5 cell signaling and the hormonal responses to exercise. Neuroendocrine system: endocrine system releases hormones into blood to circulate to tissues, nervous system uses neurotransmitters to relay messages from one nerve to another. Endocrine glands: release hormones directly into the blood. Effect of a hormone on tissues is determined by the plasma concentration and number of active receptors. Plasma concentration is determined by the following : rate of secretion of hormone from endocrine gland, magnitude of input, stimulatory versus inhibitory input, rate of metabolism (clearance) to excretion of hormone. Hormones only affect tissues that contain specific hormone receptors. Magnitude of effect is dependent on : concentration of the hormone, number of receptors on the cell, affinity of the receptor for the hormone. Downregulation : decrease in receptor number or affinity in response to high concentration of hormones. Upregulation : increase in receptor number or affinity in response to low concentration of hormones.