Circadian Stage-Dependent Effects of Epidermal Growth Factor on Deoxyribonucleic Acid Synthesis in Ten Different Organs of the Adult Male Mouse*

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Abstract
Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian stages into separate subgroups of adult male CD2F1 mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness: light, 0600–1800 h; dark, 1800–0600 h), five animals were killed at 4, 8, and 12 h after the EGF injection; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 μCi [3H]thymidine. Incorporation of [3H]thymidine into the DNA of the aorta, lung, liver, cornea, testes, kidney, parotid, thymus, spleen, and bone marrow as well as the mitotic index of the corneal epithelium was determined. The results indicate that EGF may play a role in the positive control of growth of many of these tissues, especially the aorta, lung, liver, and ornea. EGF may also play a role in inhibiting growth of the thymus, spleen, and bone marrow. Moreover, the stimulatory effect of EGF on the growth of the various tissues appears to be especially enhanced in mice injected at 1500 h and killed 4 h later at 1900 h.