The Hypothalamic-Pituitary-Target Gland Axis

In the hypothalamic-pituitary-target gland axis, a second negative feedback loop is superimposed on the first negative feedback loop. In this second loop, the target gland hormone binds to nerve cells in the hypothalamus, thereby inhibiting the secretion of specific hypothalamic-releasing hormones (neurohormones) that stimulate the secretion of pituitary hormones (an important element in the first negative feedback loop). The hypothalamic neurohormones are released within a set of veins that connects the hypothalamus to the pituitary gland (the hypophyseal-portal circulation), and therefore the neurohormones reach the pituitary gland in high concentrations. Target gland hormones effect the secretion of hypothalamic hormones in the same way that they effect the secretion of pituitary hormones, thereby reinforcing their effect on the production of the pituitary hormone.

The importance of the second negative feedback loop lies in the fact that the nerve cells of the hypothalamus receive impulses from other regions of the brain, including the cerebral cortex (the centre for higher mental functions, movement, perceptions, emotion, etc.), thus permitting the endocrine system to respond to physical and emotional stresses. This response mechanism involves the interruption of the primary feedback loop to allow the serum concentrations of hormones to be increased or decreased in response to environmental stresses that activate the nervous system. The end result of the two negative feedback loops is that, under ordinary circumstances, hormone production by target glands and the serum concentrations of target gland hormone are maintained within very narrow limits but that, under extraordinary circumstances, this tight control can be overridden by stimuli originating outside of the endocrine system.