Physiology 5th Ed.

REGULATION OF HORMONE RECEPTORS

The previous section describes the mechanisms that regulate circulating levels of hormones, usually by negative feedback. Although circulating hormone levels are important, they are not the only determinant of the response of a target tissue. To respond, a target tissue must possess specific receptors that recognize the hormone. Those receptors are coupled to cellular mechanisms that produce the physiologic response. (The coupling mechanisms are discussed in the section on mechanisms of hormone action.)

The responsiveness of a target tissue to a hormone is expressed in the dose-response relationship in which the magnitude of response is correlated with hormone concentration. As the hormone concentration increases, the response usually increases and then levels off. Sensitivity is defined as the hormone concentration that produces 50% of the maximal response. If more hormone is required to produce 50% of the maximal response, then there has been a decrease in sensitivity of the target tissue. If less hormone is required, there has been an increase in sensitivity of the target tissue.

The responsiveness or sensitivity of a target tissue can be changed in one of two ways: by changing the number of receptors or by changing the affinity of the receptors for the hormone. The greater the number of receptors for a hormone, the greater the maximal response. The higher the affinity of the receptor for the hormone, the greater the likelihood of a response.

A change in the number or affinity of receptors is called down-regulation or up-regulation. Down-regulation means that the number of receptors or the affinity of the receptors for the hormone has decreased.Up-regulation means that the number or the affinity of the receptors has increased. Hormones may down-regulate or up-regulate their own receptors in target tissues and even may regulate receptors for other hormones.

Down-Regulation

Down-regulation is a mechanism in which a hormone decreases the number or affinity of its receptors in a target tissue. Down-regulation may occur by decreasing the synthesis of new receptors, by increasing the degradation of existing receptors, or by inactivating receptors. The purpose of down-regulation is to reduce the sensitivity of the target tissue when hormone levels are high for an extended period of time. As down-regulation occurs, the response to hormone declines, although hormone levels remain high. An example of down-regulation is the effect of progesterone on its own receptor in the uterus (seeChapter 10).

Down-regulation can also refer to a hormone’s effect on receptors for other related hormones. This type of down-regulation also is illustrated by progesterone. In the uterus, progesterone down-regulates its own receptor and down-regulates the receptors for estrogen. A second example of this type of down-regulation is seen in the thyroid system: Triiodothyronine, or T3, decreases the sensitivity of thyrotropin-releasing hormone (TRH) receptors in the anterior pituitary. The overall effect is that chronically high levels of T3 reduce the overall responsiveness of the hypothalamic-pituitary-thyroid axis.

Up-Regulation

Up-regulation of receptors is a mechanism in which a hormone increases the number or affinity of its receptors. Up-regulation may occur by increasing synthesis of new receptors, decreasing degradation of existing receptors, or activating receptors. For example, prolactin increases the number of its receptors in the breast, growth hormone increases the number of its receptors in skeletal muscle and liver, andestrogen increases the number of its receptors in the uterus.

A hormone also can up-regulate the receptors for other hormones. For example, estrogen not only up-regulates its own receptor in the uterus, but it also up-regulates the receptors for LH in the ovaries.