Investigation of Some Amino Acid Analogues and Metabolites as Inhibitors of Wool and Hair Growth

Abstract
Sheep were given i.v. infusions of ethionine together with cycloleucine or reduced glutathione in attempts to prevent the inhibition of wool growth by ethionine. Other sheep were given cycloleucine alone to measure effects on wool growth. Compounds (22) related to cystine, methionine, ethionine, lysine, phenylalanine and tyrosine were given as i.v. infusions to sheep to investigate their potential as depilatory agents. Of these compounds, 19 were also tested in mice during their 1st cycle of hair growth. The concurrent administration of cycloleucine with ethionine prevented the weakening of wool fibers caused by ethionine, but reduced glutathione was ineffective. Cycloleucine weakened wool fibers, as judged subjectively, and caused a small reduction in fiber diameter. Selenocystine and selenomethionine caused some hair loss in mice but selenocystine was also toxic. Both seleno-amino acids were toxic for sheep; selenocystine was lethal at 0.025 mmol kg and selenomethionine at 0.09 mmol kg. Doses that permitted survival of sheep did not have depilatory effects. The presence of autophagic vacuoles in the cytoplasm of follicle bulb cells of sheep indicated that a toxic dose of selenocystine had potential depilatory activity. Other compounds investigated did not induce loss of wool or hair. Some compounds, notably 3-methylthiopropionic acid and S-(2-aminoethyl)-L-cysteine, were toxic to mice but not sheep. The methionine analogue, methoxinine (O-methyl-DL-homoserine), caused a substantial reduction in the strength of wool fibers and a prolonged alteration of the crimp pattern. Possibly cycloleucine inhibits methionine adenosyltransferase, and thereby reduces or prevents the formation of S-adenosylethionine. The failure of various compounds related to methionine and ethionine to have any depilatory activity in sheep supports the view that ethionine influences wool growth via the formation of S-adenosylethionine.