K

For some endocrine systems, the concentration of the plasma transport protein can be subject to physiological regulation, i.e., the concentration of PTP can be either increased or decreased. Thus, changes in the amount of PTP can, in principle, alter the amount of "free" H, as described by the relationships of Eq. (6).

The current view is that it is the "free" form of steroid hormones and not the conjugate of the hormone with its PTP that enters target cells to begin the sequence of steps that results in the generation of a biological response. Entry of steroid hormones through the target cell membrane may occur by a process of free diffusion, but the exact mechanism is still not known.

B. Receptor-Mediated Transmembrane Signaling

This section of Chapter 1 presents current understanding of the several pathways of signal transduction involving membrane-based receptors. These include receptors that couple to (a) adenylate cyclase, (b) gua-nylate cyclase, (c) the phosphoinositide pathway, (d) the utilization of intracellular Ca2+ as a second messenger, and (e) ion channels. These topics will be presented sequentially. Table 1-6 tabulates the hormones that activate the various specific signal transduction pathways. A given hormone-receptor system may utilize more than one signaling pathway.

1. G-Proteins

A key participant in all of these signal transduction pathways is a family of G proteins. When the membrane receptor becomes occupied, the resulting confor-

1. General Considerations of Hormones

TABLE 1-8 Pharmacological Agents That Interact with G Proteins

Agent Consequence of action

Cholera toxin Increased production of cAMP by adenylate cyclase Pertussis toxiifilockage of action of hormone working through Gj

NaF Inactivation of both Gs and Gj mational change results in the receptor coming into contact with a G protein; an example is presented in Figures 1-34 and 1-36. The G proteins consist of an oligomer with three subunits, designated a, fi, and y, with a total molecular weight of approximately 80,00095,000 (a « 45,000, j8 « 35,000, y « 5000). Functionally the G proteins are the true signal transducers since they respond to the occupancy of the receptor and modulate the activity of the catalytic subunit of the membrane-bound adenylate cyclase (AC) enzyme. There are two functions of the a-subunit: G„s, which activates the AC, and Gai/ which inhibits the activity of AC. Both G„s and G„, are activated by guanosine triphosphate (GTP) and both also function as a GTPase. The GTPase activity endows the G proteins with a turn-off mechanism. The functions of the /3- and y-

Hormone Receptor

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