Learning

The Hormones : Corticoids
  1. Construction and Production
  2. Revving Up
  3. Glucocorticoids
  4. Mineralocorticoids
  5. Corticoid Disrupters
  6. Research History
  7. References

cortisolCorticoid hormones balance stress response, energy flow, body temperature, water balance, and other essential processes. Two groups, the glucocorticoids and the mineralocorticoids, chemically control some of the most basic actions necessary to protect, nourish, and maintain the body. The gender-neutral corticoids guide these life-sustaining functions in both males and females.

CAPTION: Hydrocortisone, also called cortisol, is a glucocorticoid hormone. (click image for 3-D interactive animation) CREDIT: ChemIDPlus, National Library of Medicine

Construction and Production

Cholesterole to Cortidoid Synthesis DiagramCorticoids are a group of chemically related steroid hormones. Steroids are a special kind of fat molecule with a four-ringed, carbon atom backbone or core, like their cholesterol predecessor. A series of chemical reactions, spurred by proteins called enzymes, remove and add groups to cholesterol's polycyclic (many-ringed) core. These actions transform it first into the steroid pregnenolone, then into 11-deoxycorticosterone or 17-α-hydroxyprogesterone, and finally into the corticoid hormones corticosterone, cortisol, and aldosterone.

The adrenal glands, nestled atop the kidneys, produce glucocorticoids and mineralocorticoids in humans and other mammals. Fish, amphibians, reptiles, and birds make them in a similar organ called the interrenal gland.

CAPTION: Many chemical changes turn cholesterol into corticoid hormones. CREDIT: Tulane/Xavier Center for Bioenvironmental Research.


Revving Up

Corticoid Receptor BindingLike all steroid hormones, glucocorticoids and mineralocorticoids produce effects by docking with receptors on the cell's membrane surface or inside the cell in the liquid cytoplasm. Binding in either location triggers different chemical signaling systems.

A hormone uniting with a surface receptor starts a lightening-fast chemical relay in the cytoplasm that trigger changes in cellular chemistry to initiate hormone release or spark nerve signal transmission. In contrast, when steroid hormones go inside a cell, they can bind with a receptor to form a hormone/receptor unit that moves into the nucleus, attaches directly to special DNA binding sites, and activates protein-producing genes. The proteins made during this process drive the cell changes that coordinate ion and energy balance (Cato et al. 2002).

CAPTION: Corticoid receptor binding. (click image for animation) CREDIT: Tulane/Xavier Center for Bioenvironmental Research.



Glucocorticoids

Glucocorticoids are named for their role in releasing the sugar glucose. But the hormone group's moniker belies their widespread importance. These hormones affect every system of the body and guide fundamental processes associated with converting sugar, fat, and protein stores to useable energy; inhibiting swelling and inflammation; and suppressing immune responses.

Best known is their role in stress relief. Often called the "stress hormones," glucocorticoids fly into action to provide the energy needed for combating physical or emotional stress, including, but not limited to, fever, illness, injury, or safety threats. Their signals to liver, fat, and muscle speed up the chemical breakdown - or metabolism - of stored sugar, fat, and protein.

To generate energy, glucocorticoids signal the liver to both release its own stored glucose and to soak up muscle proteins and fats from the blood and convert them into glucose. Breaking apart this molecular food releases stored energy that is then dumped into the bloodstream as glucose. The glucose is preferentially delivered to the brain and heart to fuel the fight-or-flight responses to the perceived stress.

Hydrocortisone, also called cortisol, corticosterone, 11-deoxycortisol, and cortisone are the types of glucocorticoids found in most vertebrates. Cortisol is the most abundant and potent glucocorticoid in humans and fish. Corticosterone is most potent in amphibians, reptiles, and birds.

Illness or health problems are tied to glucocorticoid imbalances. For instance, too much cortisol can trigger Cushing's syndrome while too little contributes to Addison's disease. Excessive secretion of glucocorticoids is linked to some types of diabetes. Continuous stress elevates glucocorticoids to levels that can impede other steroid hormones and hinder fertility.




Mineralcorticoids

aldosteroneLike the name denotes, mineralocorticoids regulate minerals - inorganic molecules such as sodium, potassium, and hydrogen. Mainly, these hormones balance mineral levels to maintain water balance in and around cells. Acting mostly in the kidney, colon and salivary glands, they direct cells to retain sodium while excreting potassium and hydrogen ions in the urine. When sodium is retained, water is also retained, increasing the total amount of circulating blood and raising blood pressure. Blood pressure sensors in the kidney help to switch mineralocorticoid release on or off so that the right balance is maintained.

CAPTION: The mineralocorticoid hormone aldosterone. (click image for 3-D interactive animation) CREDIT: ChemIDPlus, National Library of Medicine

Aldosterone is the only mineralocorticoid in four-legged vertebrates. Cortisol, although typically classified as a glucocorticoid, regulates mineral balance in fish and juvenile amphibians.

A proper hormone balance is needed for good health. Too much mineralocorticoid activity can lead to sodium/salt retention, swelling, and high blood pressure, all referred to as hypermineralocorticoidism. Too little activity produces low sodium/salt levels, low blood pressure, and low blood volume, known as hypomineralocorticoidism.




Corticoid Disrupters

At present, scientists have not identified compounds in the environment that directly mimic or block glucocorticoid or mineralocorticoid actions. However, exposure to polychlorinated biphenyls (PCBs) is associated with unusually low glucocorticoid levels in polar bears (Oskam et al. 2004), birds (Love et al. 2003), fish (Aluru et al. 2004), and frogs (Glennemeler and Denver 2001), suggesting that PCBs could interfere with energy balance. The heavy metal arsenic, which naturally pollutes water supplies around the world and was widely used as a wood preservative, can interfere with glucocorticoid hormone-receptor complexes and inhibit gene transcription, a mechanism that might explain the metal’s link to cancer (Kaltreider et al. 2001).




Research History

In 1855, Thomas Addison first described the critical role of the adrenal glands when he documented a disease associated with their atrophy (Addison 1855). Patients felt weak, lost weight, craved salt, had low blood sugar, and very low blood pressure. Later experiments showed the adrenal glands had some effect on the amount of salt excreted by the body and on sugar and starch metabolism.

In 1945, the four glucocorticoids with the greatest effect on blood sugar levels were extracted from the adrenal gland and identified as 11-deoxycortisol, corticosterone, cortisone, and cortisol. In 1952, James F. Tait, Sylvia A. Simpson, and colleagues (Tait et al. 1952; Simpson et al. 1952) extracted a steroid that caused sodium retention and by 1954 identified it as the mineralocorticoid aldosterone (Hadley 2000; Simpson 1954).




References

  • Addison T. 1855. On the Constitutional and Local Effects of Disease of the Supra-renal Capsules. London, UK: Samuel Highley.
  • Aluru N, Jorgensen E, Maule A, and Vijayan M. 2004. PCB disruption of the hypothalamus-pituitary-interrenal axis involves brain glucocorticoid receptor downregulation in anadromous Arctic charr. American Journal of Physiology - Regulatory Integrative and Comparative Physiology 287:R787-793.
  • Cato A, Nestl A, and Mink S. 2002. Rapid actions of steroid receptors in cellular signaling pathways. Science's STKE 2002: re9; doi: 10.1126/stke.2002.138.re9; Available: http://stke.sciencemag.org/cgi/content/full/sigtrans%3b2002/138/re9.
  • Glennemeller K and Denver R. 2001. Sublethal effects of chronic exposure to an organochlorine compound on northern leopard frog (Rana pipiens) tadpoles. Environmental Toxicology 16:287-297.
  • Hadley M. 2000. Endocrinology. Upper Saddle River, NJ:Prentice Hall.
  • Kaltreider RC, Davis AM, Lariviere JP, and Hamilton JW. 2001. Arsenic alters the function of the glucocorticoid receptor as a transcription factor. Environmental Health Perspectives 109(March):245-251.
  • Love O, Shutt L, Silfies J, Bortolotti G, Smits J, and Bird D. 2003. Effects of dietary PCB exposure on adrenocortical function in captive American kestrels (Falco sparverius). Ecotoxicology 12:199-208.
  • Oskam I, Ropstad E, Lie E, Derocher A, Wiig O, Dahl E, Larsen S, and Skaare J. 2004. Organochlorines affect the steroid hormone cortisol in the free-ranging polar bears (Ursus maritimus) in Svalbard, Norway. Journal of Toxicology and Environmental Health Part A 67:959-977.
  • Simpson SA, Tait JF, Wettstein A, Neher R, Von Euw J, Schindler O, and Reichstein T. 1954. Konstitution des Aldosterons, des neuen mineralocorticoids (Constitution of aldosterone, a new mineralocorticoid). Experientia 10(3):132-133.
  • Simpson SA, Tait JF and, Bush IE. 1952. Secretion of a salt-retaining hormone by the mammalian adrenal cortex. Lancet 2(5):226-228.
  • Tait JF, Simpson SA, and Grundy HM. 1952. The effect of adrenal extract on mineral metabolism. Lancet 1(3):122-124.