Nearby construction influences the physiology of research animals: beyond stress hormones.

A dirty little secret in science is that there are many factors beyond the control of researchers that may compromise the results of even carefully controlled experiments. Although the methods sections of scientific papers tend to overlook the fact, researchers are not in complete control of the environment of research animals. Everything from nearby construction (1, 2) to shipping during particular developmental stages has been shown to influence (3) is suspected of influencing (4, 5) a wide variety of dependent variables. In as systematic an experiment as is possible considering the vagaries of building construction or renovation, in this issue of Endocrinology, Raff et al. (6) have again raised the important issue and documented the physiological effects of one serious impediment to animal research, environmental factors that the researcher cannot control. Here the investigators provide positive evidence that nearby construction can be devastating to experiments. During a 3-month construction project near their animal facility, the plasma levels of ACTH, corticosterone, and aldosterone in their rats each doubled or tripled contrasted with the period before or after the construction. In contrast to a previous report of the effects of construction (1), no effect was seen on body weight during construction. Similarly, no effect was seen on plasma renin, CRH mRNA in the hypothalamus, POMC mRNA in the anterior pituitary, or on a variety of genes in the pituitary and adrenal gland. Nevertheless the effects on plasma levels of ACTH, corticosterone, and aldosterone were quite dramatic. The paper by Raff et al. (6) should serve as another wake-up call to researchers, administrators, and planners that the effects of nearby construction can be devastating to experimental results. During nearby construction, the researcher or others in the animal room may not hear noise or feel vibrations, or a construction worker or planner may believe that the work will have no influence on the experiments. Unfortunately, this does not mean that the animals are not influenced physiologically. Often these stressors are ignored by researchers who do not work on stress. It could be argued that only those individuals who study stress should be concerned about the effects of stressors associated with construction, and those who do not study stress need not be concerned. However, it can also be argued that it is unwise to draw the conclusion from studies like that of Raff et al. (6) that construction affects only stress systems. The increase in levels of ACTH, corticosterone, and aldosterone reported by Raff et al. (6) undoubtedly have secondary effects on other systems influenced by these hormones. As one example, corticosterone influences neurogenesis within the hippocampus (7). Consequently, it is likely that the results of experiments on hippocampal-associated memory would also be influenced by the construction stress. Similarly, because prenatal stressors can alter the levels of plasma testosterone in fetal rats (8), and consequently the sexual differentiation of the brain (9) and behavior (10), researchers working on sexual differentiation of the brain or behavior or on any physiological or behavioral endpoint that is sexually differentiated should be concerned about prenatal stress associated with nearby construction. There are sometimes stressors that researchers not only cannot control, but that they may not even know about. A few years ago, my research group was in the middle of a quite large, parametric experiment to determine the ideal paradigms and doses of ovarian hormones for inducing