Male development just became a more complex issue, making toxic torts based on endocrine disruptors more difficult to prove

Male development just became a more complex issue, making toxic torts based on endocrine disruptors more difficult to prove

Prior posts have noted that in the arena of toxic torts causation is king.  Causation of course depends on the underlying processes.  If one cannot show a process or system is disrupted or adversely affected, then causation will not be shown.  When addressing issues related to the impacts of so-called endocrine disruptors, obviously one has to demonstrate the impacts of the disruptor in the context of human development or function.  Now, the issue vis-a-vis humans just became more complex.

It is well known that estrogen and testosterone play a role in forming the neural circuitry in developing brains, and that much of their influence occurs prior to birth.  It is also known that testosterone can be converted to estrogen in the body.  Using animal models, it has been generally assumed that a pulse of testosterone in the day or so before birth is a key event in the masculinization of the brain.  Basically, androgen receptors (which respond to "male" hormones) were "mediating" the transformation to maleness.  As such, the exposure of the mother to hormone mimics that interfere with this process has been hypothecated as leading to harm in the brain development of putative males.  Well, the picture just became more complex.

Using mice as a model, researchers found (to their surprise) that androgen receptors were nearly non-existent in the brains of newborns.  So, they looked for them earlier in the developmental process, such as when the fetal testes first started putting out testosterone; still not much.  So, they looked at mice that were genetically engineered to lack androgen receptors in their nervous system.  They had androgen receptors elsewhere in their body, so they had a masculine body, and they experienced the testosterone surge and responded to circulating testosterone.  Their brains, however, were not able to detect the presence of testosterone.  The modified mice exhibited male behavior (sexual acts, confronting other males, scent marking), but they did less of it.

The researchers thus suspect [which means of course more research] that the testosterone surge is being converted to estrogen to carryout sexual differentiation at birth.  Androgen receptors are not, thus, the master regulators of male behaviors, but instead may regulate the intensity or quantity of such behavior.  Thus, the underlying physiology of development may need to be rethought, and the hypothecated methods by which estrogen and androgen mimics interfere with development recalibrated.

The article can be found at