TRH
Pro-thyrotropin-releasing hormone precursor (Pro-TRH) (Prothyroliberin) [Contains: Thyrotropin-releasing hormone (TRH) (Protirelin) (TSH-releasing factor) (Thyroliberin) (Thyrotropin-releasing factor) (TRF)]
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Bisphenol A (BPA) is a component of polycarbonate plastics, epoxy resins and polystyrene found in many common products. Several reports revealed potent in vivo and in vitro effects. In this study we analyzed the effects of the exposure to BPA in the hypothalamic-pituitary-thyroid axis in female rats, both in vivo and in vitro. Female Sprague-Dawley rats were injected sc from postnatal day 1 (PND1) to PND10 with BPA: 500 μg 50 μl oil (B500), or 50 μg 50 μl (B50), or 5 μg 50 μl (B5). Controls were injected with 50 μl vehicle during the same period. Neonatal exposure to BPA did not modify TSH levels in PND13 females, but it increased them in adults in estrus. Serum T4 was lower in B5 and B500 with regards to Control, whereas no difference was seen in T3. No significant differences were observed in TRH, TSHβ and TRH receptor expression between groups. TSH release from PPC obtained from adults in estrus was also higher in B50 with regard to Control. In vitro 24 h pre-treatment with BPA or E increased basal TSH as well as prolactin release. On the other hand, both BPA and E lowered the response to TRH. The results presented here show that the neonatal exposure to BPA alters the hypothalamic pituitary-thyroid axis in adult rats in estrus, possibly with effects on the pituitary and thyroid. They also show that BPA alters TSH release from rat PPC through direct actions on the pituitary.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Benzhydryl Compounds
- Cells, Cultured
- Dose-Response Relationship, Drug
- Endocrine Disruptors
- Female
- Hypothalamus
- Phenols
- Pituitary Gland
- Rats, Sprague-Dawley
- Receptors, Thyrotropin-Releasing Hormone
- Thyroid Gland
- Thyrotropin
- Thyrotropin-Releasing Hormone
Keywords
- Bisphenol A
- Prolactin
- Thyroid hormone
- Thyrotrope
- Thyrotropin
Diagnosis of equine pituitary pars intermedia dysfunction (PPID) remains a challenge as multiple factors (stress, exercise, and time of year) influence ACTH and cortisol concentrations. To assess endocrine status in a study designed to evaluate the effects of age and diet on glucose and insulin dynamics, we performed thyrotropin-releasing hormone (TRH) stimulation tests and overnight dexamethasone suppression tests in March, May, August, and October on 16 healthy Thoroughbred and Standardbred mares and geldings. Horses were grouped by age: adult (mean ± SD; 8.8 ± 2.9 yr; n = 8) and aged (20.6 ± 2.1 yr; n = 8). None of the horses showed clinical signs (hypertrichosis, regional adiposity, skeletal muscle atrophy, lethargy) of pituitary pars intermedia dysfunction. Horses were randomly assigned to groups of 4, blocked for age, and fed grass hay plus 4 isocaloric concentrate diets (control, starch-rich, fiber-rich, and sugar-rich) using a balanced Latin square design. Data were analyzed using a multivariable linear mixed regression model. Baseline ACTH was significantly higher in aged horses (mean ± standard error of the mean; 60.0 ± 10.7 pg/mL) adapted to the starch-rich diet compared to adult horses (15.7 ± 12.0 pg/mL) on the same diet (P = 0.017). After controlling for age and diet, baseline ACTH concentrations were significantly increased in October (57.7 ± 7.1 pg/mL) compared to March (13.2 ± 7.1 pg/mL; P < 0.001), May (12.4 ± 7.1 pg/mL; P < 0.001), and August (24.2 ± 7.1 pg/mL; P < 0.001), whereas post-TRH ACTH was higher in August (376.6 ± 57.6 pg/mL) and October (370.9 ± 57.5 pg/mL) compared to March (101.9 ± 57.3 pg/mL; P < 0.001) and May (74.5 ± 57.1 pg/mL; P < 0.001). Aged horses had significantly higher post-dexamethasone cortisol on the starch-rich diet (0.6 ± 0.1 μg/dL) compared to the sugar-rich diet (0.2 ± 0.1 μg/dL; P = 0.021). Post-dexamethasone cortisol was significantly higher in October (0.6 ± 0.1 μg/dL) compared to March (0.3 ± 0.1 μg/dL; P = 0.005), May (0.2 ± 0.1 μg/dL; P < 0.001), and August (0.3 ± 0.1 μg/dL; P = 0.004). Breed did not influence ACTH or cortisol measurements. In conclusion, in addition to age and time of year, diet is a potential confounder as animals on a starch-rich diet may be incorrectly diagnosed with pituitary pars intermedia dysfunction.
MeSH Terms
- Adrenocorticotropic Hormone
- Aging
- Animal Feed
- Animals
- Diet
- Dietary Carbohydrates
- Female
- Horses
- Hydrocortisone
- Male
- Pituitary Gland, Intermediate
- Seasons
Keywords
- Adrenocorticotropic hormone (ACTH)
- Horse
- Nutrition
- Pituitary pars intermedia dysfunction (PPID)
- Season
- Thyrotropin-releasing hormone (TRH)
Thyrotropin releasing hormone (TRH) is primarily known as the central regulator of the hypothalamic-pituitary-thyroid (HPT) axis. However, TRH also exerts a variety of central nervous system effects independent from its activity in the HPT axis. With advancing age, decreases in TRH synthesis, expression, and activity have been demonstrated. Associated with this emerging evidence suggests that TRH is implicated in neurodegenerative diseases of aging, including Alzheimer's disease and Parkinson's disease. TRH and its synthetic analogs have been recognized as trophic factors in neurons of the diencephalon and spinal cord, and as neuroprotectants against oxidative stress, glutamate toxicity, caspase-induced cell death, DNA fragmentation, and inflammation. In this review, we will provide an overview of some of the roles of TRH, outside of the HPT axis, associated with pathological aging and neurodegeneration and we shall discuss the potential of TRH and TRH analogs for the treatment of neurodegenerative diseases.
Keywords
- Aging
- Alzheimer’s Disease
- Neuroprotection
- Parkinson’s Disease
- Thyrotropin Releasing Hormone
Thyrotropin-releasing hormone (TRH) aroused our interest when we were engaged in related experiments, so we decided to study its effects on organs, tissues, and aging-related metabolic and hormonal markers when administered in acute or chronic (oral) doses at various time points in its cyclic circadian pattern. We also wanted to determine what effects, if any, it had on aging processes in two essential systems, namely gonadal-reproductive and kidney-urinary. Our results show positive changes as a result of short-term acute and long-term chronic oral administration of TRH to old mice that included rapid correction to more juvenile levels of most typical aging-related hormonal and metabolic measurements. Remarkably, testes function was maintained by means of a 4-month oral treatment with TRH in aging mice. As we suspected upon seeing a significant increase in testes weight, TRH resulted in maintenance or even reconstitution of testes structure and function when administered in the drinking water. This was demonstrated by the active formation and proliferation of mature spermatogonia and the intensive spermatogenesis in the follicles. The same TRH treatment led to protection for the kidneys from amyloid and hyalin infiltration of tubuli and glomeruli, which typically occurs in aging mice. In fact, we observed massive deposits of amyloid and hyalin material infiltrating the shrunken glomeruli and negatively affecting filtration capacity of the untreated mice, whereas this was barely present in the TRH-treated mice. Advanced hyalin degeneration could also be observed in the tubular vessels of the untreated control mice. These experiments with TRH supplementation show clear aging-delaying and apparently even aging-reversing effects of the neuropeptide, whether it was administered parenterally or orally. TRH, like melatonin, is an anti-aging agent with a broad spectrum of activities that, because of their actions, suggest that TRH has a fundamental role in the regulation of metabolic and hormonal functions.
MeSH Terms
- Administration, Oral
- Aging
- Animals
- Female
- Kidney
- Lipid Metabolism
- Longevity
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Reproduction
- Spermatogenesis
- Testis
- Thyrotropin-Releasing Hormone
- Urinary Tract Physiological Phenomena
Aging and aging related illnesses such as cancer have been associated with inflammatory changes. Cancer-related behavioral comorbidities such as fatigue, sleep disturbances, depression have also been associated with inflammation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and other neuroendocrine changes. From a clinical perspective, cancer-related fatigue demonstrates striking similarities with the cytokine-induced sickness phenomenon in animal models. Thyrotopin-releasing hormone (TRH) plays a homeostatic role in its interaction with several biological systems, including a critical role in its interactions with the immune system. Considerable evidence supports a pivotal role for TRH in the inflammatory processes with specific relevance to the "cytokine-induced sickness behavior" paradigm. Additionally, TRH exerts arousing and analeptic effects in instances of behavioral depression. In a small proof-of-concept study conducted by our group, we investigated TRH administration as a treatment fatigue in cancer survivors in comparison with saline administration using a double-blind, crossover design. We also evaluated impact of TRH/saline administration on the inflammatory markers in these patients. TRH administration was associated with significant improvement (p < 0.05) in fatigue levels as measured by the Visual Analog Scale-Energy (VAS-E), was associated with significant (p < 0.05) improvement in sleep disturbances and improved quality of life. Notably, TRH administration was associated with decrease in C-reactive protein (CRP) levels, a marker of inflammation. This decrease in CRP level with TRH administration was associated with improvement in energy levels as measured by the VAS-E. The present review supports potential utility of TRH-based therapeutics in medical and psychiatric disorders with underlying inflammatory processes.
MeSH Terms
- Age Factors
- Aging
- Anti-Inflammatory Agents
- Comorbidity
- Controlled Clinical Trials as Topic
- Cross-Over Studies
- Double-Blind Method
- Fatigue
- Homeostasis
- Humans
- Inflammation
- Inflammation Mediators
- Neoplasms
- Quality of Life
- Sleep Wake Disorders
- Thyrotropin-Releasing Hormone
- Treatment Outcome