ESTROGENS and ESTROGENIC EXPOSURE
The following document was prepared for a nutrition course I was taking. My project
was given orally so some of the text is in point form. The text was originally prepared
in Tex and may contain some remnants of Tex formatting. Any factual errors contained in
this document are ones that I have made interpreting the available literature.
Scientists don't always agree and all divergent opinions may not have been available.
Many ideas are not included here due to lack of space (I was limited to about 10 pages).
This is currently a topic of considerable scientific interest. Hopefully, this document
will stimulate some of you to investigate some areas more thoroughly. The document was
prepared over several months in the spring of 1994. - Ron Lyons
Please email comments, corrections, or criticisms to
Ron Lyons. I still find this topic very interesting.
While the literature is extensive and our awareness of the problem
is growing in leaps and bounds the total ramifications of estrogens in the
environment are unknown. Perhaps the reason it hasn't had a higher
profile in the news media is because we have been saturated with
bad news about the environment. So why should we regard this problem
any differently? Just as the first picture of the Earth from space
heightened our awareness that the Earth was not an infinite source
or sink, and economic factors have forced a recognition of the global
nature of the economy, so the problem of environmental estrogens
may force us to acknowledge the global nature of the environment and the
impact every industry, every activity and every person has on it.
In 1939 Buxton and Engle in talking about the clinical use of estrogens
warned that estrogens are `` not innocuous substances but act on various
organs and functions of the body not intimately related to the gonads......
The observed effects in women and the abundance of data on progressive
effects in animals should raise a reasonable doubt in the mind of the
clinician that these substances may be given with impunity''(quote from
Edelman (1986)). For example, Grossman (1984) pointed out that the sex
hormones regulate and were regulated by the immune system and the degree of
their interactions is far more complex than ever realized. The variety
of estrogenic compounds and their widespread distribution in the environment
prompted Field et al (1990) to point out that we now live in a ``sea of
Perhaps the first alarm based on real life experience was sounded
around 1970 when reproductive problems in avain populations were related to
DDT. While useage stopped shortly thereafter in North America, useage
still contiues in other areas of the world. DDT was found to have
estrogenic properties as well as some of its metabolites. Since its introduction
in the early 1940's, many other chemicals have been introduced into
the environment. While many problems in wildlife populations
are related to loss/degradation of habitat, a number of reproductive and
behavior problems in shellfish, fish, bird, turtle and mammal populations
are gaining widespread attention.
(Surprisingly, no mention was made about the worldwide
decline in the frog and toad populations that made the news last year.
Perhaps this was an oversight in the articles I read.)
Increasingly, attention is being focussed
on the prevalence of estrogenic compounds in the environment and hence
the food chain.
Recently (Sharpe & Skakkebaek, 1993), environmental estrogens were suggested
as a possible cause of falling sperm counts and rising levels
of male reproductive tract problems being reported worldwide. Estrogens
in the environment have been the subject of several conferences, the most
recent in January of this year (Raloff 1994).
The problems related to the study of estrogen in the environment
and its impact on the life forms in that environment are difficult
and require input from many areas and in some cases many years of
detailed work. Advances in science and technology may force the entire
effort to be set aside if the avenues of exploration or data-taking
have not been broad enough. A coordinated cross-disciplinary approach
will be necessary.
estrogen - generic term for estrus producing steroid compounds
-- -- female sex hormones.
-- -- formed in the ovary, possibly the adrenal cortex, the testes and the
-- -- various functions in both sexes.
estrogenic - producing estrus; having properties of or similar to an estrogen
- Hertz's definition (quoted by Soto et al 1991)
-- -- primary effect of an estrogen is stimulation of mitotic activity in female
-- -- a substance which can directly elicit this response is an estrogen
-- -- a substance which cannot elicit this response is not an estrogen
-- -- (question: are there any substances that do in animals but not humans?)
3. ENDOGENOUS ESTROGENS
estradiol - most potent naturally occuring ovarian and placental estrogen in
humans. The most active of the two isomers is estradiol-17.
estradiol ethinyl - orally effective semi-synthetic derivatie of estradiol.
estradiol fatty acid esters - fully potent metabolite of estradiol (Hochberg et al 1990)
estriol - reduction product of estradiol and estrone
estrone - oxidation product of estradiol
4. ESTABLISHING ESTROGENICITY
Normal operation of estrogen in the body.
All classes of biologically active steroids are lipids. Their major metabolites,
the conjugates are highly polar and usually charged. This renders the steroid
water soluble so that it can be excreted easily. The fatty acid esters are
somewhat different in that they are lipophilic. There is an indication that the
estradiol metabolism pathway shifts in aging women from estrone which is less
active and can be cleared easily to LE