream.
Signals are sent from cell bodies/nuclei (suprsaoptic/paraventricular), these traverse down into the posterior lobe and cause exocytosis of hormone from storage vesicles directly into the blood only ADH (water retention) and Oxytocin (lactation, uterine contractions) etc.
The anterior lobe is a growth from the roof of mouth called Rathke's pouch, therefore it contains little to no neuronal tissue.
Signals are sent from the supraoptic and paraventricular nuclei, these signals go down axons and synapse at the base of hypothalamus. Then, secreting hormone into the pituitary portal blood system at the level of the median eminence which carries the hormone into the anterior lobe stimulating further specific hormone release.
pituitary portal system
is a dense network of capillaries. The superior hypophyseal artery supplies the median eminance whilst the inferior supplies the posterior lobe directly but also the anterior via short portal vessels. With everything draining into venous sinuses.
There are five endocrine cell types within the anterior lobe which can cause further six hormone secretions. There are the
gonadotroph, corticotroph, somatotroph, lactotroph and thyrotroph
cells which each being able to secrete at least one specific hormone to achieve a particular response.
Many of these hormones secreted by the anterior lobe are trophic, encouraging secretion of secondary hormones except prolactin.
The release of these hormones are regulated by
negative feedback loops and hypothalamic hypo-physiological hormones.
The HHPHs are released into the portal blood system from nerve terminals in the median eminence. These stimulate the release of other hormones. The nerve terminals receive inputs from different sources e.g. the Limbic system. These hormones control whether certain hormones are produced from cells in the anterior lobe.
loops help to maintain a set point of a hormone concentration in the blood. These work by end product inhibition; the end product of the endocrine cycle inhibits it's own production and rate of release.
There are types of negative feedback: short-loop feedback, long-loop feedback and ultrashort-loop feedback.
Histology of the Endocrine System
The endocrine system achieves it's effect via hormones. Hormones resemble neurotransmitters but the difference is that - hormones have a widespread effect and disperse in the blood whilst neurotransmitters are local and via synapses.
Exocrine glands differ from endocrine glands:
Exocrine glands rely on acini with apical secretion into a lumen/duct where it is usually release at a body surface.
Endocrine glands rely on secretory cells secreting hormone basally into fenestrated capillaries so the hormone may enter the blood supply.
As there are different classes of hormone (peptide, steroid, catecholamine etc.), the hormone-producing cells are all different.
Peptide hormone cells have abundant rough endoplasmic reticulum, golgi bodies and vesicles. Whilst steroid cells have smooth endoplasmic reticulum, lipid droplets and mitochondria.
The pituitary gland is a vital endocrine gland controlling the release of other hormones from varying organs.
The pituitary gland is very small and is connected to the floor of the third ventricle by the pituitary stalk. It lies posterior to where the optic nerves cross over.
The gland itself lies in a depression in the sphenoid bone called the pituitary fossa. The fossa is lined by dura and covered with a dura sheet (diaphragma sellae); pierced by the pituitary stalk.
The pituitary gland can be split into two distinct regions: the anterior (Adenohypophysis) and the posterior (Neurohypophysis).
The anterior has three parts. The 'pars distalis', 'pars tuberalis' and the 'pars intermedia'.
The 'pars distalis' contains cuboidal, secretory cells clustered around fenestrated sinusoids. These are classified into acidophils, basophils and chromophobes (stem cell).
These groups contain cells such as somatotrophs, gonadotrophs, corticotrophs etc. which secrete particular hormones e.g. growth hormone, prolactin and so on.
The 'pars tuberalis' contains almost entirely gonadotroph cells.
The intermedia contains melanocyte-stimulating hormone which increase skin pigmentation.
The anterior pituitary gland is regulated hypothalamic hormones secreted neuroendocrine cells to release or inhibit hormones. These are secreted into the portal system which end with capillaries bathing the cells of the anterior pituitary.
The portal system helps as it has an immediate response and recycling of hormone elsewhere in the body.
The posterior has two parts.The 'pars nervosa' and the pituitary stalk (also called the infundibulum)
This portion of the pituitary contains just neural tissue. It consists mainly of axons supported by glial-like cells called pituicytes. The cell bodies of the neurons lie in the supraoptic and paraventricular nuclei of the hypothalamus.
The hormones produced by the posterior pituitary gland are ADH (water retention, raises blood pressure in high conc.) and Oxytocin (uterine contraction, lactation etc.)
ADH and Oxytocin are peptide hormones. They are produced in cell bodies in the hypothalamus as a larger protein which is later cleave to the
hormone and binding protein (neurophysin)
. The hormone is carried down axons and released at nerve terminals into fenestrated capillaries. There are aggregations of hormone in the axon called '
They have different embryonic development coming from two different tissues.
The Thyroid gland consists of two lateral lobes connected by a midline called the isthmus. The isthmus lies between the 2nd-4th tracheal rings. In utero, it arises from the diverticulum which bifurcates to give the thyroid.
Cells in the gland are arranged into follicles - a ring of cells arranged in a ring; these secrete thyroglobulin which accumulates as
. This means that the hormone is stored outside of the cell.
The follicular cells take up iodine. This attaches to the tyrosine residues on thyroglobulin. On stimulation by TSH from the anterior pituitary, the follicles endocytose the iodinated thyroglobulin - it is broken down in lysosomes and the derivatives (T3/T4) are released.
The thyroid gland also has scattered parafollicular cells (C cells). These cells are larger - they secrete calcitonin; which reduces calcium mobilization.
The Parathyroid glands exist as two pairs embedded in the posterior border of the thyroid gland.
There are densely packed chief cells arranged in irregular cords. These cells secrete parathyroid hormone which stimulates calcium mobilization.
The adrenal gland sits at the apex of each of the kidneys but are not continuous with the kidney; they are separated by connective tissue.
The glands have two distinct regions which further subdivide into zones. The main two parts are the cortex (outer) and medulla (inner) regions. The have different origin with the medulla being a modified ganglion whilst the cortex is mesothelial.
The cortex secretes steroid so has plentiful smoth endoplasmic reticulum and lipid (cholestrol). The cells are in three zones:
has cells arranged in straight cords running radially. They secrete glucocorticoids mainly cortisol which targets metabolism. Secretion is controlled by adreno-corticotropic hormone via pituitary.
has cells in irregular cords; secrete some glucocorticoid and some sex steroids.
has cells arranged in clusters, surrounded by capillaries. These cells secrete mineralocorticoids mainly aldosterone to increase sodium retention in the DCT regulated by renin.
The medulla has large, polyhedral cells arranged in clumps/clusters. There are also large central veins as blood flows from the cortex into the medulla. They receive cholinergic preganglionic sympathetic input from nerves via the coeliac ganglion.
The chromaffin cells secrete catecholamines on stimulation; mostly adrenaline but also release noradrenaline.
High concentration of glucocorticoids are required to activate the enzyme which converts noradrenaline to adrenaline.
The islets of langerhans are the endocrine portion of the pancreas but are found in the exocrine portion. These are small rounded clusters of cells arranged around capillaries.
There are four main cell types each producing a different hormone.
Adrenal Glands and the Physiology of Stress
The adrenal glands are present on the superior apex of each kidney in a capsule of fat. The cortex secretes steroid hormones whilst the medulla secretes catecholamines.
80% of the gland consists of the cortex. The cortex has the zona glomerulosa, zona fasciculata and the zone reticularis which each secrete individual steroid hormones. (SALT - aldosterone, SUGAR - cortisol, SEX - androgens)
is the main mineralocorticoid. It acts mainly on the DCT and the principal cells of the collecting duct. It promotes sodium retention and potassium excretion by the up-regulation of ENaC and sodium ATPase pumps.
Mineralocorticoids are essential for life as without them, the body can enter circulatory shock because of a marked fall in plasma volume due to excessive sodium excretion.
Aldosterone is stimulated by Renin in response to blood vol./pressure or by direct stimulation of the adrenal cortex by a rise in plasma potassium concentration.
Regulation of aldosterone is independent of the anterior pituitary gland.
The steroids each have a common precursor; cholesterol. This makes steroid hormones fat soluble so they diffuse freely through cell membranes.
Cortisol plays an important role in the metabolism of the major macromolecules. It increases the glucose, amino acid and fatty acid pool.
Cortisol stimulates gluconeogenesis; conversion of non-carbohydrate sources into glucose via the liver. It stimulates protein degradation; commonly in muscle to amino acids and lipolysis; breakdown of lipid stores in adipose to fatty acids.
Cortisol release is mediated by the hypothalamus, anterior pituitary and the adrenals.
Neurones in the hypothalamus send axons to the median eminence. CRH is released from the median eminence into the hypophyseal portal system into the anterior pituitary to control the release of ACTH from the corticotroph cells. ACTH released from the pituitary enters the venous drainage to be taken to the adrenals.
It is regulated by a negative feedback loop. Plasma cortisol inhibits both the hypothalamus (CRH) and the anterior pituitary (ACTH) to inhibit it's own production.
The adrenal medulla has a different histology to the adrenal cortex.
The chromaffin cells are modified sympathetic post-ganglionic nerve fibres. There are no axons however, the cell bodies release hormone directly into the blood when stimulated by pre-ganglionic fibres.
The abundant secretory product is adrenaline (80%) with the other being noradrenaline. The catecholamines are stored in vesicles and release by exocytosis upon stimulation.
The precursor of the catecholamines is tyrosine.
Stress refers to the generalised non-specific response of the body to any factor that overwhelms, or threatens to overwhelm, the body’s compensatory abilities to maintain homeostasis.
Different 'stressors' can cause stress and these can be physical, chemical, emotional, social or physiological.
Stressors are agents which induce stress. Stressor all seem to increase glucocorticoid secretion (Hans Seyle experiments)
The affects of stress are adrenal hyperplasia, atrophy of the immune system and peptic ulcers.
The way in which we respond to stress is called 'General adaptation syndrome'.
The first step is 'alarm'
. This is the immediate, short term response to stress via adrenaline secretion. This is fight or flight.
The hypothalamus responds by activating the SNS and inhibiting PNS. This leads to increased innervation of medulla and more adrenaline in circulation.
This leads to increased glycogenolysis, lipolysis, cardiac output, ventilation and divert blood flow to muscle away from viscera.
The second step is 'resistance'
to this chronic stress. The response is the release of cortisol with cortisol levels elevating by ten times.
If the stress is chronic - the hypothalamus will respond by secreting CRH which will lead to cortisol release. It acts in opposition to insulin causing widespread catabolism; stimulating proteolysis, lipolysis and gluconeogenesis. Cortisol does this by up-regulating metabolic enzyme expression.
Cortisol has clinical importance as it makes it seem that a person may have diabetes. Plus, when diabetics have surgery or major stressors - their insulin intake may need to be modified due to the opposing effects of cortisol.
Cortisol increases the heart's reactivity to catecholamines. This means that chronic stress may cause hypertension or a lack of cortisol may cause hypotension.
Cortisol reduces inflammatory and immune responses by inhibiting prostaglandin and leukotriene production. Inflammatory cytokines cause cortisol release and so, via a negative feedback loop inhibits cytokine production. This is important for anti-inflammatory therapy but prolonged use leads to 'Cushings disease', adrenal atrophy and infections.
May also cause reduced fertility, growth retardation, less muscle mass etc. as a result of excessive cortisol.
The final step is 'exhaustion
'. This leads to immune system failure, illness and even death.
As cortisol is strong catabolic, it leads to the breakdown of the body for gluconeogenesis. This may lead to illness and death.
Addison's disease describes a cortisol deficiency as a result of tuberculosis or autoimmune destruction of the adrenal cortex. This can cause hypotension, hypoglycaemia, weakness, anorexia and primarily - the inability to respond to stress (Addisonian Crisis) which is treated by steroid replacement therapy.