Adenyl cyclase hormone receptor model

In addition to the importance of this work in endocrinology, the study of hormone-sensitive adenyl cyclase systems offers certain advantages as a model for all types of receptors, viz, hormone receptors other than adenyl cyclase, drug receptors, and neurotransmitter receptors. 

The mobile receptor model was proposed by Cuatrecasas and by De Haen in an attempt to explain why so many different drugs, hormones, and neurotransmitters can activate adenylate cyclase. According to classical concepts, a recognition site is permanently associated with an effector site, and will regulate its operation on a one-to-one or some other stoichiometric basis. The recognition site is, of course, specific. 

Hormones may act on different types of receptors in the cell The effects of the hormones would result from the binding of the hormone to one or to several types of receptors. The two identified receptors of adrenaline (a, fi) provide good examples of such a model (see Sect B, Chap. S.2). Another hypothesis, plausible for polypeptide hormones, would be that the different parts of the hormone could mteract at one site with corresponding receptors. This implies that the hormone is a complex molecule carrying several messages. Such a model has been put forward to explain the concomitant activation of amino add and glucose transport systems, and inhibition of adenyl cyclase by insulin in the plasma membrane of the fat celL For most hormones, it is not known which model may apply. However, recent data show that the effects of several hormones may be explained by the activation of... 

Lefkowitz, R. J., Roth, J., and Pastan, I., 1971, ACTH-receptor interaction in the adrenal A model for the initial step in the action of hormones that stimulate adenyl cyclase, Ann. N. Y. Acad. Sci. 185 195. 

The general relationship between the membrane-boimd hormone receptor and intracellular events produced by hormone binding to this receptor is depicted in Fig. 1. This model was suggested by Robison et al. (1967) and is composed of two subunits. The subunit in contact with the external enviroment is the hormone receptor and is the regulatory portion of the complex. Located in the inner portion of the plasma membrane and in contact with the intracellular environment is the effector or catalytic component which, in most cases, is adenylate cyclase. There is a third portion of the model which recent studies have elucidated and which is discussed in section B (p. 564). 

Figure 2. General model of activation of adenylate cyclase by hormones. The hormone receptor (R) is located in the outer portion of the phospholipid bilayer while the adenylate cyclase is in the inner part of the bilayer. Ac (i) represents inactive adenylate cyclase Ac(a) represents hormone-activated adenylate cyclase H represents the hormone.

Bimbaumer, L., 1973, Hormone-sensitive adenylate cyclase, useful models for studying hormone receptor functions in cell free systems, Biochim. Biophys. Acta 300 129. 

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