Hormone bioassays

Preliminary results of antijuvenile hormone bioassays for precocious metamorphosis in immature stages of Oncopeltus fasciatus revealed that some of the non-linear derivatives (VI) showed higher activities and lower toxicities that those exhibited by natural precocenes or 7-ethoxy-6-methoxy-2,2-dimethylchromene, one of the most active synthetic analogs known. In addition, some of these compounds were unexpectedly inactive in the sterilization bioassay with adults of the same species (8). Further investigation of antijuvenile hormone activities of selected compounds of this series in other insects is now in progress. 

Further reading Rees, L.H. and Ratter, S.J. (1978). Cyto-chemical hormone bioassays. Br, J, Hosp, Med, 19, 229... 

Structure—Activity Relationships. In spite of the considerable synthetic and bioassay effort involved in estabhshing the thyromimetic potency of thyroid-hormone analogues, more than 100 compounds have been studied (Table 2). The main stmctural requirements for thyromimetic activity can be summarized as follows (6,12—16). 

Abscisin II is a plant hormone which accelerates (in interaction with other factors) the abscission of young fruit of cotton. It can accelerate leaf senescence and abscission, inhibit flowering, and induce dormancy. It has no activity as an auxin or a gibberellin but counteracts the action of these hormones. Abscisin II was isolated from the acid fraction of an acetone extract by chromatographic procedures guided by an abscission bioassay. Its structure was determined from elemental analysis, mass spectrum, and infrared, ultraviolet, and nuclear magnetic resonance spectra. Comparisons of these with relevant spectra of isophorone and sorbic acid derivatives confirmed that abscisin II is 3-methyl-5-(1-hydroxy-4-oxo-2, 6, 6-trimethyl-2-cyclohexen-l-yl)-c s, trans-2, 4-pen-tadienoic acid. This carbon skeleton is shown to be unique among the known sesquiterpenes. 

J. Chayen, Cytochemical bioassay and its potential place in compendial definitions A method that offers sensitivity as well as specificity, in Hormone Drugs, U.S. Pharmacopeial Convention, Rockville, MD, 1982, pp. 48-58. 

The hormone itself can introduce complexity into bioassays. Many hormones must now be seen and understood not as chemical entities but as chemical pathways where hormonal activity is distributed across a number of chemical species. The more we learn about the pharmacological properties of members of a pathway, the more we are realizing that each one has a mix of common and unique properties. The practical point is that we must be careful about which hormone we choose to drive our bioassays. A hormonal chemical pathway may contain sinks as well as sources. Metabolism and uptake of a hormone can introduce significant distortions into bioassays. All of these factors leave their fingerprints on dose-response curves, and a pharmaceutical researcher developing a new bioassay has to learn to read the signs. 

So far, we have reviewed the various ways in which complex dose-response curves in intact-tissue bioassays can be the result, the pharmacological resultant, of two or more interacting activities. Now, if all that these bioassays achieved was to blur and obscure the underlying activities, they would have to give way to the newer, analytically simpler assays based on chemistry and biochemistry. However, the beauty of intact-tissue bioassays is that they are analytically tractable by using families of dose-response curves and appropriate mathematical models, the complexity of intact hormone-receptor systems can, indeed, be interpreted. Bioassay allows them to be studied as systems in ways denied to simple biochemical assays. 

The designation potential endocrine disrupter has been proposed for chemical products with an endocrine-disruption ability that is demonstrated in an in vitro assay but not confirmed in an in vivo animal model. To date, most of the available information on chemical products with endocrine disrupter activity has been generated by in vitro experiments [10]. Various existing tests and bioassays of very different types have been proposed by distinct international bodies to identify hormonal... 

Existing tests and bioassays of very distinct types have been proposed by different international bodies for the identification of hormonal mimics/antagonists, in an effort to assess the risk of exposure to... 

The development of new tests and bioassays is likely to lengthen the list of endocrine disrupters. Recent research on hormonal disruption has not only investigated estrogens and androgens as agonists and antagonists but also considered the development of the individual and the presence of compounds that interfere in other hormonal systems, such as the thyroid system. 

Many hormones lend themselves to bioassays BECAUSE... 

The quantitation of a protein that has a specific biological function, a hormone, for instance, may not give a true indication of its biological activity owing to the inactivation of some of the protein. For proteins that have definite biological functions the choice is between chemical quantitation and bioassays. For this reason the catalytic activity of an enzyme is more frequently measured than is its protein concentration. 

Possibly relevant to be added to data base in vitro bioassay general toxicity (extract) in vitro bioassay thyroid hormone disruption (extract) (incl. bioactivation) in vitro estrogenicity or androgenicity (extract) Chemicals that only are toxic in high concentration (narcotics, nanoparticles) Chemical analysis of lipophillic POPs in water... 

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