To maintain homeostasis, the secretion of hormones must be turned on and off as needed. Adjustments in secretory rates may be accomplished by neural mechanisms or by feedback mechanisms. Neural mechanisms are illustrated by the secretion of catecholamines, where preganglionic sympathetic nerves synapse on the adrenal medulla and, when stimulated, cause secretion of catecholamines into the circulation. Feedback mechanisms are more common than neural mechanisms. The term “feedback” means that some element of the physiologic response to a hormone “feeds back,” either directly or indirectly, on the endocrine gland that secreted the hormone, changing its secretion rate. Feedback can be negative or positive. Negative feedback is the most important and common mechanism for regulating hormone secretion; positive feedback is rare.
The principles of negative feedback underlie the homeostatic regulation of virtually all organ systems. For example, in Chapter 4, negative feedback is discussed in the regulation of arterial blood pressure in which small changes in blood pressure turn on, or activate, mechanisms that will restore blood pressure back to normal. A decrease in arterial blood pressure is detected by baroreceptors, which activate coordinated mechanisms that increase blood pressure. As blood pressure returns to normal, a disturbance is no longer sensed by the baroreceptors and those mechanisms previously activated will be turned off. The more sensitive the feedback mechanism, the smaller the “excursions” of blood pressure above or below normal.
In endocrine systems, negative feedback means that some feature of hormone action, directly or indirectly, inhibits further secretion of the hormone. Negative feedback loops are illustrated in Figure 9-3. For illustrative purposes, the hypothalamus is shown in relation to the anterior pituitary, which is shown in relation to a peripheral endocrine gland. In the figure, the hypothalamus secretes a releasing hormone, which stimulates secretion of an anterior pituitary hormone. The anterior pituitary hormone then acts on a peripheral endocrine gland (e.g., the testis) to cause secretion of the hormone (e.g., testosterone), which acts on target tissues (e.g., skeletal muscle) to produce physiologic actions. The hormones “feed back” on the anterior pituitary and the hypothalamus to inhibit their hormonal secretions. Long-loop feedback means that the hormone feeds back all the way to the hypothalamic-pituitary axis. Short-loop feedback means that the anterior pituitary hormone feeds back on the hypothalamus to inhibit secretion of hypothalamic-releasing hormone. Not shown in the figure is a third possibility called ultrashort-loop feedback, in which the hypothalamic hormone inhibits its own secretion (e.g., growth hormone–releasing hormone [GHRH] inhibits GHRH secretion).
Figure 9–3 Negative and positive feedback mechanisms. The hypothalamic-pituitary axis is used as an example in this illustration. Solid lines and plus (+) signs indicate stimulation; dashed lines and minus (−) signs indicate inhibition.
The net result of any version of negative feedback is that when hormone levels are judged (by their physiologic actions) to be adequate or high, further secretion of the hormone is inhibited. When hormone levels are judged to be inadequate or low, secretion of the hormone is stimulated.
There are other examples of negative feedback that do not utilize the hypothalamic-pituitary axis. For example, insulin regulates blood glucose concentration. In turn, insulin secretion is turned on or off by changes in the blood glucose concentration. Thus, when blood glucose concentration is high, insulin secretion from the pancreas is turned on; insulin then acts on its target tissues (liver, muscle, and adipose) to decrease the blood glucose concentration back toward normal. When the glucose concentration is sensed as being low enough, insulin is no longer needed and its secretion is turned off.
Positive feedback is uncommon. With positive feedback, some feature of hormone action causes more secretion of the hormone (see Fig. 9-3). When compared with negative feedback, which is self-limiting, positive feedback is self-augmenting. Although rare in biologic systems, when positive feedback does occur, it leads to an explosive event.
A nonhormonal example of positive feedback is the opening of nerve sodium (Na+) channels during the upstroke of the action potential. Depolarization opens voltage-sensitive Na+ channels and causes Na+entry into the cell, which leads to more depolarization and more Na+ entry. This self-reinforcing process produces the rapid, explosive upstroke.
In hormonal systems, the primary example of positive feedback is the effect of estrogen on the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary at the midpoint of the menstrual cycle. During the follicular phase of the menstrual cycle, the ovaries secrete estrogen, which acts on the anterior pituitary to produce a rapid burst of FSH and LH secretion. FSH and LH have two effects on the ovaries: ovulation and stimulation of estrogen secretion. Thus, estrogen secreted from the ovaries acts on the anterior pituitary to cause secretion of FSH and LH, and these anterior pituitary hormones cause more estrogen secretion. In this example, the explosive event is the burst of FSH and LH that precedes ovulation.
A second example of hormonal positive feedback is oxytocin. Dilation of the cervix causes the posterior pituitary to secrete oxytocin. In turn, oxytocin stimulates uterine contraction, which causes further dilation of the cervix. In this example, the explosive event is parturition, the delivery of the fetus.