The Interaction between Hormone and Receptor

The binding of a hormone to a receptor can in most cases be described by the simple reaction scheme  

The switch for the activation of an intracellular signaling pathway is in most cases an increase in the concentration of the freely circulating hormone. This leads to an increase in the concentration of the hormone-receptor complex, which results in an increased activation of subsequent reactions in the cell. The concentration of the circulating hormone is thus the main regulatory parameter in cellular conummication. The relation between hormone concentration, binding of the hormone to the receptor, and subsequent reaction in the cell is illustrated in fig. 3.7 for the case of adrenaline and the P-adrenergic receptor. 

An increase in the hormone concentration is the main regulating element when a rapid activation of a signaling pathway is required. Hormones can be stored in the 

---

For these equations to be valid, a number of conditions must be met, as outlined by Kahn (1975). Actually, the interaction between hormone and receptor is usually much more complex than can be explained by this simple bimolecular equation. However, this simple bimolecular relationship seems to exist with regard to the receptors for growth hormone (Lesniak et al., 1974), prolactin (Shiu and Friesen, 1974), LH-hCG (Rao and Saxena, 1973), calcitonin (Marx et al., 1974), and the jS-adre-nergic receptor in some tissues (Brown et al., 1976b Aurbach et al., 1974). 

The locus of the encounter between hormone and receptor may be extracellular, cytosolic, or nuclear, depending on the hormone type. The intracellular consequences of hormone-receptor interaction are of at least six general types (1) a change in membrane potential results from the opening or closing of a hormone-gated... 

Glucagon storage granules become unstable at high dilutions in the circulation, and the circulating hormone must exist mostly as monomers with little defined secondary structure. Receptor binding studies indicate hydro-phobic interactions between hormones and receptor. Work by Rodbell et al (1971) and Epand and Jones (1977) has shown that almost the entire molecule is required for full biological potency, since NH2-terminal or COOH-terminal modifications lead to decreased receptor potency, as does modi-... 

The Interaction Between Glucagon and its Binding Site - The interaction between a hormone and its receptor must ultimately be described in terms of specific intermolecular forces between the two structures. This ideal has not been achieved in the case of polypeptide hormones for many reasons, not the least of which is the complexity of peptide hormone molecules. Fortunately, several fragments of glucagon have recently become available, and these have provided important clues regarding intermolecular forces. 

Other loci where their interaction with specific receptors (located in target cells) triggers off many biochemical reactions quantitative modification of physiological activity, tissue growth or qualitative alteration of cellular structure and/or function. In that sense, the distinction between hormones and other chemical mediators of cell interaction, such as neural transmitters or embryonic-inducing factors, becomes fuzzy . It rests mainly on the concept of transport. 

The term endocrine disrupter (ED) has tended to be used for those chemicals which act specifically at the level of the hormone receptor present in the target cells of various organs. Such chemicals may either mimic the action of the natural hormone (agonistic activity) or are sufficiently similar in molecular shape to the naturally produced hormone to interfere with the interaction between the hormone and receptor, thus blocking or impeding the activation of the receptor (antagonsitic activity). Such effects may occur at very low concentrations (as with the endogenous hormone), compared with the concentrations normally required to elicit the more traditional toxic effects attributed to chemicals. Recently,... 

The complex between GH and GHR contains one molecule of the hormone and two molecules of the receptor, even though the hormone does not have a pseudosymmetric structure with two similar binding sites. Instead, there are two completely different binding sites on the hormone, each of which binds to similar sites on the receptor molecules. These interactions are so far unique. 

Russell J et al Interaction between calcium and 1,25-dihydroxy-vitamin D3 in the regulation of preproparathyroid hormone and vitamin D receptor mRNA in avian parathyroids. Endocrinology 1993 132 2639. 

Dimerization is a process necessary for the receptor to carry out its interaction with DNA and to initiate the response to the hormone. Dimerization occurs when the receptor monomer has freed itself of hsp90 and the other accompanying proteins forming the structure of the native receptor. Moreover, binding to the hormone provides the receptor with the necessary three-dimensional structure to produce the interaction between the two receptor monomers (Kuiper et al. 1996 O Malley 1990). 

Weigent, D.A. and Blalock, J.E., Interactions between the neuroendocrine and immune system common hormones and receptors, Immunol. Rev., 100, 79, 1987. 

---