Evolution of Plasma Dopamine-Beta-Hydroxylase in Hypo- and Hyperthyroid Young Rats

Immature superior cervical ganglia and brain stem pieces containing 5-hydroxytryptamine neurons of the dorsal raphe nucleus were grafted to the anterior eye chamber of intact and thyroidectomized recipients. The grafts were left in the eye to mature for 4-6 weeks and were measured through the translucent cornea repeatedly to follow survival and growth. Monoaminergic nerve fibre outgrowth from the grafts onto the host irides was evaluated with Falck-Hillarp monoamine histochemistry on iris whole mounts. Body weight and plasma concentrations of thyroid-stimulating hormone monitored the thyroid state of both experimental and control animals. Intraocular survival and growth of immature superior cervical ganglia was not influenced by thyroid hormone deficiency, whereas the size of dorsal raphe nucleus grafts significantly increased during similar conditions. This increased size was entirely counteracted by daily substitution with l-thyroxine (100 μg/kg, s.c.) to the thyroid deficient host animals. Fluorescence microscopy, including semiquantitative estimations of fibre outgrowth area and axon bundle formation in the irides, revealed no effects of the thyroid hormone deficiency on the peripheral superior cervical ganglia. The outgrowth of 5-hydroxytryptamine-containing nerve fibres from the brain stem grafts, on the other hand, showed a 50% decrease in both axon bundle formation and fibre outgrowth area in thyroidectomized hosts. This effect of the thyroidectomy could be completely reversed by daily substitution with l-thyroxine. These data strongly support earlier reports describing a thyroid hormone dependency for central noradrenaline- and dopamine-containing neurons during similar conditions. Furthermore, the results indicate a role of thyroid hormones for nerve fibre growth during development of intraocularly isolated central but not peripheral monoaminergic neurons.

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Dopamine beta‐hydroxylase and its genetic variants in human health and disease

Gonzalez-Lopez

Vrana

2019

Journal of Neurochemistry

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Dopamine beta-hydroxylase (DbH) is an essential neurotransmitter-synthesizing enzyme that catalyzes the formation of norepinephrine (NE) from dopamine and has been extensively studied since its discovery in the 1950s. NE serves as a neurotransmitter in both the central and peripheral nervous systems and is the precursor to epinephrine synthesis in the brain and adrenal medulla. Alterations in noradrenergic signaling have been linked to both central nervous system and peripheral pathologies. DbH protein, which is found in circulation, can, therefore, be evaluated as a marker of norepinephrine function in a plethora of different disorders and diseases. In many of these diseases, DbH protein availability and activity are believed to contribute to disease presentation or select symptomology and are believed to be under strong genetic control. Alteration in the DbH protein by genetic polymorphisms may result in DbH becoming ratelimiting and directly contributing to lower NE and epinephrine levels and disease. With the completion of the human genome project and the advent of next-generation sequencing, new insights have been gained into the existence of naturally occurring DbH sequencing variants (genetic polymorphisms) in disease. Also, biophysical tools coupled with genetic sequences are illuminating structure-function relationships within the enzyme. In this review, we discuss the role of genetic variants in DbH and its role in health and disease.

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Evolution of Plasma Dopamine-Beta-Hydroxylase in Hypo- and Hyperthyroid Young Rats

Cited by 3 publications

References 9 publications

Influence of thyroid hormones on rat cerebellar cell aggregation and survival in culture

Influence of thyroid hormones on rat cerebellar cell aggregation and survival in culture

Thyroid hormone dependency of the developing dorsal raphe nucleus but not the superior cervical ganglion. Evidence from intraocular grafting experiments

Dopamine beta‐hydroxylase and its genetic variants in human health and disease

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