Syndromes of androgen resistance.

Androgen resistance can be divided into two broad categories: deficiency in 5 alpha-reductase and defects in the androgen receptor. Studies of these two disorders have provided insight into both the normal pathway of androgen action and into the pathogenesis of abnormal sexual development. 5 alpha-Reductase deficiency is a rare autosomal recessive disorder involving the 5 alpha-reductase 2 enzyme; affected males exhibit a defect in virilization most evident as impairment of the virilization of the external genitalia and urogenital sinus. Disorders of the androgen receptor in genetic males cause a spectrum of developmental abnormalities that vary from phenotypic females to men with mild defects in virilization. On functional grounds we have divided these defects into absence of receptor function, qualitatively abnormal receptors, quantitative defects in receptor amount, and apparently normal receptor. Cloning of the cDNA for the receptor and application of the polymerase chain reaction techniques for sequencing of mutants made it possible to analyze these defects at the molecular level. It is now apparent that the functional categorization underestimated the complexity of the mutations. Indeed, major gene deletions and/or rearrangements, single amino acid substitutions, and premature termination codons all can cause variably severe functional abnormalities.     

Pharmacology of anthelmintic resistance.

Anthelmintic resistance has grown from a curiosity to an important economic problem in several animal industries and is now set to threaten the control of human parasites. The pharmacology of anthelmintics and anthelmintic resistance has been studied most extensively in the nematode parasites of sheep. Here, Nick Sangster and Jenny Gill discuss this veterinary experience, summarizing the progress made in understanding anthelmintic resistance and highlighting the tools available for research.     

Genetics of resistance to tetraethyllead.

A Drosophila melanogaster population was exposed for 25 generations to 60 micrograms tetraethyllead per gram of medium. Selection over this period resulted in an increase in fecundity, hatchability and larva-to-adult viability. Chromosome assay showed that response in these traits was generally under additive genetic control in conformity with existing results in the literature on the genetics of resistance to acute environmental stress in D. melanogaster.