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Estrogen

References

Estradiol, the molecule pictured here, is the most abundant and potent estrogen hormone. Estrone and estriol are other types of estrogens. The red balls represent OH or hydroxy groups that extend off the carbon (blue balls) based ring structures, referred to as "polycyclic" because they consist of several rings (cycles) attached together.

Estrogen's actions were initially described by Stockard and Papanicolaou in 1917 with guinea pigs (1) and by Long and Evans in 1922 using rats (2). Both observed that pre-ovulatory follicle swelling was followed by uterine lining growth and vaginal cell maturation.

Later, Allen and Doisy isolated the responsible steroid, called it estrone and described a test to detect this estrogenic activity in biological samples (3). Since then, their test, or similar ones, has become the standard way to detect, identify and characterize natural and synthetic compounds with estrogenic activity (4).

Estrogen is commonly defined as "any of a family of steroid hormones that regulate and sustain female sexual development and reproductive function" (5). In this same vein, modern scientists define estrogens as materials that stimulate tissue growth by (6):

• promoting cell proliferation (DNA synthesis and cell division) in female sex organs (breasts, uterus),
• promoting hypertrophy, or increasing a cell's size, such as occurs in female breast and male muscle during puberty and
• initiating synthesis (making) of specific proteins.

Under these guidelines, any natural steroids, plant compounds or synthetic chemicals that elicit these responses in laboratory tests are considered to be estrogenic. All are not satisfied with this interpretation, however. In a recent comment, Lieberman suggests that classifying a variety of compounds as estrogens is too broad and causes confusion (4).

In a response, Hughes offers to define estrogens as compounds that produce the behavior estrus ("the portion or phase of the sexual cycle of female animals characterized by willingness to accept the male"). He argues that since only true steroid compounds produce estrus, the plant and synthetic compounds that mimic other estrogenic responses are not estrogens and should be classified as something else, such as phytochemicals or environmental estrogens. In his view, "the potential importance of phytoestrogens in human health and disease is certain to derive both from their mimicry of steroidal estrogens and their failure to closely mimic the actions of steroidal estrogens." (7)

1. Stockard, C.R. and G.N. Papanicolaou. 1917. Am. J. Anat. 22:225.

2. Long, J.A. and H.M. Evans. 1922. The Oestrous cycle in the rat and its associated phenomena. Mem. Univ. Calif. 6:1.

3. Allen, E. and Doisy, A.E. 1923. An ovarian hormone: preliminary report on its localization, extraction and partial purification and actions in test animals. JAMA 81: 819.

4. Lieberman, S. 1996. Are the differences between estradiol and other estrogens, naturally occurring or synthetic merely semantical? Journal of Clinical Endocrinology and Metabolism 81(2):850-851.

5. Dictionary of Science and Technology. 1992. San Diego:Academic Press, Inc.

6. Hertz, R. 1985. The estrogen problem: retrospect and prospect. In: Estrogen in the Environment II: Influences on Development (p 1-11). Ed. J. A. McLachlan. New York: Elsevier.

7. Hughes, C. 1996. Are the differences between estradiol and other estrogens merely semantical? (Letter to the Editor). Journal of Clinical Endocrinology and Metabolism 81(6):2405.

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