Effects of corticotropin-releasing hormone on gastric electrical activity and sensorimotor function in healthy volunteers: a double-blinded crossover study.

Biopsychosocial factors are associated with disorders of gut-brain interaction (DGBI) and exacerbate gastrointestinal symptoms. The mechanisms underlying pathophysiological alterations of stress remain unclear. Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response and has diverse impact on different organ systems. The aim of the present study was to investigate the effects of peripheral CRH infusion on meal-related gastrointestinal symptoms, gastric electrical activity, and gastric sensorimotor function in healthy volunteers (HVs). In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effects of CRH on gastric motility and sensitivity. HVs were randomized to receive either peripheral-administered CRH (100 µg bolus + 1 µg/kg/h) or placebo (saline), followed by at least a 7-day washout period and assignment to the opposite treatment. Tests encompassed saliva samples, gastric-emptying (GE) testing, body surface gastric mapping (BSGM, Gastric Alimetry; Alimetry) to assess gastric myoelectrical activity with real-time symptom profiling, and a gastric barostat study to assess gastric sensitivity to distention and accommodation. Twenty HVs [13 women, mean age 29.2 ± 5.3 yr, body mass index (BMI) 23.3 ± 3.8 kg/m2] completed GE tests, of which 18 also underwent BSGM measurements during the GE tests. The GE half-time decreased significantly after CRH exposure (65.2 ± 17.4 vs. 78.8 ± 24.5 min, P = 0.02) with significantly increased gastric amplitude [49.7 (34.7-55.6) vs. 31.7 (25.7-51.0) µV, P < 0.01], saliva cortisol levels, and postprandial symptom severity. Eleven HVs also underwent gastric barostat studies on a separate day. However, the thresholds for discomfort during isobaric distensions, gastric compliance, and accommodation did not differ between CRH and placebo.NEW & NOTEWORTHY In healthy volunteers, peripheral corticotropin-releasing hormone (CRH) infusion accelerates gastric-emptying rate and increases postprandial gastric response, accompanied by a rise in symptoms, but does not alter gastric sensitivity or meal-induced accommodation. These findings underscore a significant link between stress and dyspeptic symptoms, with CRH playing a pivotal role in mediating these effects.

Alterations in hippocampal cholinergic dynamics following CRF infusions into the medial septum of male and female rats.

Corticoptropin releasing factor (CRF) is implicated in stress-related physiological and behavioral changes. The septohippocampal pathway regulates hippocampal-dependent mnemonic processes, which are affected in stress-related disorders, and given the abundance of CRF receptors in the medial septum (MS), this pathway is influenced by CRF. Moreover, there are sex differences in the MS sensitivity to CRF and its impact on hippocampal function. However, the mechanisms underlying these associations remain elusive. In the present study, we utilized an in vivo biosensor-based electrochemistry approach to examine the impact of MS CRF infusions on hippocampal cholinergic signaling dynamics in male and female rats. Our results show increased amplitudes of depolarization-evoked phasic cholinergic signals in the hippocampus following MS infusion of CRF at the 3 ng dose as compared to the infusion involving artificial cerebrospinal fluid (aCSF). Moreover, a trend for a sex × infusion interaction indicated larger cholinergic transients in females. On the contrary, intraseptal infusion of a physiologically high dose (100 ng) of CRF produced a subsequent reduction in phasic cholinergic transients in both males and females. The assessment of tonic cholinergic activity over 30 min post-infusion revealed no changes at the 3 ng CRF dose in either sex, but a significant infusion × sex interaction indicated a reduction in females at the 100 ng dose of CRF as compared to the aCSF. Taken together, our results show differential, dose-dependent modulatory effects of MS CRF on the dynamics of phasic and tonic modes of cholinergic signaling in the hippocampus of male and female rats. These cholinergic signaling modes are critical for memory encoding and maintaining arousal states, and may underlie sex differences in cognitive vulnerability to stress and stress-related psychiatric disorders.

Teste do fator liberador de corticotrofina (hCRF) em indivíduos normais / Corticotropin-releasing factor stimulation test (ACTH) in normal subjects

Em sete indivíduos normais foram estudadas as respostas do ACTH e cortisol plasmáticos ao fator liberador de corticotrofina (hCRF sintético 1 microng/Kg de peso), aplicado em bolus endovenoso às 9:00h. Como controle foi infundido soro fisiológico em quatro indivíduos. O hCRF determinou acréscimos significativos dos níveis plasmáticos de ACTH e cortisol, sendo as respostas máximas em média aos 30 e 60 minutos, respectivamente. O acréscimo percentual máximo foi de 85,7% para o ACTH e 91,4% para o cortisol. Os picos máximos de ACTH näo ultrapassaram o limite superior (50 pg/ml) obtido às 9:00h em condiçöes basais no nosso laboratório, sugerindo que o estímulo com esta dose de hCRF sintético mimetizaría a secreçäo pulsátil de ACTH decorrente dos pulsos espontâneos de CRF endógeno. Cinco indivíduos tiveram sensaçäo de calor na face e flushing imediatamente após a injeçäo do hCRF. A näo ocorrência de outros efeitos colaterais é indicativa que esta dose de hCRF é segura. Assim sendo, descrevemos nossa experiência pioneira no país com o teste do hCRF, o qual pode ser usado no estudo da fisiologia humana e no arsenal diagnóstico de doenças do eixo hipotálamo-hipófise-adrenais

Distinct grooming patterns induced by intracerebroventricular injection of CRH, TRH and LHRH in male rats

This paper reports the effects on grooming, related behaviors and levels of anxiety induced by the hypophysiotropic peptides corticotropin-releasing hormone (CRH, 1 mug, 0.2 nmol, icv), thyrotropin-releasing hormone (TRH, 100 mug, 275 nmol, icv) and luteinizing hormone-releasing hormone (LHRH, 1.5 mug, 1.3 nmol, icv) administered into the lateral ventricle of the brain (icv) of adult male rats of a Holtzman-derived colony (N = 15, each group). CRH induced an increase in total grooming scores, whereas LHRH, TRH and vehicle had no effect. CRH strongly increased face and head grooming and induced head shakes. The time spent in rearing and gnawing was significantly decreased. In the plus-maze, CRH reduced the time of exploration in the open arm. TRH increased face grooming and induced body shakes. LHRH had no effect on grooming or rearing behavior. No body or head shakes were observed after LHRH administration. Scoring of individual grooming elements demonstrated differences in action of the three peptides. Although both CRH and TRH increased face grooming, only CRH induced head grooming. Furthermore, CRH induced predominantly head shakes while TRH increased body shake activity. In contrast, CRH was anxiogenic and TRH appeared to induce stereotyped behavior. From the characterization of grooming elements and related responses, we conclude that each hypophysiotropic peptide induces a specific behavioral pattern.