Central nervous system effects of thyrotropin-releasing hormone and its analogues: opportunities and perspectives for drug discovery and development

Prókai, László

doi:10.1007/978-3-0348-8171-5_5

Cited by 30 publications

(33 citation statements)

References 185 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, the current options for treatment of narcolepsy include CNS stimulants for EDS and antidepressants for cataplexy (41). TRH receptors are distributed widely in the CNS (15), and TRH has diverse neuromodulating actions (15,48). Among many other features, it has CNS-stimulant and -antidepressant effects (18,29).…”

Section: Discussionmentioning

confidence: 99%

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men

Kok

Roelfsema

Overeem

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. Injection of hypocretin-1 acutely suppresses TRH and TSH release in rats. In contrast, subchronic administration does not appear to affect the hypothalamo-pituitary-thyroid ensemble in animals. We explored (in 7 patients and 7 controls) whether hypocretin deficiency impacts circulating TSH levels and circadian timing of TSH release in narcoleptic humans. Plasma TSH concentration profiles (blood samples taken at 10-min intervals during 24 h) and TSH levels in response to TRH injection were analyzed by Cluster, robust regression, approximate entropy (ApEn), and deconvolution. Circulating TSH levels were lower in patients, which was primarily attributable to lower pulse amplitude and nadir concentrations. TSH secretion correlated positively with mean 24-h leptin levels (R 2 ϭ 0.46, P ϭ 0.02) and negatively with amount of sleep (R 2 ϭ 0.29, P ϭ 0.048). Patternsynchrony between 24-h leptin and TSH concentrations was demonstrated by significant cross-correlation and cross-ApEn analyses with no differences between controls and patients. Sleep onset was closely associated with a fall in circulating TSH. Features of diurnal rhythmicity of circulating TSH fluctuations were similar in patients and controls, with the acrophase occurring shortly after midnight. Thyroxine and triiodothyronine concentrations were similar in patients and controls and did not display a diurnal rhythm. The response of plasma TSH levels to TRH was also similar in both groups. Sleep patterns in narcoleptics were significantly disorderly compared with controls, as measured by ApEn (P ϭ 0.006). In summary, circulating TSH concentrations are low in hypocretin-deficient narcoleptic men, which could be attributable to their low plasma leptin levels and/or their abnormal sleep-wake cycle.narcolepsy; thyroid-stimulating hormone; orexin; sleep; entropy NARCOLEPSY IS A NEUROLOGICAL DISORDER, characterized by excessive daytime sleepiness (EDS), hypnagogic hallucinations, cataplexy, and sleep paralysis (41), which affects 20 -60 of every 100,000 subjects in the US and Europe (32). Disruption of hypocretin (orexin) neurotransmission underlies the disease in animals and humans (28,39). Hypocretins (hypocretin-1 and -2, also called orexin A and B) are produced by a small group of neurons in the lateral hypothalamus, which project widely throughout the central nervous system (CNS) (8, 56). The paraventricular nucleus (PVN) is among the various brain sites that receive hypocretin input signals (7). This nucleus harbors neurons that synthesize thyrotropin-releasing hormone (TRH), which is involved in the regulation of the hypothalamo-pituitary-thyroid (HPT) axis (24). During starvation, thyroid hormone secretion is suppressed (2, 52), whereas preprohypocretin mRNA is upregulated in the lateral hypothalamus (4). This led us to hypothesize that hypocretin neural circuits can modulate the activity of hypothalamic TRH neurons and thereby impact the HPT axis.Studies of the puta...

show abstract

Section: Discussionmentioning

confidence: 99%

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men

Kok

Roelfsema

Overeem

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Synthesis of TRH is reduced only in the FFR rats, while it increases after 7 days of DIA. LHA TRHergic cells send projections to the septum, an area involved in arousal (Ishikawa et al, 1986;Prokai, 2002), thus, it is not unlikely that the peptide synthesized in LHA has functions related to maintain an alertness state in food restricted animals.…”

Section: Tshmentioning

confidence: 99%

Differential Adaptations of the Hypothalamus-Pituitary-Thyroid Axis Between Food Restriction and Anorexia

Gortari¹,

Alvarez-Salas²,

Morales-Mulia³

et al. 2012

Hypothyroidism - Influences and Treatments

View full text Add to dashboard Cite

“…The highdosage regimes thus needed to obtain neuropharmacological effects often result in adverse side effects arising from the endocrine actions of TRH. Although, analogs with potent CNS activity have been synthesized, none is devoid of endocrine TSHreleasing and other nonendocrine CNS side effects [9].…”

Section: Introductionmentioning

confidence: 99%

Selectivity-based QSAR approach for screening and evaluation of TRH analogs for TRH-R1 and TRH-R2 receptors subtypes

Kadam

Chavan

Monga

et al. 2008

Journal of Molecular Graphics and Modelling

View full text Add to dashboard Cite

Central nervous system effects of thyrotropin-releasing hormone and its analogues: opportunities and perspectives for drug discovery and development

Cited by 30 publications

References 185 publications

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men

Altered setting of the pituitary-thyroid ensemble in hypocretin-deficient narcoleptic men

Differential Adaptations of the Hypothalamus-Pituitary-Thyroid Axis Between Food Restriction and Anorexia

Selectivity-based QSAR approach for screening and evaluation of TRH analogs for TRH-R1 and TRH-R2 receptors subtypes

Contact Info

Product

Resources

About