Thyroid hormone control of preganglionic innervation of the adrenal medulla and chromaffin cell development in the rat. An ultrastructural, morphometric and biochemical evaluation.
In the rat, functional connections between the splanchnic nerve and the adrenal medulla are immature at birth and do not become fully competent until the first postnatal week. Neonatal administration of triiodothyronine (T3) accelerates this process, and the present study was undertaken to elucidate the underlying mechanisms. Rats were given T3 (0.1 mg/kg, s.c.) daily for 9 days beginning 1 day after birth. Preganglionic innervation of the adrenal medulla was examined by retrograde axonal transport of horseradish peroxidase (HRP). At 10 days of age, there was an increased number of labeled perikarya in the spinal cord of the hyperthyroid pups. Ultrastructural examination revealed a corresponding increase in synaptic density in the adrenal medulla and in the activity of choline acetyltransferase, a marker for preganglionic cholinergic nerve terminals. These effects were attenuated by 25 days of age, whereupon deficits in HRP-labeled neurons and adrenomedullary synapses were noted. Similarly, replication of chromaffin cells was enhanced transiently in the T3 group during the initial stage of hyperthyroidism, but subsequent long-lasting deficits in cell numbers were noted, along with a corresponding retardation of ontogeny of adrenal catecholamine biosynthesis and storage. Thus, neonatal hyperthyroidism accelerates synaptic development in the sympatho-adrenal axis but suppresses maturation of the target chromaffin cells, ultimately leading to impaired adrenomedullary function.
Lau
C
C
Northrop Services, Inc., Environmental Sciences, Research Triangle Park, NC 27709.
Franklin
M
M
McCarthy
L
L
Pylypiw
A
A
Ross
L L
LL
D000313:Adrenal Medulla / Q000166:cytology / Q000254:growth & development / Q000294:innervation*; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001370:Axonal Transport; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D006735:Horseradish Peroxidase; D008940:Mitotic Index; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013116:Spinal Cord / Q000254:growth & development; D013153:Splanchnic Nerves / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D013936:Thymidine / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014909:Wheat Germ Agglutinins
D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; D014909:Wheat Germ Agglutinins; D014284:Triiodothyronine; D006735:Horseradish Peroxidase; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D013936:Thymidine