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Dehydroepiandrosterone
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DHEA
Full name:dehydroepiandrosterone
Synonyms:3ß-hydroxy-5-androsten-17-one
Empirical formula: C 19 H 28 O 2
Molecular weight:288.43
CAS No53-43-0
Melting point ( K )419 to 424 K
Melting point ( °C )146 to 151 °C



Dehydroepiandrosterone ('''DHEA''') is a natural Steroid Hormone produced from Cholesterol by the Adrenal Gland s found atop of the Kidney s in the Human Body .
DHEA is also produced in the Gonad s, Adipose Tissue and the Brain . DHEA is structurally similar to, and is a precursor of, Androstenedione , Testosterone and Estrogen . It is the most abundant hormone in the human body.


DHEA-DHEAS

Dehydroepiandrosterone sulfate ('''DHEAS''') 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. DHEAS is biologically active only after its sulfate group has been split and it becomes DHEA again.

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


PRODUCTION


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 P450c17 (CYP17A) 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.

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 .


ROLE OF DHEA

In a simple view DHEA can be understood as a Prohormone for the Sex Steroid s. Its DHEAS variation may be looked at as buffer and reservoir. Its production in the brain suggests that is 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.

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.


DISPUTED EFFECTS OF DHEA


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

It is also commercially advertised that DHEA:
  • helps decrease Insulin Resistance

  • improves fat metabolism

  • increases immune system function

  • has anti-aging properties

  • increases lean muscle mass


DHEA and DHEAS are readily available in the United States, but not in many other countries.


EFFECTS OF DHEA

  • Supplementation with DHEA has been shown to decrease Insulin Resistance . ''(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.)''

  • Long term supplementation has been shown to improve mood and relieve depression. ''(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)''



PRECAUTIONS


Some assert that DHEA should not be supplemented outside specialist centres under careful observation of experts in the field of Endocrinology .

Side effects may include:
  • extensive growth of body hair, or Hirsutism

  • male pattern baldness

  • acne



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.


INCREASING ENDOGENOUS DHEA PRODUCTION


Regular exercise is known to increase the amount of DHEA in the body. ''(Eur J Appl Physiol Occup Physiol 1998 Oct;78(5):466-71), (Eur J Appl Physiol. 2001 Jul;85(1- 2):177-84), (J Gerontol A Biol Sci Med Sci. 2002 Apr;57(4):B158-65).'' Caloric Restriction has also been shown to increase DHEA in primates ''(Exp Gerontol. 2003 Jan-Feb; 38(1-2):35-46).''


METABOLITES

DHEA is converted to approximately 150 metabolites in the human body. One of these is 3-acetyl-7-oxo-dehydroepiandrosterone. Studies have shown that this metabolite appears to be responsible for some of the beneficial results that have been attributed to DHEA. This substance does not raise testosterone or estrogen levels. As a consequence, some individuals who do not wish to elevate their levels of sex hormones ingest this metabolite in pill form.


SEE ALSO

Steroid Hormone


FURTHER READING

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


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