Endocrinology Flashcards
What are hormones?
A hormone is defined as a messenger, carried from an organ from which it is produced, to an organ that it affects, by means of the blood stream. Broadly speaking, there’s 2 types of hormone; peptide hormones and steroid hormones.
How are different types hormones synthesised?
Peptide hormones are synthesised as prohormones, big long peptide chains, which require further processing by special enzymes (e.g. cleavage) to activate. Insulin is a good example of a peptide hormone, as it is created as preproinsulin, a very long biologically inactive precursor which is cleaved by various enzymes to make the biologically active hormone insulin. In contrast steroid hormones are synthesised in a series of reactions from a cholesterol precursor.
How are different types of hormones stored?
Peptide hormones are stored in vesicles, which themselves are stored just beneath the membrane of the cell. They are only released when these vesicles fuse with the cell membrane in response to stimulus - a process called regulatory secretion. In contrast, steroid hormones are released immediately – a process called constitutive secretion - so they’re not stored at all.
How do different types of hormones bind receptors?
Peptide hormones bind to receptors on the cell membrane and they transduce a signal in the target cell using the 2nd messenger system. In contrast, steroid hormones bind to intracellular receptors to change gene expression directly.
Where is the pituitary gland located?
The pituitary gland sits at the base of the brain in a bony dish called the Sella turcica (literally meaning Turkish saddle, due to it unusual shape) of the sphenoid bone. The posterior pituitary gland hangs from the pituitary stalk above it is the hypothalamus. The optic chiasm is where the fibres of the supplying the nasal (medial) retina cross, this is important because a tumour of the pituitary gland can squash the optic chiasm, which can have implications for the patient.
How is information relayed to the anterior pituitary gland?
The anterior pituitary gland does not work by itself but follows the chain of command. It is always told what to do by the hypothalamus, sitting at the top, via hypothalamic parvocellular neurons. These are short neurons that terminate in the median eminence, which is a very vascular part of the hypothalamus. At the end of these neurons, either hypothalamic releasing or inhibitory factors are released into the capillary flexus in the median eminence, where they then diffuse into a group of blood vessels. They can diffuse because these blood vessels are fenestrated (leaky). The hypothalamic regulatory factors are then carried by hypothalamo-pituitary portal circulation to the anterior pituitary gland.
Outline the anatomy of the anterior pituitary gland
The anterior pituitary is anatomically distinct from the hypothalamus and it is not neuronal. Rather, it is made up of hormone containing endocrine cells. There are five different types of hormone containing cells making up the anterior pituitary gland: Somatotrophs, Lactotrophs, Corticotrophs, Thyrotrophs and Gonadotrophs.
Outline the Hypothalamus-Pituitary-Thyroid axis
The thyroid gland sits in the neck like a butterfly and are a perfect example of the chain of command. The thyroid gland does not work by itself but needs to be told what to do by the anterior pituitary gland, which itself is told what to do by the hypothalamus. The axon terminals of the hypothalamic neurosecretory cells release Thyrotrophin Releasing Hormone (TRH), which travels through the fenestrated blood vessels into the blood vessels of the hypothalamus pituitary portal system and then into the anterior pituitary gland. TRH then stimulates the release of Thyroid Stimulating Hormone (TSH)/ Thyrotrophin. TSH then leaves the anterior pituitary gland via the blood supply and is carried to the thyroid gland where it can then stimulate the thyroid gland to release the thyroid hormone (thyroxine).
Which hormones does the anterior pituitary gland release?
There are five cell types that form the anterior pituitary gland, each producing and releasing a unique hormone:
1) Somatotrophs release the Growth Hormone (Somatotrophin)
2) Lactotrophs release Prolactin
3) Thyrotrophs release Thyroid Stimulating Hormone (TSH or Thyrotrophin). 4) Gonadotrophs release Luteinising Hormone (LH) or Follicle Stimulating Hormone (FSH)
5) Corticotrophs release Adrenocorticotrophic Hormone (ACTH or corticotrophin)
How are the different hormones released by the anterior pituitary gland regulated?
1) Growth hormone is special because it is the only hormone regulated by an ‘on and off switch.’ The on switch (the hypothalamic stimulus) which causes growth hormone released from the anterior pituitary gland is called Growth Hormone Releasing Hormone (GHRH). The off switch (the hypothalamic inhibitor) for growth hormone is called Somatostatin (somato = growth, statin = stop).
2) Prolactin is also quite special because it only has an inhibitor control in dopamine. In other words, lots of dopamine means less prolactin, and vice versa.
3) Thyroid stimulating hormone (TSH) is stimulated by Thyrotrophin Releasing Hormone (TRH).
4) Luteinising hormone (LH) and Follicle Stimulating Hormone (FSH) are regulated by the hypothalamic factor Gonadotropin Releasing Hormone (GnRH).
5) Adrenocorticotrophic Hormone (ACTH) is regulated by the hypothalamic factor Corticotrophin-Releasing Hormone (CRH).
What are the main target cells of the anterior pituitary hormones?
1) Growth Hormone works particularly on the liver (contains many Growth Hormone receptors), but also on skeletal muscle and bone.
2) Prolactin works very specifically for lactation postpartum.
3) Thyrotrophin (or Thyroid Stimulating Hormone – TSH) works to tell the thyroid gland what to do.
4) The Gonadotrophins (LH and FSH) instruct the gonads (testes in males and ovaries in females) to work.
5) Adrenocorticotrophic Hormone (ACTH) travels to the adrenal gland, which tells the adrenal cortex, sitting on top of each kidney, what to do.
What condition caused by a tumour results in impaired peripheral vision?
Sometimes patients with a problem with their pituitary gland can present with problems that aren’t hormonal. For instance, the optic chiasm, being very close by to the anterior pituitary gland, separated by a couple of millimetres, can be squashed if there is a growth in the anterior pituitary gland. This can cause a visual problem called a bitemporal hemianopia, leading to the peripheral half of the visual field being cut off. An assessment of visual field can be performed, wherein a patient must press a button every time that they see a light flashing. Hence, a bitemporal hemianopia is a very common symptom of a pituitary tumour having grown out of the Sella turcica and having squashed the optic chiasm.
What is the optic chiasm?
The optic chiasm is where the fibres that supply the nasal (medial) part of the retina, and hence the temporal visual fields, crossover. So, the presence of a pituitary tumour/suprasellar here would squash and compress these fibres which are supplying the nasal retina, causing the temporal visual field on each side to be affected, as it prevents the transmission of sensory information from lateral visual fields to the occipital lobe.
Outline the mechanism of milk production and secretion
The mechanical stimulation of an infant latching on to the breast activates afferent ascending sensory pathways. The afferent signals are then integrated in the hypothalamus and inhibit dopamine release from dopaminergic. Less dopamine in the hypothalamo-pituitary portal system causes less inhibition of anterior pituitary lactotrophs, as Prolactin is the only anterior pituitary hormone which is regulated only by inhibition. The increase in plasma Prolactin increases milk production and secretion in mammary glands.
Outline the mechanism of Growth Hormone action
Growth Hormone, as the name suggests, regulates gross growth of muscles. Thus, it can be a drug of among certain athletes. It regulates muscle growth in one of two ways: either by binding directly to growth hormone receptors on muscle or bone or by stimulating the liver to produce the hormone Insulin-like Growth Factor (IGF). In adults and children IGF-1 is the main Insulin-like Growth Factor that’s produced, IGF-2 is more important in the developing foetus. IGF-1 can also bind receptors on muscle and bone, thereby stimulating growth.
What is Gigantism?
Gigantism occurs when too much growth hormone is produced before puberty is finished. The reason why the condition occurs only before the end of puberty, is because during puberty epiphyseal growth plates, the growth plates at the end of long bones like the femur like and humerus, are not fused, only fusing at the end of puberty when adult height is reached. Gigantism can be treated with an operation, but we can’t can manipulate hormones by using a drug like a somatostatin analogue to stop the release of the growth hormone.
What is Acromegaly?
Acromegaly is an overproduction of Growth Hormone occurring after puberty, so does not result in an increase in height. However, lots of other changes do occur, including: a coarsening of facial features, an enlarged nose, enlarged lips, macroglossia, prognathism (enlarged mandible/jaw) which can cause gaps to form between teeth, enlarged hands and feet, sweatiness and headaches.
Outline the anatomical differences between the anterior and posterior pituitary glands
The posterior pituitary gland is very different to the anterior pituitary gland, not just in the hormones that it produces, but also in terms of what it’s made of. Embryologically the anterior pituitary grows up, developing from the base (the roof of the mouth), while the posterior pituitary gland develops downward, making it anatomically continuous with the hypothalamus. As well as this, unlike the anterior pituitary, the posterior pituitary is made of hypothalamic magnocellular neuronal tissue.
Which hormones are produced by the posterior pituitary gland?
There are only 2 hormones produced by the posterior pituitary gland: Arginine vasopressin (AVP, also known as Anti-diuretic hormone) and Oxytocin. The hypothalamic magnocellular neuronal tissue that form the posterior pituitary gland, are long neurons that originate in supraoptic (AVP) and paraventricular (oxytocin) hypothalamic nuclei. The hypothalamic hormones flow from the hypothalamic nuclei, down the pituitary stalk to the posterior pituitary, where they then diffuse into blood capillaries.
What are the physiological functions of Arginine vasopressin (AVP)?
The main physiological action of Arginine vasopressin (AVP or Anti-diuretic hormone), diuresis referring to the production of urine, is the stimulation of water reabsorption in the renal collecting duct to concentrate urine. It works through the V2 receptor in the kidney and as a vasoconstrictor via the V1 receptor. It also stimulates Adrenocorticotrophic Hormone (ACTH) release from the anterior pituitary, although ACTH’s main stimulus remains Corticotrophin Releasing Hormone (CRH) in the anterior pituitary.
What is the role of Arginine vasopressin (AVP) in urine concentration?
Arginine vasopressin moves from blood supply, through the basolateral membrane and binds to V2 receptors on the collecting duct cells. The binding of Arginine vasopressin to the V2 receptor stimulates an intracellular signalling cascade which results in the movement Aquaporin-2 channels, which can insert into certain membranes, to allow the movement of water through. The aquaporin-2 channels are transported to the apical membrane, itself in contact with the urine flowing through the nephron. Here, water is absorbed through the Aquaporin-2 channels down the concentrating gradient, across the collecting duct cell and exits the cell via an aquaporin 3 channel. The water is then reabsorbed into systemic circulation, leaving more concentrated urine.
What are the functions of Oxytocin?
The hormone oxytocin has two jobs:
1) Its first biological role is during labour (parturition). During labour, the uterus is made up of very specific muscle myometrial cells and these cells contract in order to propel the baby out of the uterus. Oxytocin stimulates myometrial cells to contract very powerfully. An analogue of oxytocin is also used in labour to try and aid with women struggling in delivery.
2) Its second role is in milk expulsion. Following mechanical stimulation of the nipple, an ascending afferent sensory pathway is activated. The afferent signal is integrated in the hypothalamus and stimulates oxytocin releasing neurone activity by hypothalamic magnocellular neurons in the posterior pituitary. Action potentials then travel down the oxytocin neurons and oxytocin is secreted into the blood stream. Increased plasma oxytocin stimulates myoepithelial cells in the mammary glands to contract and to expel milk to the baby.
What are the symptoms and clinical features of hypothyroidism?
Untreated hypothyroidism is an endocrine emergency that often presents symptoms of drowsiness, confusion, memory impairment, fatigue, cold intolerance, constipation, depression, low sexual desire and tiredness. Clinical features include very thin hair, a receding hairline, puffy eyelids, dry lips, very thick and dry skin, overgrown thickened toenails, bradycardia (slow heart rate) and non-pitting edema (swollen area of skin that does not indent when pressed). These patients often eventually develop myxoedema coma, which is a life-threatening complication, that does not necessarily require them to fall into an coma. Hypothyroidism is often treated with intravenous thyroid hormone treatment and tablets.
Outline the anatomy of the thyroid gland
The thyroid gland is found in the neck and can be felt moving up when swallowing. The thyroid is a ‘butterfly’ shaped gland found on the trachea, just beneath the thyroid cartilage (Adams Apple). It is made up of two lobes (the right lobe and the left lobe) and the Isthmus, which is the medial between the lobes. Approximately 10-30% of people have an extra lobe just above the Isthmus, called the Pyramid lobe, which is an embryological remnant. The thyroid gland is made up of follicles, which are small spherical structures made of follicular cells surrounding a colloid - a sticky mucus like extracellular fluid where the thyroid hormone is synthesised, in close proximity to blood vessels through the basolateral membrane, Around follicles can be found parafollicular cells which are even smaller cells, responsible for the production of calcitonin.
Which key anatomical structure lie close to the thyroid gland?
The thyroid gland is very close to other very important structures. There are two (superior and inferior) parathyroid glands on the back of each lobe of the thyroid, which produce the parathyroid hormone responsible for calcium metabolism. The thyroid is also in close proximity to the recurrent laryngeal nerve, the nerve supplying vocal cords. Operations to remove the thyroid gland (thyroidectomy) must be done very delicately as they risk damage to both the recurrent laryngeal nerve and the parathyroid glands.
How does the thyroid develop embryologically?
Embryologically, the thyroid gland originates from midline of the pharynx (near the base of the tongue). A thyroglossal duct then develops, descending from the tongue down, before dividing into two lobes. The duct then disappears leaving the Foramen caecum, an embryological remnant, seen as a very small dot at the back of the throat. The thyroid arrives at its final position within the neck by week 7 of gestation, after which the actual gland develops.
How is the thyroid hormone produced?
The colloid is found at the centre of follicles, adjacent to follicular cells. Within each follicular cell, is a nucleus and lysosomes. Blood vessels lie in close proximity to the follicular cells, whose cell membrane contains a Thyroid Stimulating Hormone receptor (TSH-R).
1) The TSH arrives through the systemic circulation, via the blood, and binds specifically to TSH-R on the follicular cell.
2) Simultaneously, sodium (Na+) and iodide (I-) ions arrive via the blood, entering the follicular cell via the sodium-iodide co-transporter.
3) The iodide ions are taken in cross the follicular cell and they go through the transporter on the other side of the cell, and into the colloid.
4) When TSH binds TSH-R, a prohormone called thyroglobulin (TG) is released and enters the colloid, whilst the thyroid peroxidase enzyme (TPO) is also activated. This enzyme is important in the production of the thyroid hormone as it acts alongside hydrogen peroxide to catalyse the two iodination reactions in the colloid.
5) In the first iodination reaction, iodide ions are oxidised to yield iodine (catalysed by TPO+H2O2).
6) The iodine is then reacted with TG, in a second iodination reaction (catalysed by TPO+H2O2), to give monoiodotyrosine (MIT) and diiodotyrosine (DIT).
7) MIT and DIT, joined together by a coupling reaction (catalysed by TPO+H2O2), give thyroid hormone (T3 and T4), still bound to TG.
8) The thyroid hormone then enters the cell where, in lysosomes, the protein bonds are broken down, allowing T3 and T4 to enter the bloodstream and leave TG behind.
How many tyrosine residues can be iodinated?
Tyrosine is an amino acid with an aromatic ring, of which there are ~100 tyrosine residues, but only ~20 have the capability of being iodinated, meaning that an iodine group can be added to them.
The coupling reactions of which molecules produce T3 and T4?
3-monoiodotyrosine (MIT) and 3,5-diiodotyrosine (DIT) can be produced by iodinating tyrosine. Joining 3-monoiodotyrosine (MIT) and 3,5-diiodotyrosine (DIT) by a coupling reaction gives 3,5,3’-tri-iodothyronine (T3), which is the active thyroid hormone. Joining DIT with another DIT gives a different type of coupling reaction producing 3,5,3’,5’-tetra-iodothyronine (T4), also known as Thyroxine.
What is the difference between T3 and T4?
Essentially, the only difference between the T3 and T4 is the absence of the iodide group at position 5’ in T3.
How are most of T3 and T4 produced?
Thyroxine (T4) is the main prohormone product of the thyroid gland, only being deiodinated by deiodinase enzymes to T3, its bioactive metabolite form, providing almost all of the thyroid hormone activity in target cells. Only 20% of circulating T3 comes directly from secretion from the thyroid gland, the remaining 80% comes from the deiodination of T4. Reverse T3 is an inactive form of T3 that occurs when T4 is deiodinated at the position.
How is thyroid hormone transported?
The vast majority of thyroid hormone is transported in the blood, bound to plasma proteins. 70-80% of thyroid hormone is bound to the plasma protein Thyroid-binding Globulin (TBG). 10-15% of thyroid hormone in the blood is bound to the plasma protein Albumin. Some thyroid hormone is also bound to Prealbumin/Transthyretin. Only 0.05% of T4 and 0.5% of T3 is unbound, meaning that they are free to act as bioactive agents in the target tissues.
How does thyroid hormone effect gene expression?
T3 and T4 effect gene expression by entering the cell within the target tissue, through their respective receptors. The T4 is deioidinated by deiodinase enzymes, within the cell, converting it to the active thyroid hormone T3. T3 then enters the nucleus, containing the Thyroid Responsive Element (TRE), binding to the Thyroid Hormone Receptor on its surface. This allows it to alter gene expression, by activating or repressing gene transcription.
What is Cretinism?
Cretinism is a condition of untreated congenital hypothyroidism, arising from either a complete lack of a thyroid gland or a lack of any thyroid hormone that functions or poorly developed thyroid hormone. Babies with the condition appear unhappy, drowsy and quite puffy. A heel prick test is done at 5 days of age, allowing a few drops of blood to be removed. The blood can then be used to detect Phenylketonuria (PKU), an inborn error of metabolism, as well as for a measurement of TSH, to determine the presence of an under active thyroid. A high level of TSH could suggest congenital hypothyroidism and thankfully lifelong thyroid hormone replacement treatment is available. When the baby is in utero, thyroid hormone, from the mother, crosses the placenta, protecting it while it is growing. Hence, the thyroid hormone deficiency only becomes apparent when the baby is delivered.
Why does autoimmune damage to the thyroid gland increase levels of TSH?
Autoimmune damage to the thyroid reduces its ability to produce T4 and T3, and as a result thyroxine levels drop; hence, the anterior pituitary is stimulated to release TSH, causing its levels to climb.
What is the physiological impact of thyroid hormone?
The thyroid hormone increases basal metabolic rate, meaning the amount of energy or calories that every cell in the body requires to function. It also effects metabolism by increasing glucose absorption, glycogenolysis, gluconeogenesis and fat metabolism. As well as this, the thyroid hormone can also affect the sympathetic nervous system, by potentiating the reactions of catecholamine and thus raising cardiac output. It also has effects on the gastrointestinal (GI) tract and the maturation of the CNS, as well as bone maturation.
What is the half life of thyroid hormone?
The half-life of T4 is ~7 days ad ~2 days for T3.
How the the hypothalamus-pituitary-thyroid axis control thyroid hormone production?
The Hypothalamus-pituitary-thyroid axis is important because it allows the production of thyroid hormone to be controlled by negative feedback. The TRH released from the hypothalamus tells the anterior pituitary to release TSH, which is released into circulation. It the acts on the thyroid gland to stimulate the release of T3 and T4, and when there’s sufficient T3 and T4, signals are sent back to both the hypothalamus and anterior pituitary, switching them off. Somatostatin, produced in the hypothalamus, can inhibit the production of TSH. Large quantities of iodide can inhibit the production of T3 and T4, known as the Wolff-Chaikoff effect. In fact, potassium iodide is sometimes used to treat hyperthyroidism.
Which sex is more predisposed to thyroid disorders and why?
Women are more predisposed to thyroid disorders (4:1 ratio) than men, as their immune systems have had to evolve to carry babies, who carry a wide range of antigens, that women are exposed to. This had made their immune systems slightly different to men’s and thus more predisposed to autoimmune diseases, such as thyroid disorders.
What is the difference in the incidence of hypothyroidism and hyperthyroidism?
The incidence of hypothyroidism and hyperthyroidism is exactly the same.
What are the most common forms of autoimmune thyroid disorders?
The most common forms of autoimmune thyroid disease are Hashimoto’s thyroiditis, usually associated with hypothyroidism, and Graves’ disease, usually associated with hyperthyroidism, but in rare cases can also cause hypothyroidism.
How does the presence of one autoimmune disease impact the risk of others?
The presence of one autoimmune disease increases the risk of others. For instance, patients with vitiligo or pernicious anaemia, which are other autoimmune conditions not specifically related to thyroid, are going to be more at risk of developing autoimmune thyroid disease than the general population.
What is Levothyroxine?
Levothyroxine is a synthetic tablet of T4 that can be deiodinated in exactly the same way and to produce T3.
Which through diseases is Levothyroxine prescribed for?
Levothyroxine is mainly prescribed for hypothyroidism, but it is also prescribed for hyperthyroidism.
What is the “block and replace” regimen?
For hyperthyroidism, anti-thyroid drug, called Carbimazole, can be prescribed, that stops any production of thyroid hormone. Hence, a “block and replace” regimen is used, wherein, a high dose of Carbimazole is used, to block all thyroid hormone production, then Levothyroxine is given to replace the thyroid hormone lost.
How is the amount of Levothyroxine administered determined?
The amount of Levothyroxine given depends on the amount of TSH and T4 found during the blood test. In a patient presents with hypothyroidism high TSH and low T4 levels would be expected. A prescription of levothyroxine would be given, and ~ 3 months later blood tests would be repeated. At that stage, hopefully, the thyroid hormone levels have gone and the TSH levels have come back into the normal range. The most common dose of Levothyroxine is ~ 100 micrograms but may be lower in very elderly patients or those at risk of ischemic heart disease. It is usually administered orally and only in emergency situations, like a myxoedema coma, that intravenous thyroid hormone replacement is considered.
What are the complications and side effects of Levothyroxine?
Complications and side effects of Levothyroxine are very rare. Minor complications arise when the thyroid hormone replacement is overdone, which may cause weight loss and headaches. A major complication may be tachycardia (a rapid heart rate, which may cause a heart attack, but these are incredibly rare.
Why is T3 not prescribed to patients, by itself?
T3 is not usually prescribed to patients as there’s no evidence that it works any better than T4, and it is much more expensive to manufacture. Additionally, target tissues have your deiodinase capable of deiodinating T4 into T3. However, there are reports in the literature that combining both T3 and T4, may cause some people feel to better. However, patients may render themselves thyrotoxic and symptoms such as: palpitations, tremors, anxiety. This is because, often when you give T4 and T3 together TSH may be suppressed as anterior pituitary thyrotroph cells are switched off, due to an excess of thyroid hormone.
What is Graves’ disease?
Graves’ disease is an autoimmune disease that causes antibodies to bind and stimulate the TSH receptor in the thyroid, causing the whole gland to enlarge and nodules that appear for no specific reason. Normally TSH receptors in follicular cells, in the thyroid, are stimulated by the arrival of TSH from the anterior pituitary, but antibodies can develop that bind and stimulate this receptor. This results in the TSH receptor being activated, resulting in the overproduction of T4 and T3, causing a smooth toxic multi nodular goitre. Other antibodies bind to muscles behind the eye, causing Exophthalmos (bulging eyes), whilst others stimulate the growth of soft tissue on shins causing Pretibial myxoedema.
What are the symptoms and clinical features of hyperthyroidism?
Untreated hypothyroidism is an endocrine emergency that often presents symptoms of anxiety, dry eyes, heat intolerance, myopathy (muscle weakness), mood swings, diarrhoea and palpitations. Clinical features include a smooth goitre, a smooth enlargement of your thyroid gland, weight loss, tremoring hands, exophthalmos (bulging eyes) and pretibial myxoedema (thick, red skin).
Where are the adrenal glands located?
The adrenal glands are located above the kidneys.
Which blood vessels connect to the adrenal glands?
The left adrenal gland connects to the left adrenal vein , which drains into the renal vein. The right adrenal artery connects to the right adrenal vein, which drains into the inferior vena cava (IVC). Both adrenal glands are supplied by many (57) arteries, but each is supplied by only one adrenal vein.
Outline the microanatomy of the adrenal cortex
In the centre of each adrenal gland, lies the adrenal medulla, composed of neuroendocrine/chromaffin cells. Outside the adrenal medulla, lies the adrenal cortex, composed of 3 different layers:
1) Zona reticularis: a thin layer, surrounding the adrenal medulla
2) Zona fasciculata: a thick layer, surrounding the zona reticularis
3) Zona glomerulosa: the outer most layer of the adrenal gland
Which hormones are secreted by the adrenal medulla?
The adrenal medulla is derived from the ectodermal exclusively secretes catecholamines. 80% of the catecholamine that it secretes is adrenaline/epinephrine. The remaining 20% is noradrenaline/norepinephrine, “nor-“ meaning without a methyl group. Catecholamines are stored in the cytoplasmic granules and released in response to acetylcholine (Ach) from preganglionic sympathetic neurons.
How are catecholamines synthesised?
1) Tyrosine is the precursor for these catecholamines. Oxidising (add O2) tyrosine produces dihydroxyphenylalanine (DOPA).
2) Decarboxylating (removing CO2) DOPA produces dopamine, which is important for blood pressure control.
3) Dopamine is then converted to noradrenaline/norepinephrine.
4) Methylating (adding “-CH3” methane group) noradrenaline/norepinephrine produces adrenaline/epinephrine.
What is the function of adrenaline?
Adrenaline/epinephrine plays a role in blood pressure control, as well as the “fight or flight” response, as it causes heart rate to increase, as well as sweating.
Which hormones are secreted by the adrenal cortex?
The adrenal cortex makes three groups of steroids. The zona glomerulosa makes mineralocorticoids, the key one in humans being aldosterone. The zona fasciculata makes glucocorticoids, which mainly impact glucose metabolism, such as cortisol, as well as some sex steroids, such as androgens (“male” sex hormones) and oestrogen (female sex hormone). However, most sex hormones come from the sex organs (the ovaries and testes).
Why is the zona fasciculata much larger than the zona glumerulosa?
The zona fasciculata is so much larger than the zona glomerulosa, as there is much more cortisol in blood than aldosterone. Cortisol is measured in nanomoles per litre (nmol/L) whereas aldosterone is measured in picomoles per litre (pmol/L), as there is 100x more cortisol in circulation, than aldosterone. The zona reticularis is disappearing in humans, but also contributes to the production of cortisol.
Which structures of the adrenal cortex can be distinguished under a microscope?
When the adrenal cortex is magnified, a capsule can be seen on the outside. The zona glomerulosa and zona fasciculata look very similar under direct microscopy, until they’re stained which allows the difference in their cellular structures to be better seen.
Which molecule is the precursor of all steroids?
The precursor of all adrenal cortex secretions is cholesterol, so a steroid is a hormone which is based on the cholesterol molecule. Cholesterol traditionally has numbers, which are used to label the enzymes that convert cholesterol into the steroids hormones.
What are enzymes?
An enzyme is a protein that catalyses a specific reaction and there are many different enzymes. Specific enzymes catalyse the synthesis of particular alterations to a molecule.
In what ways is a fall in blood pressure detected?
A fall in blood pressure is detected by:
1) Decreased renal perfusion pressure (normally associated with decreased arterial blood pressure).
2) Increased renal sympathetic activity (direct to Juxtaglomerular apparatus cells which secrete renin)
3) Decreased sodium (Na+) load to the top of the loop of Henle (Macula Densa cells, above which sit the Juxtaglomerular apparatus cells).
How does renin help lower blood pressure?
When blood pressure is high, renin is suppressed, but when blood pressure begins to fall, renin is released into the circulation. Renin acts by switching on a cascade that converts a basic protein called Angiotensinogen, produced in the liver, into the protein Angiotensin I. Angiotensin Converting Enzyme (ACE) then converts this to Angiotensin II. Angiotensin II regulates aldosterone release from the adrenal glands, by switching on the 5 enzymes in the zona glomerulosa needed to produce aldosterone from cholesterol.
How is aldosterone synthesised?
1) When making aldosterone (a mineralocorticoid), the cholesterol side chain is cleaved off, by the cholesterol side-chain cleavage enzyme (P450scc), forming pregnenolone.
2) Pregnenolone is then dehydrogenated (oxidised) in position 3, containing the “-OH” group, to a ketone called progesterone, by the enzyme 3beta-hydroxysteroid dehydrogenase (3b-HSD). Progesterone is generally a hormone that comes from the ovary, but it also a precursor of other steroids, in the adrenal gland.
3) Progesterone is then hydroxylated (“-OH” group added), in position 21, using the enzyme 21 Hydroxylase, forming the hormone 11 deoxycorticosterone.
4) 11 deoxycorticosterone is itself then hydroxylated in position 11, forming corticosterone, by the enzyme 11 hydroxylase.
5) Finally, corticosterone is hydroxylated in position 18, using the enzyme 18 hydroxylase, to form aldosterone.
How does aldosterone help maintain blood pressure?
Aldosterone stimulates sodium (Na+) reabsorption in the distal convoluted tubule and the cortical collecting duct of the kidneys (as well as in sweat glands, gastric glands and the colon):
1) Sodium leaves the urine filtrate, while aldosterone switches on sodium/potassium-ATPase.
2) This causes potassium (K+) to be excreted into the urine filtrate, as sodium and water are reabsorbed into the blood.
3) This raises the blood volume, thus maintaining blood pressure, for instance after being stabbed.
What is cortisol?
Cortisol is a stress hormone, helping to maintain survival by changing the energy is used.
