PAIS

Partial Gonadal Dysgenesis

"PAIS also affects 46,XY individuals. PAIS patients are born with ambiguous external genitalia due to their partial inability to respond to androgens. "Note: Once again testosterone is an androgen.

"Partial Gonadal Dysgenesis also affects 46,XY individuals, and this condition is characterized by partial testes determination usually accompanied by ambiguous external genitalia at birth. Affected patients may have a combination of Wolffian and Mullerian duct development. The combination of both Wolffian and Mullerian duct development, along with ambiguity of the external structures, indicates that the testes produced more androgens and MIS than those of Complete Gonadal Dysgenesis patients, but not as much as would be seen in normal male development."

Now look at what DES does at the cellular level and to testosterone levels.

In studies done on the rat prostate low doses of DES enhance androgen receptor binding but high doses inhibit androgen receptor binding 16).
"At high dosage, on the other hand, DES produced an opposite effect, inducing hypospadius and inhibiting prostate growth and AR binding activity."
 
DES lowers the over all testosterone levels 27): "DES inhibits luteinizing hormone secretion by the pituitary, there by inhibiting testosterone secretion." Which is why it was used in the treatment of prostate cancer.

The presence of testosterone directly affects androgen receptors 167):
"In analogy with animal studies showing strong activational effects of androgens on nuclear AR-ir, the present data suggest that nuclear AR-ir in the human MBC is dependent on the presence or absence of circulating levels of androgen."

Also see 150):
"The induction of major abnormalities in rats treated with DES (10 µg) was coincident with loss of androgen receptor immunoexpression in affected tissues."

And 153):
"In DES-treated rats, androgen receptor (AR) immunoexpression was virtually absent from all affected tissues and the testis, whereas AR expression in controls was intense in epithelial and stromal cells. The DES-induced change in AR immunoexpression was confirmed by Western analysis for the testis."
Note: on the next page (Question) I do some calculations which show that in some cases pregnant moms were given more DES than is necessary to chemically neuter an adult human male (up to 11 times as much).

Other endocrine disrupting chemicals such as DDT also inhibits AR binding 152):
”Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist.”

If DES can inhibit androgen receptor binding or otherwise interfere with the ability of a cells androgen receptors to bind with androgen molecules, how is this different from a chemically induced equivallent of PAIS? If DES can substantially lower testosterone levels then does this not equate to the equivallent of chemically induced partial gonadal dysgenesis? Is it any wonder that the physiological effects of DES exposure are so close to those of AIS and Gonadal Dysgenesis?

It is also important to note that DES binds to and activates a cell’s estrogen receptors. In addition some people may be more resilient to the effects of estrogenic chemicals than others 175).

"A third intriguing concept from the paper by Steinmetz et al. is that there are genetic differences in susceptibility to estrogens including BPA; Fischer 344 rats are very sensitive, whereas Sprague-Dawley rats are resistant (16). The mechanism for this differential effect is unclear from the data available. The authors speculate that subpopulations of humans may likewise be more sensitive to BPA and other environmental estrogens than the population at large."

193): "The evidence is that there can be as much as a 1,000-fold, or greater, range of responses to these chemicals in different strains of mice. The regulatory default assumption of a ten-fold correction or safety factor for genetic variability is completely out of touch with the data," says Frederick vom Saal, a professor of biology at the University of Missouri-Columbia."