Glucocorticoids Decrease Thyrotropin-Releasing Hormone Messenger Ribonucleic Acid Expression in the Paraventricular Nucleus of the Human Hypothalamus

Abstract

The way glucocorticoids affect TRH mRNA expression in the paraventricular nucleus of the hypothalamus is still unclear. In view of its relevance for Cushing's syndrome and depression, we measured TRH mRNA expression in human hypothalami obtained at autopsy by means of quantitative TRH mRNA in situ hybridization. In corticosteroid-treated subjects (n = 10), TRH mRNA hybridization signal was decreased as compared with matched control subjects (n = 10) (Mann-Whitney U test, P = 0.02). By inference, hypercortisolism as present in patients with Cushing's syndrome or major depression may contribute to lower serum TSH or symptoms of depression by lowering hypothalamic TRH expression.

Central neuropeptide Y infusion and melanocortin 4 receptor antagonism inhibit thyrotropic function by divergent pathways

“…Adrenalectomy in rats increases pro-TRH mRNA levels in the PVN, whereas administration of exogenous corticosterone or dexamethasone to rats has the opposite effect (Kakucska et al, 1995). Similar effects appear to be at play in humans, since people that had been treated with glucocorticoids until the time of death showed a significant decrease in TRH mRNA levels in the PVN compared to control subjects (Alkemade et al, 2005), and glucocorticoid excess suppresses the secretion of TSH in humans (Nicoloff et al, 1970). In addition to glucocorticoids, the hypothalamo-pituitary-thyroid axis is regulated by insulin.…”

“…Additionally, whereas acute or chronic ICV NPY administration induced pronounced hypercorticosteronemia and hyperinsulinemia, HS014 induced a modest rise in corticosteronemia only during the first hour after acute ICV injection. As glucocorticoids inhibit activity of the thyrotropic axis (Kakucska et al, 1995, Alkemade et al, 2005and Nicoloff et al, 1970, this finding may contribute to the observed differences in effects of NPY versus HS014 on plasma TSH and free T4 concentrations. Despite these patent dissimilarities in hormonal responses to central administration of NPY or the MC4 receptor antagonist HS014, both peptides resulted in marked and significant increases in adiposity and leptinemia after chronic infusion, even though pair feeding with vehicle-infused control animals prevented NPY-and HS014-induced hyperphagia.…”

“…Moreover, corticosterone and insulin status can have significant effects on thyroid hormone concentrations (Kakucska et al, 1995, Alkemade et al, 2005, Nicoloff et al, 1970, Gonzalez et al, 1980and Mitsuma and Nogimori, 1982. Therefore, in order to determine whether changes in insulin or corticosterone levels may have contributed to these changes in thyroid hormone concentrations, we investigated circulating insulin and corticosterone concentrations in NPYand HS014-injected rats.…”

“…Acute ICV NPY administration is known to modulate circulating concentrations of corticosterone and insulin (Sainsbury et al, 1996;Wisialowski et al, 2000), both of which -in addition to thyroid hormones -influence energy homoestasis. Moreover, corticosterone and insulin status can have significant effects on thyroid hormone concentrations (Kakucska et al, 1995;Alkemade et al, 2005;Nicoloff et al, 1970;Gonzalez et al, 1980;Mitsuma and Nogimori, 1982). Therefore, in order to determine whether changes in insulin or corticosterone levels may have contributed to these changes in thyroid hormone concentrations, we investigated circulating insulin and corticosterone concentrations in NPY-and uncoupling protein 3 (UCP-3) in this tissue was determined, since the expression and activity of UCP-3 is known to be regulated by thyroid function (Lanni et al, 2003;Flandin et al, 2009).…”

Thyroid hormone transporters and deiodinases in the developing human hypothalamus

“…Preterm children therefore suffer from transient hypothyroxinemia, which may affect hypothalamic TH signaling (30,31,32). In addition, we cannot exclude effects of non-thyroidal illness or glucocorticoid treatment on protein expression levels (33,34). Strikingly, toward the end of gestation, TH transporters and D2 immunoreactivity decreased, whereas D3 expression increased.…”