METABOLIC FEEDBACK IN MAMMALIAN ENDOCRINE SYSTEMS

Information processing through feedback loops is an integral part of most endocrine systems, and ranges from simple negative loops to complex combinations of negative and positive loops. Moreover, feedback may occur at local (paracrine) or long-distance sites, and with multiple time-domains. Traditionally, feedback is visualized as one hormone stimulating release of a second hormone, which then circulates in the blood to carry out various biological activities, one of which is to inhibit further secretion of the first hormone. This represents a fail-safe mechanism to protect the organism against the potentially damaging effects of uncontrolled secretion of many of the common hormones, some of which are highly catabolic or anabolic. However, it is becoming increasingly apparent that the products of catabolism and anabolism may themselves participate in the feedback process in either a feed-forward or feedback manner. For example, free fatty acids are liberated by the action of growth hormone, and in turn are potent inhibitors of growth hormone secretion (feedback). On the other hand, stress activates adrenal cortical and medullary secretion, which also promotes lipolysis, but in this case the liberated free fatty acids may actually stimulate the system further (feed-forward). Similarly, glucose has been shown to directly inhibit the activity of several different endocrine pathways, and must now be considered an integral part of the overall regulatory mechanism involved in fine-tuning secretion and possibly production of hormones. By constructing models of feedback of increasing complexity, it is possible to make predictions about previously unrecognized relationships between hormones and products of metabolism.