Inhibition of DNA synthesis in dermal tissue of Merino sheep treated with depilatory doses of mouse epidermal growth factor

ABSTRACT Two groups of three Merino wethers were infused intravenously with either 0·12 mg mouse epidermal growth factor (mEGF)/kg fleece-free body weight or 0·9% (w/v) NaCl over 24 h. Sheep treated with mEGF rejected food during treatment but feed intake was kept equal for both groups. Wool growth and plasma concentrations of mEGF were measured during the experiment. Pieces of skin taken from the wool-growing regions of the body were incubated with radioactive thymidine in order to measure its rate of incorporation into DNA. The skin was then divided at about the level of the sebaceous glands into sections that contained the upper dermis and epidermis (E sections) and those containing the generative wool-follicle bulbs (D sections). No mEGF was detected in the controls whereas mean levels of about 35 μg mEGF/l plasma were detected during the last 4 h of infusion in the protein-treated group. After infusion, wool growth was reduced by about 20% of the mean pretreatment level in the controls and no shedding of wool fibre was evident. In the mEGF-treated sheep, on the other hand, wool growth was depressed by 75–95% of the mean pretreatment level and the fleeces were almost completely cast in all three of the animals, leaving them nude on the wool-growing regions of the body. Wool growth was restored to its pretreatment level in this group about 1 month after infusion. The D sections of skin contributed 50–60% of skin wet weight in controls throughout the experiment. In the mEGF group, however, E sections increased in weight by about 25% and D sections decreased by 25%, relative to pretreatment values, during the 2 weeks after infusion. Both skin sections contributed equally to skin weight thereafter. Whereas the DNA content of E sections tended to increase after mEGF treatment there was a loss of 40%, relative to pretreatment values, in the DNA content of D sections. A significant decrease in thymidine incorporation into DNA in D sections was found, which lasted for at least 72 h after the start of infusion. Thymidine incorporation into E sections was raised during this period and again at about 10–14 days after infusion, when it was increased in both skin sections. We have concluded that the inhibition of wool growth in the mEGF-treated animals was associated with the inhibition of DNA synthesis in the dermal skin sections which contain proliferating cells of wool follicles. J. Endocr. (1984) 100, 25–31