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Clinical Practice Keywords / /Homoeostasis Systems of This article has been Endocrine system double-blind peer reviewed In this article... ● The difference between endocrine glands and exocrine glands ● Major endocrine glands and their hormones ● The role of hormones in physiological processes and homoeostatis

Endocrine system 1: overview of the endocrine system and hormones

Key points Author John Knight is associate professor in biomedical science, College of The endocrine and Sciences, Swansea University. system comprises glands and tissues Abstract The endocrine system is made up of glands and tissues that produce and that secrete secrete hormones to regulate and coordinate vital bodily functions. This article – the NT SELF- hormones to first in an eight-part series on the and of the endocrine system ASSESSMENT regulate and – explores the nature of endocrine glands and tissues, and the role of hormones as coordinate vital chemical signals that are carried in the blood. It also highlights the varying roles of functions in the hormones in regulating and coordinating physiological processes, as well as maintaining homoeostasis in the body. Endocrine glands differ from exocrine Citation Knight J (2021) Endocrine system I: overview of the endocrine system and glands by releasing hormones. Nursing Times [online]; 117: 5, 38-42. their secretions directly into the bloodstream, rather he endocrine system is a series of ”, secreting a cocktail of chemical sig- than a central duct glands and tissues that produce nals that further influences human physi- and secrete hormones, which are ology (O’Callaghan et al, 2016). Endocrine glands’ Tused by the body to regulate and highly vascular coordinate vital bodily functions, including Endocrine and exocrine glands nature allows growth and development, metabolism, By definition, all glandular tissues pro- variables in the blood sexual function and reproduction, and duce secretions. Most glandular structures to be monitored mood. This article – the first in an eight-part are epithelial in origin, and many are continuously and series on the anatomy and physiology of the folded and organised into recognisable appropriate endocrine system – provides an overview of glands with a central duct. Glands pos- hormones to be the system, focusing on endocrine glands sessing a duct are exocrine glands (Fig 2); rapidly released into and tissues, and the role of hormones as the duct acts as a conduit into which secre- the circulation chemical signals that are bloodborne. It also tions are released before being carried explains the diverse roles of hormones in away to their sites of action. Exocrine Hormones exert their regulating and coordinating physiological glands include many of the digestive physiological effects processes, and maintaining homoeostatic glands in the gut, sweat glands in the by binding to balance in the body. and -producing glands in the specific receptors The endocrine system (Fig 1) is incred- mucous membranes of the and associated with their ibly complex: it consists of dedicated, spe- reproductive tracts. target cells cialised endocrine glands – such as the thy- In contrast, endocrine glands have no roid, parathyroids and adrenal glands duct, but release their secretions, called Hormones regulate – together with tissues such as (adipose hormones, directly into the blood (Fig 2). physiological ) and that have a secondary For this reason, most endocrine glands are processes and are endocrine function and also secrete a range highly vascularised, and many of their key to maintaining of hormones. It has been suggested that the component cells are in direct contact with homoeostatic microbial biome (the diverse plethora of blood . This close association balance in the body micro-organisms colonising the human with blood vessels facilitates the direct body) also functions as a “virtual endocrine release of hormones into the blood and

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Fig 1. Major endocrine glands and tissues, and their hormones glands. As an example of this, adrenocorticotropic regulates the release of the long-term stress Hypothalamus Melatonin hormone, cortisol, from the adrenal GHRH, TRH, CRH, cortex. somatostatin, , As the pituitary gland regulates hor- vasopressin TSH, LH, GH, ATCH, MSH, vasopressin, prolactin, oxytocin mone release from other endocrine glands, and parathyroid it is often referred to as the ‘master’ gland. PTH, T3 and T4, This is something of a misnomer as the calcitonin Thymopoietin release of stimulating hormones from the Ghrelin, gastrin, neuropeptide pituitary gland is, itself, under the control IGF, THPO Y, histamine, somatostatin, of hormones produced by the hypothal- amus; this will be explored in Part 2. Insulin, glucagon, somatostatin Adrenaline, noradrenaline, Thyroid gland and associated androgens, glucocorticoids and parathyroids Oestrogens, progesterone The thyroid is a bilobed (two-lobed) organ Testes Oestradiol, androgens, that resembles a bow tie in shape; it typi- inhibin Relaxin, prolactin cally weighs 25-30g and is located just below the (Dorion, 2017). The thy- TSH (Thyroid stimulating hormone); LH (luteinising hormone); GH (growth hormone); ATCH (adrenocorticotrophic hormone); MSH (melanocyte-stimulating hormone); roid itself has two major populations of GHRH (Growth hormone-releasing hormone); TRH (thyrotrophin-releasing hormone); endocrine cells: CRH (corticotrophin-releasing hormone); PTH (parathyroid hormone); l  IGF (insulin-like growth factor); THPO (thrombopoietin) Follicular cells – these produce the iodine-containing hormones triiodothyronine (T3) and allows the blood to be continuously moni- Indeed, the hypothalamus can be tetraiodothyronine (T4, also known as tored for physiological changes that can of as the key crossover point between the thyroxine), which regulate the body’s initiate hormone release. As an example of and the endocrine system. metabolism; this, the insulin-producing cells of the l Parafollicular cells – these produce the pancreas will release insulin when they The pituitary gland hormone calcitonin, which helps to detect an increase in blood–glucose con- The pituitary gland is a pea-sized struc- regulate blood– concentration. centration after the consumption of carbo- ture, typically weighing around 500mg; it The parathyroid glands are found hydrate-rich food. is located at the base of the , just embedded in the posterior portion of the The highly vascular nature of endocrine behind the nasal cavity, where it is pro- glands also allows for the delivery of sig- tected by the sphenoid bone of the Fig 2. Endocrine and exocrine nals (usually other hormones) from other (Ganapathy and Tadi, 2020). It has two glands glands to regulate release of their own hor- major regions: mones. For example, the thyroid gland l The posterior (back portion) – releases hormones that regulate metabo- essentially, an extension of the lism, such as thyroxine, in response to the hypothalamus, the posterior of the Hormone thyroid-stimulating hormone, which is pituitary gland stores and concentrates secretion produced by the anterior pituitary gland. two neuropeptide hormones called Blood anti-diuretic hormone (ADH) and Thyroid flow The major endocrine glands oxytocin, which are produced by the (endocrine) Fig 1 shows the position of the major endo- ( cells) of the gland crine glands in the body; however, it is hypothalamus. ADH helps regulate Endocrine important to be aware that many other fluid balance and , while organs and tissues have a secondary endo- oxytocin – among other things – crine function, including the , kid- initiates parturition (). 2a. Thyroid (endocrine) gland neys, bone and adipose tissues (Knight et l The anterior (front portion) – this Sweat (exocrine) gland al, 2020; Moser and van der Eerden, 2019). develops from the epithelial tissues in the roof of the embryonic oral cavity, The hypothalamus which bulges up into the skull, fusing The hypothalamus is a vital region of the with the posterior pituitary. It produces Duct brain, which plays an important role in: several key hormones such as l Thermoregulation; somatotropin (growth hormone) and Skin Exocrine l  Behavioural and emotional responses; melanocyte-stimulating hormone, cells l Regulation of appetite; which helps to regulate skin l Coordination of the autonomic nervous pigmentation. The anterior pituitary system; also produces several stimulating l Generating a range of hormones that hormones that control the release of 2b. Sweat (exocrine) gland

JENNIFER N.R. SMITH JENNIFER regulate the activity of endocrine glands. hormones from other endocrine

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thyroid gland. Most people have four para- Fig 3. Receptors for peptide and steroid hormones thyroid glands (explored in Part 3); these produce parathyroid hormone, which works antagonistically to calcitonin during calcium homoeostasis.

Peptide Membrane Steroid Pancreas Intracellular hormone receptor hormone The pancreas is a vital organ in both the receptor digestive and the endocrine systems; residing in the U-shaped loop of the duo- denum, it is typically 14-23cm in length and weighs around 100g (Longnecker, 2021). Second The endocrine portions of the pancreas messenger are known as the islets of Langerhans, which are small islands of glandular tissue Plasma Plasma found throughout the structure of the Cellular membrane membrane Cellular pancreas. The contain response response several types of endocrine cells, including: 3a. Peptide hormone 3b. Steroid hormone l Alpha cells, which produce glucagon; l Beta cells, which produce insulin. These two hormones – glucagon and Once a follicle ruptures and releases its these receptor sites, either to mimic the insulin – play a key role in regulating mature ovum into the fallopian tube actions of hormones (for example, in the blood–glucose concentration, which will during , the remnants of the fol- case of a hormone deficiency such as hypo- be discussed in the section on homoeo- licle collapse into a structure called the thyroidism, which is treated with levothy- stasis later in this article. corpus luteum (yellow body). This pro- roxine) or to act as competitive antagonists duces the second major female sex hor- to physically block the receptor, pre- Adrenal glands mone, progesterone, which prepares the venting the natural hormone from binding There are two adrenal glands – one above endometrium for implantation of a ferti- and exerting its effect. Hormones can be each . They are roughly triangular in lised ovum (zygote) and, subsequently, broadly divided into three major classes: shape, around 3cm in width and each maintains the integrity of the endometrial l Peptide hormones; weighs 4-6g (Lack and Paal, 2020). Adrenal lining, should implantation occur. l Steroid hormones; glands have two major regions: The testes () are the paired pri- l Amino acid-derived hormones. l Adrenal cortex (outer region) – this mary reproductive organs in males, produces steroid hormones, including responsible for producing spermatozoa. Peptide hormones the long-term stress hormone cortisol, They are oval shaped and, in males, These are the largest hormones, with rela- aldosterone (which regulates the levels are typically 4.5-5.1cm long and weigh tively high molecular weights. They are of and in the blood) 15-19g (Silber, 2018). Each testis contains a proteinaceous chemical signals, com- and a group of testosterone-like specialised group of endocrine cells called prising chains of amino acids of varying hormones called androgens; interstitial cells, which produce the male lengths. Examples include: l Adrenal medulla (inner region) – this sex hormone testosterone. This is an ana- l Somatotropin (growth hormone); produces adrenaline (epinephrine) and bolic steroid produced in greater amounts l Insulin; noradrenaline (). These during , when it promotes muscle l Ghrelin (the hunger hormone). ‘fight-or-flight’ hormones – that are development, growth of facial and body Some peptide hormones are initially usually produced when a person is , and expansion of the larynx, leading produced as inactive forms called prohor- under threat, afraid or excited – to a deepening of the voice. mones; a good example is insulin, which is function primarily to activate the first synthesised as a much larger mole- sympathetic branch of the autonomic Hormones as chemical signals cule, called proinsulin, and then cleaved nervous system and prepare the body Hormones are traditionally defined as into its active, shorter form before being for immediate action. chemical signals, transported to their released into the blood. target tissues in the blood; today, however, Peptide hormones tend to exert their and testes that definition is often expanded to effects by binding to receptors on the surface The ovaries are the primary reproductive include all chemical messengers that bind of the plasma membranes of target cells, as organs in females, responsible for pro- to target cells with high affinity. So far, shown in Fig 3. This triggers a variety of ducing ova. Mature ovaries are fairly irreg- more than 100 hormones have been identi- transmembrane events, leading to the pro- ular, lumpy and almond shaped, typically fied in the , and this rises to duction of second messengers (such as cyclic 3-5cm long and weigh 5-8g, although they more than 200 if hormone-like substances adenosine monophosphate), which, subse- tend to decrease in size in later life (Wal- are included (Bit.ly/PFHormones; Silver quently, initiate the desired effect of the hor- lace and Kelsey, 2004). Ova develop in and Kriegsfeld, 2001). mone in the target cell (Foster et al, 2019). fluid-filled sacs called follicles; as follicles Hormones exert their physiological enlarge, they release oestrogen, the female effects by binding to specific receptors Steroid hormones sex hormone that promotes the thickening associated with their target cells (Fig 3). Steroid hormones are lipids (), mostly

JENNIFER N.R. SMITH JENNIFER of the uterine lining (endometrium). Many drugs have been designed to target derived directly from cholesterol, which

Nursing Times [online] May 2021 / Vol 117 Issue 5 40 www.nursingtimes.net Copyright EMAP Publishing 2021 This article is not for distribution except for journal club use Clinical Practice Systems of life acts as a precursor for steroid enter sites of and begin to trap The endocrine system biosynthesis. Examples include: and kill pathogens, they release a and homoeostasis l Oestrogen; (a signalling chemical that is produced by An average adult human with a weight of l Progesterone; immune cells) called interleukin-1 (IL-1). 70kg is thought to comprise around l Testosterone; IL-1 is a small peptide that circulates in the 30-40 trillion cells (Sender et al, 2016). For l Cortisol. blood before binding to receptors on cells each cell to function effectively, it must be As steroid hormones are lipids, they rap- in the hypothalamus – the region of the maintained at the correct temperature and idly diffuse across the phospholipid bilayer brain containing the thermoregulatory pH, and provided with a steady stream of of their target cell membranes (Fig 3) and centre that is responsible for controlling and . At the same time, exert their effects by binding to receptors in body temperature, which usually has a set the local environment of each cell needs the cytoplasm or nucleus (Ozawa, 2006). point of around 37°C (Knight et al, 2020). any waste metabolites, such as Steroid hormones tend to precipitate their Once IL-1 has binded to its receptor, the dioxide and urea, to be efficiently removed. desired effects by modulating the activity of enzyme cyclooxygenase (COX) is activated, Homoeostasis can be broadly defined as particular genes in cells. leading to the production of the eicosa- the ability to maintain a relatively stable noid, prostaglandin E2 (PGE2); this locally ; it is essential to -derived hormones acting signal shifts the set point of the good health and survival (Modell et al, These are synthesised from amino acids, hypothalamus upwards (typically to 2015). A multitude of variables in the body so are small with low molecular around 38°C-39°C), leading to fever are susceptible to continual and signifi- weights. Examples include: (Eskilsson et al, 2017). cant fluctuation, and most of the major l Adrenaline (epinephrine), derived from organ systems of the body are dedicated to tyrosine; “It has been suggested that keeping these variables within their l Thyroid hormones thyroxine T4 and the microbial biome (the normal physiological ranges. T3, derived from tyrosine; The internal biochemical processes l Melatonin (which helps to regulate diverse micro-organisms necessary for life are primarily driven by sleep), derived from tryptophan (Kleine colonising the body) also biological catalysts known as enzymes, and Rossmanith, 2016). functions as a virtual which generally fall into two categories: Like peptide hormones, some amino endocrine organ” l Anabolic enzymes – these are acid-derived hormones, such as adrena- responsible for building molecules in line, bind to receptors on the surface of the body. For example, DNA target-cell plasma membranes. Others Fever is a useful response during infec- polymerase builds new molecules of however, such as T3 from the thyroid, cross tion as it can slow the replication of patho- DNA necessary for cell division and the plasma membranes of their target cells gens, while simultaneously speeding up growth, while glycogen synthase takes and bind to receptors inside the cell in a and enhancing pathogen killing by leuko- single molecules of glucose and similar manner to steroid hormones. cytes. However, fever also takes enzymes in polymerises them (links them the body cells outside of their normal together) to form long, branching Locally acting hormones: optimal temperature of 37°C, slowing the chains of glycogen (animal starch), autocrine and paracrine biochemical reactions that are necessary which is stored in large amounts in As well as the hormones secreted by the for life. This can cause people to experi- liver and muscle; major endocrine glands, there are various ence malaise and feel generally unwell l Catabolic enzymes – these break locally acting hormone-like substances. until the infection is dealt with and the down molecules and include the These are usually released into the intersti- temperature can return to normal. enzymes of the digestive tract, which tial fluid (the thin film of tissue fluid sur- If fever becomes extremely high digest the macromolecules (large, rounding most cells) and exert their effects (≥40°C), there is an increased risk of febrile complex molecules) of food into in the local vicinity. convulsions. Antipyretic drugs – which simple components that can be Autocoids are chemical signals released include many common non-steroidal absorbed and used by the body. Other by a cell that exert their effects on that anti-inflammatory drugs (NSAIDs), such key catabolic enzymes are those same cell; paracrine signals act more as aspirin – may be given to reduce the involved in cellular respiration, in widely, affecting neighbouring cells in the fever. NSAIDs work, primarily, by inhib- which sugars are metabolised (usually immediate vicinity (Alberts et al, 2015). iting the activity of the enzyme COX, in the presence of oxygen) to release These locally acting hormones – both auto- thereby preventing the production of PGE2 the energy necessary for life. crine and paracrine – are usually rapidly and shifting upwards the set point of the Anabolic and catabolic enzymes can broken down before they can enter the thermoregulatory centre. only function efficiently in narrow ranges wider circulation. Good examples are the If a patient’s fever needs to be reduced, it of temperature and pH; they also require a eicosanoids, a large family of lipid-derived is common practice to combine the use of steady supply of the substrate molecules on molecules, which include the prostaglan- antipyretic drugs and interventions such as which they act (Puri, 2018). As an example, dins, thromboxanes, leukotrienes and reducing bed linen – for example, air-circu- for aerobic cellular metabolism to occur, lipoxins (O’Donnell et al, 2009). lating or -circulating blankets or the respiratory enzymes in cells require a hydrogel-coated water-circulating pads can steady stream of glucose and oxygen. Prostaglandins and the fever response also be used. There is no evidence that fans The homoeostatic mechanisms that Fever (pyrexia) is commonly associated help with temperature regulation and should ensure a stable environment in the body with infection. When phagocytic leuko- be avoided as they can increase the risk of rely on a process called , cytes (white blood cells) such as monocytes shivering (Doyle and Schortgen, 2016). which is discussed below.

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Fig 4. Negative feedback and glucose homoeostasis vital bodily functions. Each of the major endocrine glands and their hormonal Insulin Insulin secretions will be be examined in greater detail later in the series; part 2 focuses on 6mmol/L the hypothalamus and pituitary gland. NT Blood glucose 5mmol/L set point 4mmol/L References Alberts B et al (2015) The Molecular Biology of the Cell. Garland Science. Glucagon Glucagon Glucagon Dorion D (2017) Thyroid Anatomy. reference. medscape.com, 30 November. Doyle JF, Schortgen F (2016) Should we treat pyrexia? And how do we do it? Critical Care; 20, 303. Set points, negative feedback and the released; this stimulates the release of Eskilsson A et al (2017) Immune-induced fever Is dependent on local but not generalized role of hormones stored glucose from the liver, which causes prostaglandin E2 synthesis in the brain. Journal of For each variable in the human body, there blood glucose to rise again. The two pan- Neuroscience; 37: 19, 5035-5044. is a hypothetical ideal value – the set point. creatic hormones, insulin and glucagon, Foster SR et al (2019) Discovery of human signaling systems: pairing peptides to G - As an example, the set point for glucose is work antagonistically to each other to coupled receptors. Cell; 179: 4, 895-908. around 5mmol/L (Fig 4); at 5mmol/L, effectively constrain the blood–glucose Ganapathy MK, Tadi P (2020) Anatomy, Head and human cells are supplied with a steady concentration in its normal physiological , Pituitary Gland. StatPearls. Kleine B, Rossmanith WG (2016) Hormones and supply of glucose, which can be used to range of 4-6mmol/L (Knight et al, 2020). the Endocrine System. Springer. release energy during cellular respiration. Knight J et al (2020) The endocrine system. In: Understanding Anatomy and Physiology in The body strives to maintain variables Effects of variables outside of their Nursing. Sage. as close to their set points as possible using normal range Lack EE, Paal E (2020) Adrenal glands. In: Cheng negative-feedback mechanisms. During One in 14 people in the UK has the chronic L et al (eds) Urologic Surgical . Elsevier. Longnecker DS (2021) Anatomy and of negative feedback, any deviations from the metabolic disease, diabetes mellitus (Bit. the pancreas. The Pancreapedia: Exocrine Pancreas set point are resisted and minimised, ly/DUKStats), which means they no longer Knowledge Base. doi: 10.3998/panc.2021.01. allowing a variable to be constrained produce insulin (type 1) or become Modell H et al (2015) A physiologist’s view of homoeostasis. Advances in Physiology Education; within a narrow, normal physiological resistant to its effects (type 2). Without an 39: 4, 259-266. range. If blood–glucose concentration is effective insulin response, blood–glucose Moser SC, van der Eerden BCJ (2019) Osteocalcin – a versatile bone-derived hormone. Frontiers in measured throughout the day, it would be concentration will rise markedly above its ; 9: 794. expected to fluctuate around its set point. normal physiological range. Some undiag- Mukherjee E et al (2011) Endocrine and metabolic As an example, after , blood–glu- nosed patients with diabetes can have seri- emergencies: hypoglycaemia. Therapeutic Advances in Endocrinology and Metabolism; 2: 2, 81-93. cose concentration typically falls as glu- ously high blood–glucose concentrations O’Callaghan TF et al (2016) The gut microbiome cose is used to provide energy for muscle of >33mmol/L requiring immediate treat- as a virtual endocrine organ with implications for contraction; conversely, after a carbohy- ment (Bit.ly/DiabetesHONK). Elevated farm and domestic animal endocrinology. Domestic Animal Endocrinology; 56: S44-S55. drate-rich meal or snack (such as a choco- blood glucose is called hyperglycaemia O’Donnell VB et al (2009) Eicosanoids: generation late bar), the blood–glucose level rises. and is the key clinical feature of diabetes. and detection in mammalian cells. Methods in Molecular Biology; 462: 5-23. Hormones frequently play major roles Many patients with diabetes inject Ozawa H (2006) Steroid hormones, their in negative feedback and often work insulin to manage and normalise their receptors and neuroendocrine system. Journal of together in antagonistic pairs. Fig 4 shows blood–glucose levels. On occasion, some Nippon ; 72: 6, 316-325. Puri D (2018) Textbook of Medical . that when blood–glucose concentration may inject too much insulin or eat insuffi- Elsevier. rises, the hormone insulin is released; this cient carbohydrate so their blood–glucose Sender R et al (2016) Revised estimates for the promotes glucose uptake by the cells of the concentration falls far below its normal number of human and bacteria cells in the body. PLoS Biology; 14: 8, e1002533. body and the blood–glucose level drops. physiological range; this is called hypogly- Silber S (2018) Fundamentals of Male Infertility. Conversely, if blood–glucose concentra- caemia and can be extremely dangerous. Springer. Silver R, Kriegsfeld LJ (2001) Hormones and tion falls, the hormone glucagon is When pronounced, hypoglycaemia can Behaviour. Wiley Online Library. lead to mental impairment, behavioural Wallace WH, Kelsey TW (2004) Ovarian reserve changes, unconsciousness, coma and and reproductive age may be determined from measurement of ovarian volume by transvaginal Nursing Times potentially death (Mukherjee et al, 2011). sonography. ; 19: 7, 1612-1617. Self-assessment The example of hyperglycaemia and online hypoglycaemia shows how, when a vari- CLINICAL able is taken outside of its normal range SERIES Endocrine system Test your knowledge with Nursing for any protracted length of time, it is det- Part 1: Overview of the endocrine system Times Self-assessment after reading rimental to health and leads to pathology and hormones May this article. If you score 80% or more, (disease states); both hyperglycaemia and Part 2: Hypothalamus and pituitary gland Jun you will receive a personalised hypoglycaemia are frequently encoun- Part 3: Thyroid and parathyroid glands Jul certificate that you can download and tered in poorly managed diabetes. Part 4: Adrenal glands Aug store in your NT Portfolio as CPD or Part 5: Pineal and thymus glands Sep revalidation evidence. Conclusion Part 6: Pancreas, stomach, liver, small This article has provided a general over- intestine Oct To take the test, go to: view of the nature of hormones, along with Part 7: Ovaries and testes, placenta () Nov nursingtimes.net/NTSAEndocrine the major endocrine glands and their Part 8: Kidneys, heart and skin Dec importance in regulating and coordinating

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