S. L. Jeffcoate

Distribution of thyroptropin-releasing hormone (TRH) in the central nervous system as revealed with immunohistochemistry

With the indirect immunofluorescence technique TRH-containing nerve terminals were found in the medial part of the external layer of the median eminence, the dorsomedial nucleus and the perifornical area, in extrahypothalmic nuclei such as nucleus accumbens, the lateral septal nucleus and in several motor nuclei of the brain stem and spinal cord. These findings suggest that TRH may act both as a hormone, released into the portal vessels, as well as a neurotransmitter or modulator, released at synapses in discrete regions of the brain and spinal cord.

Thyrotropin releasing hormone (TRH)-containing nerve terminals in certain brain stem nuclei and in the spinal cord

With the indirect immunofluorescence technique the localization of thyrotropin releasing hormone (TRH) has been studied in the lower brain stem and spinal cord. Networks of TRH-positive nerve terminals were observed in many cranial nerve cell nuclei and around the motoneurons in the spinal cord.

Ultrastructural localization of TRH-like immunoreactivity

SummaryWith the peroxidase-antiperoxidase (PAP) method TRH-like immunoreactivity (TRH-LI) was observed in certain neurons of the central nervous system. Their distribution agreed well with findings previously obtained with the indirect immunofluorescence technique. At the ultrastructural level electron-dense precipitates representing TRH-LI were observed in so-called large dense core vesicles, which were localized both in the cytoplasm of some hypothalamic neuronal cell bodies, as well as in boutons in the hypothalamus and spinal cord. The boutons often seemed to form axo-somatic or axodendritic synapses.

THE INACTIVATION OF THYROTROPHIN RELEASING HORMONE BY PLASMA IN THYROID DISEASE

The inactivation of immunoreactive TRH in vitro by human plasma has been investigated. In a preliminary study, 2.5 ng TRH was destroyed by 50 μl plasma at a mean rate of 1.7%/min in eight subjects. The per cent inactivation of the same amount of TRH at three plasma dose levels was measured after 60 min in seventy unselected patients attending a thyroid clinic. There was no significant difference in the results obtained in those subsequently shown to be euthyroid (forty‐three patients), hyperthyroid (eighteen patients) or hypothyroid (nine subjects).

CLEARANCE AND IDENTIFICATION OF THYROTROPHIN RELEASING HORMONE IN HUMAN URINE AFTER INTRAVENOUS INJECTIONS

The urine clearance of TRH after intravenous injection in man has been measured by radioimmunoassay. Between 4.4% and 10.7% of the dose was excreted within 90 min, the majority within 30 min. The TRH excreted was immunochemically and chromatographically indistiguishable from synthetic TRH and was inactivated by plasma enzymes with the same kinetic characteristics. The immunoreactive TRH‐like material in basal urine samples was not TRH however: chromato‐graphically and enzymatically it behaved differently from the synthetic tripeptide.

Age-dependent changes in the inactivation of thyrotrophin-releasing hormone by different areas of rat brain

Age-dependent changes in the inactivation of thyrotrophin-releasing hormone (TRH) were investigated in two subcellular fractions prepared from hypothalamus, thalamus, cortex and cerebellum of male rats. It was found that, in both supernatant and particulate fractions from the four brain areas, enzyme activity increased to a peak at 10-25 days of age and then decreased gradually until adult levels were reached. The changes in TRH degradation observed may be related to alterations in hypothalamic TRH content with age and to maturation of the tripeptides putative neurotransmitter/neuromodulator function.

Degradation of thyrotrophin-releasing hormone in subcellular fractions from different areas of the rat central nervous system.

Abstract Peptidases inactivating thyrotrophin-releasing hormone (TRH) were found to be present in two subcellular fractions prepared from the hypothalamus, thalamus, cortex and cerebellum of male rats, with the highest enzyme activity being detected in the cortex. TRH immunoreactivity was also measured in the two fractions from the 4 brain areas, after peptidase activity had first been removed by heat denaturation: the particulate fraction had a significantly higher TRH content than the supernatant fraction; of the regions investigated, the hypothalamus had the highest content, although TRH was detected in all the 4 brain regions. These findings provide further evidence that TRH may be one of several brain peptides having either a neuro transmitter function of a role as modulators of neuronal activity.

Local degradation of luteinizing hormone-releasing hormone (LH-RH) in the rat central nervous system

Peptidases inactivating luteinizing hormone-releasing hormone (LH-RH) were found to be present in two subcellular fractions prepared from the following areas of the central nervous system of male and female rats: thalamus, hypothalamus, cortex and cerebellum. LH-RH immunoreactivity was also detected in these fractions after peptidase activity had been removed by heat denaturation. These findings support the concept that LH-RH may have a role in modulating neuronal activity within the central nervous system (CNS).