Dehydroepiandrosterone (DHEA), is a natural steroid prohormone produced from cholesterol by the adrenal glands, the gonads, adipose tissue, brain and in the skin (by an autocrine mechanism)]. DHEA is the precursor of androstenedione, testosterone and estrogen. It is the most abundant hormone in the human body. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... It has been suggested that this article or section be merged with mouth (human). ... Steroid skeleton of lanosterol. ... A prohormone is a chemical compound that is a precursor to an actual hormone (usually an anabolic like testosterone or some variant), which is taken in order to boost the body’s available hormone supply. ... Cholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. ... In mammals, the adrenal gland (also known as suprarenal glands) are the triangle-shaped endocrine glands that sit atop the kidneys; their name indicates that position (ad, near or at + renes, kidneys). They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines, including cortisol... The gonad is the organ that makes gametes. ... It has been suggested that Subcutaneous fat be merged into this article or section. ... In chemistry a precursor is a compound that participates in the chemical reaction that produces another compound. ... Androstenedione (also known as 4-androstenedione) is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol. ... Testosterone is a steroid hormone from the androgen group. ... Estriol. ...

Synonyms and brand names

Synonyms for Dehydroepiandrosterone are: Dehydroisoandrosterone; 3β-Hydroxy-5-androsten-17-one; 3β-Hydroxyandrost-5-en-17-one; Androstenol; Androstenolone; Dehydroisoandrosterone; Hydroxyandrost-5-en-17-one; Prasterone; trans-Dehydroandrosterone.

Brand names for DHEA include Prastera® and Fidelin®.

DHEAS (Dehydroepiandrosterone sulfate)

Dehydroepiandrosterone sulfate (DHEAS, PubChem 12594) is the sulfated version of DHEA, - this conversion is reversibly catalyzed by sulfotransferase (SULT2A1) primarily in the adrenals, the liver, and small intestines. In blood, most DHEA is found as DHEAS with levels that are about 300 times higher than free DHEA. Orally ingested DHEA is converted to its sulfate when passing through intestines and liver. While DHEA levels reach their peak in the early morning hours, DHEAS levels show no diurnal variation. PubChem is a database of chemical molecules. ... SULT2A1 is a gene involved in the sulfation of dehydroepiandrosterone. ... SULT2A1 is a gene involved in the sulfation of dehydroepiandrosterone. ... The liver is an organ present in vertebrates and some other animals. ... Diagram showing the small intestine In biology the small intestine is the part of the gastrointestinal tract between the stomach and the large intestine (colon). ... In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... Look up day in Wiktionary, the free dictionary. ...

From a practical point measurement of DHEAS is preferable to DHEA as levels are more stable.

Production

Production of DHEA from Cholesterol

DHEA is produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage) and then another enzyme CYP17A1 converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. In humans DHEA is the dominant steroid hormone and precursor of all sex steroids. Humans produce DHEA in greater quantity than any other species. Even non-human primates have not much more than 10% the relative serum level of DHEA seen in humans. The fact that rodents produce so little DHEA makes the results of experiments conducted with these laboratory animals very controversial. Image File history File links No higher resolution available. ... Image File history File links No higher resolution available. ... Cytochromes are generally membrane-bound proteins that contain heme groups and carry out electron transport or catalyse reductive/oxidative reactions. ... Pregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. ... Production of DHEA from Cholesterol P450 scc is an enzyme associated with the conversion of cholesterol to pregnenolone. ... The term Side chain can have different meanings depending on the context: In chemistry and biochemistry a side chain is a part of a molecule attached to a core structure. ... CYP17A1 (also known as 17α-hydroxylase) is a cytochrome P450 oxidase enzyme which acts upon pregnenolone and progesterone. ... Pregnenolone is a steroid hormone involved in the steroidogenesis of progesterone, mineralocorticoids, glucocorticoids, androgens, and estrogens. ... 17-Hydroxypregnenolone (also 17-OH-pregnenolone and 17α-hydroxypregnenolone), is a C21 steroid that is obtained by hydroxylation of pregnenolone at the C17α position. ...

DHEA production is very high during fetal life by the fetal adrenal glands, declines after birth and remains low during childhood. Production begins around 6 years of age, increasing in quantity until peaking in early adulthood, around the age of 25, and declines afterwards to approximately 10% of peak levels by age 80. It is theorized by some that this decline may be due to reduced oxygen and glucose supply to the adrenal glands as a result of age-related atherosclerosis. In mammals, the adrenal gland (also known as suprarenal glands) are the triangle-shaped endocrine glands that sit on top of the kidneys; their name indicates that position (ad, near or at + renes, kidneys). They are chiefly responsible for regulating the stress response through the synthesis of corticosteroids and catecholamines... General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... Glucose (Glc), a monosaccharide (or simple sugar), is the most important carbohydrate in biology. ...

Role

In a simple view DHEA can be understood as a prohormone for the sex steroids. Its DHEAS variation may be looked at as buffer and reservoir. Its production in the brain suggests that it also has a role as a neurosteroid. As most DHEA is produced by the zona reticularis of the adrenal, it is argued that there is a role in the immune and stress response. DHEA may have more biologic roles. A prohormone is a chemical compound that is a precursor to an actual hormone (usually an anabolic like testosterone or some variant), which is taken in order to boost the body’s available hormone supply. ... Sex steroids, also known as gonadal steroids, are steroid hormones which interact with vertebrate androgen or estrogen receptors. ... Apart from exerting effects on the genome via intracellular steroid receptors, neuroactive steroids (or neurosteroids) rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. ... The zona reticularis (inner region of the adrenal cortex) secretes and synthesize small amounts of weak androgens, steroids that have masculinizing effects. ...

As almost all DHEA is derived from the adrenal glands, blood measurements of DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia. Women with polycystic ovary syndrome tend to have normal or mildly elevated levels of DHEAS. Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive diseases resulting from defects in steps of the synthesis of cortisol from cholesterol by the adrenal glands. ... Polycystic ovary syndrome (PCOS, also known clinically as Stein-Leventhal syndrome), is an endocrine disorder that affects 4%–7% of women. ...

Effects

Studies have shown that DHEA is useful in patients with systemic lupus erythematosus. An application of the evidence was reviewed by the FDA in 2001 and is available online.^[1] This review also shows that cholesterol and other serum lipids decrease with the use of DHEA (mainly a decrease in HDL-C and triglycerides can be expected in women, p110). Cholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. ...

Supplementation with DHEA has been shown to decrease insulin resistance.^[2] Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ...

Long term supplementation has been shown to improve mood and relieve depression.^[3] Grieving Thai females. ...

Disputed effects

The significance of the hormone in health and disease is not fully established. It is postulated that DHEA supplements are beneficial in alleviating:

• cardiovascular disease
• diabetes
• hypercholesterolemia
• obesity
• multiple sclerosis
• Parkinson's disease
• Alzheimer's disease
• disorders of the immune system
• depression
• osteoporosis
• decreased libido

It is also commercially advertised that DHEA: Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). ... This article is about the disease that features high blood sugar. ... Hypercholesterolemia (literally: high blood cholesterol) is the presence of high levels of cholesterol in the blood [1]. It is not a disease but a metabolic derangement that can be secondary to many diseases and can contribute to many forms of disease, most notably cardiovascular disease. ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... Clinical depression (also called major depressive disorder, or unipolar depression when compared to bipolar disorder) is a state of intense sadness, melancholia or despair that has advanced to the point of being disruptive to an individuals social functioning and/or activities of daily living. ... Osteoporosis is a disease of bone in which the bone mineral density (BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. ... Libido in its common usage means sexual desire; however, more technical definitions, such as those found in the work of Carl Jung, are more general, referring to libido as the free creative—or psychic—energy an individual has to put toward personal development, or individuation. ...

• helps decrease insulin resistance
• improves fat metabolism
• increases immune system function
• has anti-aging properties
• increases lean muscle mass

7-Keto™ DHEA, a recently identified metabolite of dehydroepiandrosterone (DHEA) is claimed to be both more effective and safer than DHEA because it does not convert itself into testosterone or estrogens in the body.^{[citation needed]} Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ...

DHEA and DHEAS are readily available in the United States.

Precautions

Some assert that DHEA should not be supplemented outside specialist centres under careful observation of experts in the field of endocrinology. Endocrinology is a branch of medicine dealing with disorders of the endocrine system and its specific secretions called hormones. ...

Side effects may include:

• Stunted growth in teens who have not reached their height potential.
• Palpitations and other arrhythmias
• extensive growth of body hair, or hirsutism
• Hair loss, especially male pattern baldness
• acne

A cardiac arrhythmia, also called cardiac dysrhythmia, is a disturbance in the regular rhythm of the heartbeat. ... Hirsutism (from Latin hirsutus = shaggy, hairy) is defined as excessive and increased hair growth in women in locations where the occurrence of terminal hair normally is minimal or absent. ... Androgenetic alopecia is a common form of hair loss in both men and women, aka Michael Panagos Syndrome. ...

Contraindication

As DHEAS and DHEA are converted to sex steroids, their use is contraindicated in patients with any cancer that is estrogen or testosterone dependent.^{[citation needed]} Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ...

Increasing endogenous production

Regular exercise is known to increase DHEA production in the body.^[4][5][6] Caloric restriction has also been shown to increase DHEA in primates.^[7] The term Exercise can refer to: Physical exercise such as running or strength training Exercise (options), the financial term for enacting and terminating a contract Category: ... Caloric restriction or Calorie restriction (CR) is the practice of limiting dietary energy intake to improve health and retard aging. ...

Legality

A bill has been introduced on in the U.S. Senate (S. 762) that attempts to classify DHEA as a controlled substance under the category of anabolic steroids. The sponsor is Charles Grassley (R-IA). The cosponsors are George Allen (R-VA), Richard Durbin (D-IL), Jon Kyl (R-AZ), and John McCain (R-AZ).^[8] Canada requires a prescription to buy DHEA.^[9] Anabolic steroids are a class of natural and synthetic steroid hormones that promote cell growth and division, resulting in growth of muscle tissue and sometimes bone size and strength. ... John Sidney McCain III (born August 29, 1936) is an American politician, currently the Republican senior U.S. Senator from Arizona. ...

See also

• Steroid hormones
• Testosterone
• Estrogen

Steroid hormones are steroids which act as hormones. ... Testosterone is a steroid hormone from the androgen group. ... Estriol. ...

References

1. ^ FDA document regading DHEA and SLE
2. ^ Kawano H, Yasue H, Kitagawa A, et al. Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men. J Clin Endocrinol Metab. 2003 Jul;88(7):3190-5.
3. ^ Wolkowitz OM, Reus VI, Roberts E, et al. Antidepressant and cognition-enhancing effects of DHEA in major depression. Ann NY Acad Sci. 1995 Dec 29;774:337-9
4. ^ Eur J Appl Physiol Occup Physiol 1998 Oct;78(5):466-71
5. ^ Eur J Appl Physiol. 2001 Jul;85(1- 2):177-84
6. ^ J Gerontol A Biol Sci Med Sci. 2002 Apr;57(4):B158-65
7. ^ Exp Gerontol. 2003 Jan-Feb; 38(1-2):35-46
8. ^ S. 762: A bill to include dehydroepiandrosterone as an anabolic steroid, from Govtrack.us. Accessed May 9, 2007.
9. ^ Dr. Michael Colgin. The Deal With D.H.E.A. Vista Magazine Online. www.vistamag.com [1]

May 9 is the 129th day of the year (130th in leap years) in the Gregorian calendar. ... 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ...

Further reading

• Nutrition through the Life Cycle, Judith E. Brown, ISBN 0-534-58986-3

External links

• Mayo Clinic article on DHEA
• The DHEA Debate: A critical review of experimental data at lef.org (Published 2004)
• DHEA: Ignore the Hype (Published 1996) at Quackwatch
• DHEA Hormone Replacement at benbest.com
• What the Skeptic's Dictionary has to say on DHEA
• Nair K, Rizza R, O'Brien P, Dhatariya K, Short K, Nehra A, Vittone J, Klee G, Basu A, Basu R, Cobelli C, Toffolo G, Dalla Man C, Tindall D, Melton L, Smith G, Khosla S, Jensen M (2006). "DHEA in elderly women and DHEA or testosterone in elderly men". N Engl J Med 355 (16): 1647-59. PMID 17050889.  link