[Heterogeneity of protein hormones in radioimmunoassay]

Radioimmunoassay measures antigenic determinants of hormonal molecules in the plasma and tissues. These estimations carried out after fractionation in biological fluids, have revealed several immunological forms of the same hormone. These immunoreactive forms may be added to already well known elements of hormonal heterogeneity: formation of aggregate, polymerisation, links to transport proteins, microheterogeneity by silent mutation. The main problem is in the relationship of the various immunoreactive forms to the same hormonal sequence. The similar immunoreactive forms of high molecular weight (big hormone) usually have low biological activity and suggest the presence of prohormone; the suggestion of prohormonal nature depends on the chronology of the incorporation of labelled leucine and enzymatic transformation of prohormone with low biological into active hormone. The forms with high molecular weight and similar immunological activity may be of another nature. Thus, it has been shown that the biosynthetic nature of a compound such as big big insulin in the rat is doubtful owing to the absence of specific incorporation of labelled leucine into the immunoprecipitate of this fraction. The significance of low molecular weight forms is still little known. There may be breakdown products, biologically active products or biosynthetic products. An example of these forms is supplied by the existence of an alpha sub-unit of gonadotrophin present in the plasma of menopausal women. The interest of analytical methods by radio-receptor, stimulation of cyclase activity in the identification of biological activity of immunoreactive forms, is discussed in relation to immunological forms of enteroglucagon. An unusual aspect of the evolutive and adaptative character of hormonal heterogeneity is given by the gastro-intestinal hormones: secretin, vasoactive intestinal polypeptide and enteroglucagon, have similar structure and mode of action; however, the existence of a specific receptor is a sign of their functional differentiation at molecular level.