Now that we have a toxicologist on board (DocToxyn) whose interests complement my own interests in neuroendocrinology, I think it's high time we delve into a true "hot topic," that of endocrine disruptors. I would love to set this up in a bit of a journal club format, beginning with a general review article that raises some interesting questions, but I can't find one that's freely available online, and I'm not sure if I can attach the PDF file of one without violating copyright policies on the board here. In the meantime, for those of you who have access to the the journal Toxicology, I've gotten my initial idea for a topic from this article: Fisher JS 2004 Are all EDC effects mediated via steroid hormone receptors? Toxicology, 205:33-41. EDC in the title refers to endocrine disrupting chemicals; those compounds that in some way interact with the endocrine system to alter normal functioning. (DocToxyn, feel free to add to this definition if it should be more precise). The article raises three general mechanisms through which endocrine disruptors may act: 1) interaction with a hormone receptor, either as an agonist or antagonist 2) alteration of hormone biosynthesis 3) alteration of hormone metabolism The article also points out that there is abundant evidence that endocrine disruptors are a problem for aquatic species, but far less is available to know if these disruptors are also a threat to humans. The inference is that they are indeed important for human health as well, but direct evidence is still lacking. So, I think I'll open up the topic by partially addressing the first mechanism in the above list. I haven't seen any reports indicating endocrine disruptors interact with protein hormones. I don't know if that's because this is an unlikely action, or because nobody has looked at these hormones. Rather, the focus is generally on thyroid hormones or steroid hormones (i.e., estrogens, androgens), and their receptors. Thyroid hormones receptors have a different mechanism of action than do steroid hormone receptors, particularly with regard to coactivator and corepressor interactions with the transcriptional complex located at the hormone response element. Are endocrine disruptors, in the context of hormone interactions, thought to interact primarily with the with receptor to induce a conformational change similar to that of an agonist or antagonist, or are there disruptors that act directly upon cofactor/transcriptional regulators binding to the hormone response element? I haven't come across anything that indicates anyone has looked beyond actions of disruptors as receptor ligands. Perhaps DocToxyn has seen or heard something that isn't published but known among toxicologists about this. Has anyone even looked at interactions beyond that of a ligand-receptor interaction? I ask, because it's possible someone has looked and found they don't act at that level, so never published it. Or, it's possible nobody has gotten around to looking yet, considering this is a field still in its infancy. PLease, let's try to keep this thread on-topic. However, by that, I mean general questions necessary to understand the topic are fair game. For example, if a more basic endocrinology tutorial is needed to understand the topic, or if you need further definitions of terminology used, ask away! And, please, feel free to bring in your own interests and expertise to this discussion. That's the whole point! This is a topic that is very interdisciplinary, so we can easily discuss any facet of this, including: endocrinology, toxicology, developmental biology, molecular biology, cancer biology, etc. Bonus points to those who take time to delve into the literature and use peer-reviewed sources as references.