Endocrine considerations in toxicologic pathology.

Abstract

Detection of xenobiotic-induced toxicity on the endocrine system is a very difficult task because of the close relationship that the endocrine system has with the neural and immune systems. This is further complicated when one is asked to extrapolate from lab animals to man. Knowledge across species of hormonal action, solubility, transportation, plasma half life, receptor location, type of mediator, rhythmicity and pattern of secretion, is essential. One hormone can exert various effects in different tissues, or one function can be regulated by several hormones or even many functions of one endocrine target tissue can be regulated by several hormones acting in concert. The endocrine toxic response is determined by the state of differentiation of the target site. Feedback mechanisms both positive and negative, should also be taken into consideration initially. Because the effects of hormones have wide-ranged ramifications, the toxic responses likewise encompass broad areas such as the regulation of energy availability, maintenance of the internal environmental, development, growth and reproduction. The initial step involves the ascertaining of interference with the general trophic and target gland function and the characterization of the primary toxic effect. Equally important is to calculate the dose which elicited this primary effect, taking into consideration the area under the curve of the target endocrine site. Adapting this step-by-step approach, the causality between a specific toxic dose and a specific toxic effect can be readily and reliably established across all lab animal species and man.