Individual Differences in the Expression of Tyrosine Hydroxylase mRNA in Neurosecretory Neurons of the Human Paraventricular and Supraoptic Nuclei: Positive Correlation with Vasopressin mRNA

Abstract

Previous studies indicated that in the human paraventricular nucleus (PVN) and in the supraoptic nucleus (SON) tyrosine hydroxylase (TH) – the first and rate-limiting enzyme in catecholamine synthesis – is localized mainly in magnocellular neurosecretory neurons. Individual differences were observed among control subjects in number and distribution of TH-immunoreactive (IR) perikarya, indicating that antemortem factors may regulate TH expression. Since a large number of TH-IR perikarya were observed in subjects who suffered from somatic illnesses leading to prolonged osmotic or nonosmotic stimulation of vasopressin (VP) release, we suggested that TH expression is related to the activation of VP neurons. The purpose of our study was to apply (1) in situ hybridization for TH mRNA on human PVN and SON to investigate how the previously reported individual differences in TH protein expression are depicted at the transcriptional level and (2) quantitative TH immunohistochemistry and in situ hybridization for VP mRNA throughout the dorsolateral part of the SON (dl-SON) in order to elucidate whether indeed expression of TH in neurosecretory nuclei depends on activation of VP neurons. Postmortem formalin-fixed, paraffin-embedded hypothalamic sections of 16 control subjects were studied for TH protein and TH and VP mRNAs. For 6 of the above cases, the number of TH-IR neurons and the total VP mRNA levels were estimated throughout the entire dl-SON using an image analysis system. Individual variation was observed in TH mRNA expression which appears to parallel the expression of TH-protein. Using Spearman’s bivariate test, a positive correlation was found between the number of TH-IR- and TH-mRNA-expressing neurons in both PVN and SON (p < 0.01) as well as between the number of TH-IR neurons and the total VP mRNA in the dl-SON (p < 0.05). Our results show (1) that the individual variability in the number of TH-IR neurons within the neurosecretory nuclei might be due to differential expression and/or stability of TH mRNA and (2) that expression of TH-immunoreactivity in human PVN and SON depends on the activation of VP neurons.

Stress Stimulates Production of Catecholamines in Rat Adipocytes

“…Moreover, discrepancy between TH mRNA and protein level might appear also due to different stability, transcription rate, post-transcriptional modifications by RNA interference or epigenetic regulation of TH and PNMT expression in adipocytes during various time intervals of stress exposure, similarly as described in other cells and tissues (Lenartowski and Goc, 2011; Nakashima et al, 2007; Panayotacopoulou et al, 2005). …”

Vasopressinergic neurons of the supraoptic nucleus in perinatal rats: reaction to osmotic stimulation and its regulation

“…Co-expression of tyrosine hydroxylase (TH), the first rate-limiting enzyme of catecholamine synthesis, under functional stimulation or deafferentation of VP neurons, appears to be among the most intriguing observations (Kiss and Mezey 1986;Abramova et al 2000Abramova et al , 2002Panayotacopoulou et al 2005). TH, as Fos (Pirnik and Kiss 2005), is considered as a marker of the VP neuron activation and plasticity, although the functional role and regulation of TH remain uncertain (Marsais and Calas 1999;Kontostavlaki et al 2006).…”

Expression of vasopressin mRNA in the hypothalamus of individuals with a diagnosis of schizophrenia

“…Thus, in the above quoted study by Mai et al (), these authors did not find a reduction in neurophysin staining in the supraoptic nucleus of the schizophrenic patients compared to controls. Further, in a combined immunohistochemical and in situ hybridization study of vasopressin in the supraoptic nucleus, it was not possible to detect any difference in vasopressin expression and vasopressin mRNA expression in this nucleus in schizophrenic patients compared to controls (Panayotacopoulou, Malidelis, Heerikhuize, Unmehopa, & Swaab, ).…”

“…This problem has also been investigated in human postmortem hypothalamus. Thus, a combined immunohistochemical and in situ hybridization study showed that the number of cell bodies immunoreactive to tyrosine hydroxylase, the rate‐limiting enzyme in the catecholamine synthesis, and mRNA encoding tyrosine hydroxylase was well correlated (Panayotacopoulou et al, ). We have in our material of the brains of deceased with schizophrenia investigated the expression of proteins by use of antibodies against both vasopressin and neurophysin.…”