Growth hormone paradigm

Fig. 1. Grouping of hematopoietic cytokine receptors by shared receptor usage. The majority of the hematopoietic cytokine receptors incorporate one of three shared signaling receptors, either the common beta (/ c) chain, the common gamma (7,-) chain or gplSO. The crystal structure of the growth hormone (red) complex (inset) was the first structure of a four helix bundle cytokine in complex with its receptor (green) (de Vos et al, 1992) and established the paradigm of cytokine/receptor complex formation. (See Color Insert.)...

The growth hormone structure established the architecture of the site I and II interactions in a homodimeric receptor complex. The viral and human IL-6 complexes with gplSO extend this paradigm to heterodimeric complexes but also elaborate the modular epitope concept by adding the site III. It is clear from the gplSO complexes that in the case of the HHV-8 IL-6, a site II is used for the gplSO GHR contact. In the human structure, a site I is used for the a. receptor and a site II is used for the gplSO GHR interaction. Similar to GH, in the human IL-6 structure, precomplexation... 

In the 1980s numerous impediments were overcome to provide controlled-release peptide dosage forms, which has changed the paradigm of drug delivery for many of these important drugs, i.e., particularly leuprolide for treatment of prostate cancer. Over the last 10 years, numerous impediments to controlled-release of proteins have been similarly identified, and several solutions demonstrated, as evidenced by the marketed Nutropin Depot formulation for growth hormone, and some of the examples described... 

Hormones provide a form of communication between different cells and from one organ to another. The dramatic effects of hormones on physiological functions such as growth and metabolism have promoted studies to elucidate their sources of production, sites of action, and how they are controlled. Becanse hormones exert their effects by binding to specihc receptors, studies defining their mechanisms of action have also provided important paradigms for how receptors activate intracellular signaling cascades that lead to altered cellular responses. 

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