Involvement of developing sympathetic nervous system in thyroxine-mediated submandibular gland nerve growth factor and epidermal growth factor responses.

Thyroxine (T4) administration in mice during the 2nd wk of postnatal life elicits a precocious increase in submandibular gland-nerve growth factor (SMG-NGF) and epidermal growth factor (SMG-EGF) levels, but the mechanism(s) of T4 action has not been studied. The present report examines the role of the developing sympathetic nervous system (SNS) in the SMG-NGF and EGF responses to T4. For this purpose newborn mice were injected with T4 and/or 6-hydroxydopamine, a toxic congener of norephinephrine which causes selective destruction of sympathetic nerve terminals. The effectiveness of chemical sympathectomy was assessed by SMG-norepinephrine measurements using a sensitive radioenzymatic assay. The glandular norepinephrine contents were greatly reduced indicating that the dose and duration of 6-OHDA treatment were sufficient to cause a total sympathectomy in SMG tissue. In addition, the 6-OHDA treatment greatly reduced the wet weight and total protein content of the sympathetic superior cervical ganglia which innervate SMG tissue. SMG-NGF and EGF concentrations were measured by specific radioimmunoassays. 6-OHDA treatment alone did not affect the basal SMG-NGF and EGF concentrations. However, the maximal responses of SMG-NGF and EGF to T4 administration were greatly reduced by concurrent treatment with 6-OHDA. In summary, the data demonstrate a critical role for developing sympathetic nervous system in the T4-stimulated increase in SMG-NGF and EGF concentrations.