Methoprene

Hartwick College Research

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Many scientists working on the deformed frog problem believe that the cause is a chemical one. One of the most likely chemical candidates for causing such deformities is methoprene, a synthetic insect growth hormone (IGH) that is sprayed in problem areas in order to control pests such as mosquitos and fleas. But how could methoprene cause frogs to sprout extra legs???  

In the tadpole, vitamin A (a retinoid) is transformed into all-trans retinoic acid and 9-cis retinoic acid. Once inside the cell, all-trans RA binds to a specific receptor called RAR and 9-cis RA binds to another receptor called RXR. The bound RAR and RXR then join together to form a "heterodimer" complex that can bind to DNA and turn genes on or off. Methoprene mimics IGH and can bind to RXR as if it were a retinoid. The hypothesis is that this can substitute for the 9-cis RA and form a heterodimer with RAR. Furthermore, it is hypothesized that this can affect where, or the way that the complex attaches to the DNA. So this can cause amphibians to grow extra limbs...how? Some developmental biologists have come up with a limb development model called the "The Morphogen Gradient Model". This model states that a morphogen gradient is present across the entire limb bud as it develops. The concentration of the morphogen at any given point in that limb bud determines the developmental fate of the cells. The area with the highest concentration is in the posterior of the limb bud and is called the Zone of Polarizing Activity (ZPA).  

     The ZPA secretes a morphogen that diffuses from its source to form a concentration gradient from the posterior      end to the anterior end of the limb bud. Those cells nearest the ZPA would be exposed to the highest amount of      this compound, whereas those farthest from the ZPA would be exposed to a relatively low concentration. (Gilbert      1994)  

It appears that the gene that is doing the work in the ZPA is one called sonic hedgehog or shh. Shh "tells" surrounding cells if they are supposed to be anterior or posterior cells. Here's what makes the methoprene hypothesis work: It turns out that retinoic acid can turn on sonic hedgehog! So, if methoprene, which acts like RA, is present in high enough concentrations in the limb bud, it could induce shh to turn on in the wrong place. This would cause the cells to "think" that they were supposed to be something else, leading to deformities!  

It is very important that this hypothesis be immediately researched. The good news of the situation is that the methoprene/RA mimic scenario seems unlikely. This is very good news because the alternative has horrendous implications for all organisms that share the environment with frogs, including people. The bad news is that the simple possibility that this could be correct is so terrible that we just cannot afford to ignore it completely. If methoprene or an RA mimic is causing causing these problems, then the deformed amphibians are telling us something of extreme importance, and we need to do something to counteract the situation.

http://www.hartwick.edu/biology/def_frogs/meth/meth.html

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