Human Biochemistry Volume 2 - Murray R. 1993

Biochemistry of Intracellular and Intercellular Communications
Action of Hormones
Mechanism of Action of Group II Hormones (Peptide Hormones) - Hormones with an Unknown Intracellular Mediator

For many important Hormones, the intracellular messenger has not yet been identified. Interestingly, these hormones fall into two distinct groups. One comprises Insulin, Insulin-like Growth Factors (IGF-1 and IGF-2), and several other growth factors, all of which apparently share a common ancestral precursor. The other major group consists of Proteins genetically belonging to the Growth Hormone family (growth hormone, prolactin, chorionic somatomammotropin), which are clearly related to one another (see Chapter 45). These groups overlap to some extent, as IGF-1 apparently mediates many of the effects of growth hormone. Oxytocin belongs to neither the first nor the second group.

A tremendous amount of effort has been devoted to identifying the intracellular messenger of insulin. A wide range of compounds has been proposed as candidates for this role: cAMP, cGMP, H₂O, Ca²⁺, and insulin itself. There have been repeated reports of the isolation from tissue extracts of various "mediators"—protein or phospholipid derivatives—yet to date, none of these has been fully isolated and characterized. It was recently discovered that the Insulin Receptor possesses intrinsic Tyrosine kinase activity, which sparked interest in searching for a phosphorylation cascade that could explain The Mechanism of insulin action. This observation is by no means isolated, since epidermal growth factor also exhibits tyrosine kinase activity, thereby stimulating further research into the insulin receptor. It is worth noting that platelet-derived growth factor is also a tyrosine kinase, bearing a striking resemblance to the specific oncogene products v-sis and c-sis (of viral and cellular origin, respectively). When target Cells (such as fibroblasts, glial cells, or smooth Muscle cells) are exposed to this growth factor, they synthesize the products of several genes involved in subsequent Cell Replication.

In all likelihood, the action of this large group of hormones relies on entirely different mechanisms of Intracellular Signaling, but traditional messengers are definitely not involved.

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