The Effects of Intradermal Injections of Spermidine on the Growth Rate of Fibers and Mitosis of Wool Follicles in Merino Lambs

The study involved generating a transgenic mouse line overexpressing the SSAT gene under a mouse metallothionein I promoter, leading to significant changes in tissue polyamine pools and delayed permanent hair loss compared to previous models. The liver was notably affected, with altered polyamine levels. Despite high SSAT mRNA levels, enzyme activity was only moderately increased unless induced by ZnSO4 or the polyamine analogue DENSPM, which caused a dramatic increase in enzyme activity and depletion of liver polyamines, resulting in high mortality and liver damage. The findings suggested that SSAT overexpression made the mice highly sensitive to polyamine analogues, indicating a post-transcriptional regulation mechanism.

In this study, researchers created a transgenic mouse line that overexpressed spermidine/spermine N^1-acetyltransferase, leading to significant alterations in tissue polyamine pools. These changes included the presence of N^1-acetylspermidine, an unusual accumulation of putrescine, and reduced levels of spermidine and spermine. The most notable phenotypic effect was permanent hair loss in mice aged 3 to 4 weeks, associated with the formation of follicular cysts in the dermis, likely due to putrescine's interference with hair follicle cell differentiation and proliferation. Additionally, female mice were infertile, linked to ovarian hypofunction and underdeveloped uteri. This research highlighted the potential of using spermidine/spermine N^1-acetyltransferase overexpression to manipulate polyamine levels in transgenic animals for studying developmental and cancer-related outcomes.

The study investigated the role of polyamines in hair follicle function and fiber composition in sheep. It found that inhibiting ornithine decarboxylase with alpha difluoromethylornithine altered fiber characteristics but did not inhibit wool follicle growth in culture. Conversely, inhibiting S-adenosylmethionine decarboxylase with methylglyoxal (bis)guanylhydrazone completely inhibited fiber growth, which could be reversed by adding spermidine, but not spermine. The study concluded that polyamines, particularly spermidine, were crucial for hair growth, as evidenced by the ability of spermidine to partially counteract growth depression in methionine-deficient conditions.