Obligatory role of thyroid hormones in development of peripheral sympathetic and central nervous system catecholaminergic neurons: effects of propylthiouracil-induced hypothyroidism on transmitter levels, turnover and release.

Thyroid status is thought to play a major role in establishing the time course of development of sympathetic nerve pathways. Hypothyroidism induced by perinatal administration of propylthiouracil to developing rats resulted in substantial deficits in cardiac norepinephrine levels that persisted into adulthood. This shortfall was not accompanied by compensatory receptor supersensitivity or by increased utilization of remaining transmitter. Indeed neonatal hypothyroidism is known to result in end-organ subsensitivity and the norepinephrine turnover rate, an index of spontaneous activity of the neuron, was found to be markedly subnormal. The ability of cardiac sympathetic neurons to release transmitter upon pharmacological challenge was also compromised by hypothyroidism: in control neonates, administration of tyramine resulted in displacement of norepinephrine from nerve terminals, a response which was present very early in development. Hypothyroid rats did not develop the ability to release transmitter in response to tyramine until 10 days postnatally and a fully mature response was not apparent until weeks later. Ontogeny of the capability to release norepinephrine in response to hypotension (baroreflex) also was assessed through administration of hydralazine, a direct arteriolar vasodilator; control rats showed a characteristic development of this response at the end of the 2nd postnatal week, whereas hypothyroid rats did not show any potential for norepinephrine release until young adulthood (41 days). In comparison to cardiac sympathetic neurons, an overall evaluation of central catecholaminergic pathways in whole brain indicated a much smaller effect of hypothyroidism, with no (norepinephrine) or only minor (dopamine) deficits in transmitter content and smaller, transient reductions in turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology