human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

s and other

animal Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...

s, the adrenocortical hormones are

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...

s produced by the

adrenal cortex The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is ...

, the outer region of the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...

. These polycyclic steroid hormones have a variety of roles that are crucial for the body’s response to stress (for example, the

fight-or-flight response The fight-or-flight or the fight-flight-or-freeze response (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first des ...

), and they also regulate other functions in the body. Threats to

homeostasis In biology, homeostasis (British English, British also homoeostasis) Help:IPA/English, (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physics, physical, and chemistry, chemical conditions maintained by organism, living systems. Thi ...

, such as

injury An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, o ...

, chemical imbalances,

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...

, or

psychological stress In psychology, stress is a feeling of emotional strain and pressure. Stress is a type of psychological pain. Small amounts of stress may be beneficial, as it can improve athletic performance, motivation and reaction to the environment. Exces ...

, can initiate a stress response. Examples of adrenocortical hormones that are involved in the stress response are

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...

and

cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...

. These hormones also function in regulating the

conservation of water Conservation is the preservation or efficient use of resources, or the conservation of various quantities under physical laws. Conservation may also refer to: Environment and natural resources * Nature conservation, the protection and manageme ...

by the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

s and

glucose metabolism Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms. Carbohydrates are central to many essential metabolic pathways. Plants ...

, respectively.Genest, J., Biron, P., Koiw, E., Nowaczynski, W., Chretien, M., & Boucher, R. (1961). Adrenocortical hormones in human hypertension and their relation to angiotensin. Circulation Research, 9, 775-791.

Classes

Adrenocortical hormones are divided into three classes by function: mineralocorticoids, glucocorticoids, and androgens. #

Mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary mi ...

hormones are synthesized in the outermost layer of the

known as the

zona glomerulosa The ''zona glomerulosa'' (sometimes, glomerular zone) of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the renal capsule. Its cells are ovoid and arranged in clusters or arches (''glomus'' is Latin ...

.Shier, D., Butler, J., Lewis, R. “Adrenal Glands.” Hole’s Human Anatomy & Physiology. 12th ed. New York: McGraw-Hill, 2010. 504-508. Their function is to regulate the concentration of electrolytes circulating in the blood. For example,

functions to raise blood sodium levels and lower blood potassium levels by targeting the kidneys. Specifically, it binds receptors of cells that comprise the distal tubules of the kidneys which then stimulate

ion channels Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

to conserve sodium and excrete potassium. onnell, J. M. C., & Davies, E. (2005). The new biology of aldosterone. Journal of Endocrinology, 186, 1-20./ref> Additionally, the ion gradient initiates conservation of water. # The

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

family of hormones is synthesized in the middle layer of the

known as the zona fasciculata. These hormones regulate the processing of proteins, fats, and carbohydrates by the human body. They also play a role in maintaining a normal stress response cycle. # Androgens, or

sex hormones Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects are ...

, are synthesized in the innermost layer of the

known as the

zona reticularis The zona reticularis (sometimes, reticulate zone) is the innermost layer of the adrenal cortex, lying deep to the zona fasciculata and superficial to the adrenal medulla. The cells are arranged cords that project in different directions giving a n ...

. These hormones, such as

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

in females and

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

in males, are commonly known for promoting sexual characteristics and the maturation of reproductive organs of the respective gender.

Structure

Adrenocortical hormones are considered steroid hormones because of the shared characteristic of a

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

backbone. The structures of different steroids differ by the types and locations of additional atoms on a

backbone.Nelson, D. L., Lehninger, A. L., and Cox, M. M. “Hormones are Chemically Diverse.” Lehninger Principles of Biochemistry. 6th ed. New York: W.H. Freeman, 2013. 908. The

backbone consists of four

hydrocarbon In organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons are examples of group 14 hydrides. Hydrocarbons are generally colourless and hydrophobic, and their odors are usually weak or ex ...

rings, three

cyclohexane Cyclohexane is a cycloalkane with the molecular formula . Cyclohexane is non-polar. Cyclohexane is a colorless, flammable liquid with a distinctive detergent-like odor, reminiscent of cleaning products (in which it is sometimes used). Cyclohexan ...

rings and one

cyclopentane Cyclopentane (also called C pentane) is a highly flammable alicyclic hydrocarbon with chemical formula C5H10 and CAS number 287-92-3, consisting of a ring of five carbon atoms each bonded with two hydrogen atoms above and below the plane. It occur ...

, that contribute to its insolubility in aqueous environments. However, the

hydrophobic In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, th ...

nature allows them to readily diffuse through the

plasma membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (t ...

of cells. This is important to the function of steroid hormones as they rely on cellular response pathways to restore the

homeostatic In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and i ...

imbalance that initiated the hormone release.

Synthesis

The synthesis of adrenocortical steroid hormones involves a chain of

oxidation-reduction Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

reactions catalyzed by a series of enzymes. Synthesis begins with a molecule of

. Through shared intermediates and pathways branching off those shared intermediates, the different classes of steroids are synthesized. Steroids are synthesized from

in their respective regions of the

. The process is controlled by

steroidogenic acute regulatory protein The steroidogenic acute regulatory protein, commonly referred to as StAR (STARD1), is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones. It is p ...

(StAR) which sits in the

mitochondrial A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...

membrane and regulates the passage of

. This is the rate-limiting step of

steroid biosynthesis A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

. Once StAR has transported

into the

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

, the

molecule undergoes a string of

reactions catalyzed by a series of enzymes from the family of

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

enzymes. A

coenzyme A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...

system called

adrenodoxin reductase Adrenodoxin reductase (Enzyme Nomenclature name: adrenodoxin-NADP+ reductase, EC 1.18.1.6), was first isolated from bovine adrenal cortex where it functions as the first enzyme in the mitochondrial P450 systems that catalyze essential steps in s ...

transfers electrons to the P450 enzyme which initiates the

reactions that transform

into the steroid hormones.Sushko, T. A., Gilep, A. A., & Usanov, S. A. (2012) Mechanism of intermolecular interactions of microsomal cytochrome P450s CYP17 and CYP21 involved in steroid hormone biosynthesis. Biochemistry, 77(6), 585-592. Though synthesis is initiated inside

, precursors are shuttled to the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

for processing by enzymes present in the

. The precursors are shuttled back to the

in the region of the

within which synthesis initially began and it is there that synthesis is completed.Duarte, A., Poderoso, C., Cooke, M., Soria, G., Cornejo Maciel, F., et al. (2012). Mitochondrial fusion is essential for steroid biosynthesis. PLoS ONE, 7(9): e45829.

Pathology

Cushing's Syndrome

Cushing’s syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...

arises from the repeated

hypersecretion 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...

of glucocorticoids. It can be caused by either an adrenal tumor or by

of adrenocorticotropic hormone (ACTH) from the

anterior pituitary gland A major organ of the endocrine system, the anterior pituitary (also called the adenohypophysis or pars anterior) is the glandular, anterior lobe that together with the posterior lobe (posterior pituitary, or the neurohypophysis) makes up the pi ...

. It is predominantly due to an excess of the

. Secretion is typically regulated by the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

which secretes

corticotropin-releasing hormone Corticotropin-releasing hormone (CRH) (also known as corticotropin-releasing factor (CRF) or corticoliberin; corticotropin may also be spelled corticotrophin) is a peptide hormone involved in stress (biology), stress responses. It is a releasing ...

(CRH) to the

pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...

, stimulating the pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH then travels to the

adrenal glands The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...

and induces the release of

into the bloodstream.Porterfield, J. R., Thompson, G. B., Young, W. F., et al. (2008). Surgery for cushing’s syndrome: An historical review and recent ten-year experience. World J. Surg., 32, 659-677. In

, this process occurs in excess. Some symptoms of an individual with

include low tissue protein levels, due to muscle and bone atrophy, and high blood glucose levels. Sodium levels also see an increase which results in fluid retention in tissues and elevated blood pressure. In addition to

, excess androgens are secreted.Low, G., & Sahi, K. (2012). Clinical and imaging overview of functional adrenal neoplasms. International Journal of Urology, 19, 697-708. In females, increased secretion of androgens, such as

, results in

masculinization Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens. Virilization is most commonly used in three medical and biology ...

which may present as facial hair growth and a deepened voice. Treatment for

aims to reduce the high levels of

circulating through the human body. The course of action ultimately depends on the cause of the

. Cushing’s can be induced by repeated synthetic steroid use to treat

inflammatory diseases Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...

, or it can also be caused by a tumor in the

. In either case, treatment may rely on removal of the tumor or of the

. Without the

, the human body is unable to supply the hormones it produces and therefore requires hormone replacement therapy.

Addison's Disease

Addison’s disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...

is an autoimmune disorder that affects the

such that it is unable to efficiently secrete hormones. The immune system specifically targets the cells of the

and destroys them, but

can also be caused by a severe infection such as

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

. Some symptoms include

hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

and decreased blood sodium levels and increased blood potassium levels caused by a deficiency of

. These electrolyte imbalances induce nerve and muscle issues. Other symptoms include fatigue, salt cravings, weight loss, and increased skin pigmentation. Increased skin pigmentation is caused by a deficiency of the adrenocortical hormone hydrocortisone. Its normal behavior would be as

negative feedback Negative feedback (or balancing feedback) occurs when some function (Mathematics), function of the output of a system, process, or mechanism is feedback, fed back in a manner that tends to reduce the fluctuations in the output, whether caused by ...

at the

, stimulating the

to decrease secretion of

corticotropin Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a Peptide, polypeptide tropic hormone produced by and secreted by the Anterior pituitary, anterior pituitary gland. It is also used as a Adrenocorticotropic hormone ...

. Because hydrocortisone is not able to be produced in

, the

continues to secrete

which binds to the receptor for

melanocyte-stimulating hormone The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating h ...

. It then causes

melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...

to produce more pigment, thus darkening the skin tone.Winqvist, O., Rorsman, F., & Kampe, O. (2000). Autoimmune adrenal insufficiency. BioDrugs, 13(2), 107-114. The standard treatment for

is hormone replacement therapy for the mineralocorticoids and glucocorticoids that are no longer able to be synthesized. 2Former U.S. President

John F. Kennedy John Fitzgerald Kennedy (May 29, 1917 – November 22, 1963), often referred to by his initials JFK and the nickname Jack, was an American politician who served as the 35th president of the United States from 1961 until his assassination i ...

is a well-known individual who suffered from

throughout his presidency. Due to the availability of hormone replacement therapy, he and his staff were able to cover up his condition.

Stress and immunity

Recent studies have discovered a pathway that links stress to the onset of disease through the activation of certain genes.Cole, J.T., Mitala, C. M., Kundu, S., Verma, A., Elkind, J.A., Nissim, I., & Cohen, A.S. (2010). Dietary branched chain amino acids ameliorate injury-induced cognitive impairment. Proceedings of the National Academy of Sciences, 107, 366-371. The experience of psychological stress activates transcription factors that activate genes. In a study by Cole et al., it was concluded that GABA-1 transcription factor activates the interleukin-6-gene. This gene codes for a protein that activates the inflammatory response which directs an

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

to the site of the inflammation.

Chronic inflammation Chronic systemic inflammation (SI) is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions s ...

makes an individual more susceptible to diseases such as

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

heart disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

, and

diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

. Another study found that physical stress caused increased

DHEAS Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroep ...

(dehydroepiandrosterone sulphate) molar ratios which may contribute to reduced immunity, especially in the elderly for whom

ratios are already increased. This is because

levels decrease with age while

levels do not. This high ratio was found to suppress the activity of

neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

and raise susceptibility for

.Butcher, S. K., Killampalli, V., Lascelles, D., Wang, K., Alpar, E. K., & Lord, J. M. (2005). Raised cortisol:DHEAS ratios in the elderly after injury: potential impact upon neutrophil function and immunity. Aging Cell, 4, 319-324.

References

{{Authority control Hormones