Human Corticotropin-Releasing Hormone in Man: Dose-Response of Minute Ventilation and End-Tidal Partial Pressures of Carbon Dioxide and Oxygen*

The respiratory stimulant properties of iv injections of 33, 67, and 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) were studied in 12 normal men in a single blind, placebo-controlled trial. All doses of hCRH induced a respiratory stimulation in every subject, and the stimulation was dose dependent. The onset of respiratory stimulation occurred within 15-30 sec after hCRH infusion was started. Initially, there was an increase in tidal volume (VT), followed by an increase in respiratory rate. The maximum minute ventilation (VE) occurred 60-120 sec after starting the injection. The 33-micrograms hCRH dose induced a 35% increase in VE from 6.3 +/- 0.6 (+/- SD) to 9.7 +/-…

Die Messung des freien Speichel-Cortisols vor und nach intravenöser Stimulation mit Corticotropin-Releasing Hormon. Der Einfluß basaler Cortisolspiegel auf die Stimulierbarkeit.

Thyrotropin-releasing hormone has stimulatory effects on ventilation in humans

Thyrotropin-releasing hormone (TRH) stimulates pituitary thyrotropin synthesis and release and also regulates autonomic nervous system functions by acting as a neuromodulator and neurotransmitter. In experimental animals a stimulation of ventilation by thyrotropin-releasing hormone was shown when applied at central nervous system sites that affect respiratory motor output. It was the goal of our study to investigate the respiratory properties of thyrotropin-releasing hormone on basal and stimulated (i.e. CO2-rebreathing) conditions following systemic thyrotropin-releasing hormone application in healthy humans. Thyrotropin-releasing hormone (200 micrograms, 400 micrograms intravenous) initia…

Extrapituitary Effects of Corticotropin Releasing Hormone and Thyrotropin Releasing Hormone

Besides their regulation of the pituitary-adrenal and pituitary-thyroidal axis, respectively, the neurohormones CRH and TRH act within the central nervous system to evoke and modulate a number of behavioral and physiological processes. In particular, an increase in the sympathetic nervous system and respiratory activity has been observed. The data communicated in this review article emphasize the role of these neurohormones with regard to the neuroendocrine regulation of the autonomic nervous system, sleep and cognitive performance. Moreover, a possible therapeutic role is suggested by the beneficial effects in patients at risk of hypoventilation-associated disorders.

Intra- and extracerebral blood flow changes and flushing after intravenous injection of human corticotropin-releasing hormone

To study facial flush after systemic administration of human corticotropin-releasing hormone (hCRH) we injected 100 micrograms hCRH intravenously to ten healthy young men. The increase in facial temperature was measured by infrared camera. A significant increase in facial temperature of 1.39 degrees C +/- 0.3 was found within 7 min in all patients, which lasted up to 60 min, although facial flushing was visible in only 50% (5/10) of the probands. In a second experiment 100 micrograms hCRH was then administered to seven other healthy young men. Intra- and extracerebral blood flow velocity changes in the medial cerebral artery (MCA) and external carotid artery (ECA) were measured after hCRH a…

Human corticotropin-releasing hormone and thyrotropin-releasing hormone modulate the hypercapnic ventilatory response in humans

Human corticotropin-releasing hormone (hCRH) and thyrotropin-releasing hormone (TRH) are known to stimulate ventilation after i.v. administration in humans. In a placebo-controlled, single-blind study we aimed to clarify if both peptides act by altering central chemosensitivity. Two subsequent CO2-rebreathing tests were performed in healthy young volunteers. During the first test 0.9% NaCl was given i.v.; during the second test 200 micrograms of hCRH (n = 12) or 400 micrograms of TRH (n = 6) was administered i.v. Nine subjects received 0.9% NaCl i.v. during both rebreathing manoeuvres. The CO2-response curves for the two tests were compared within the same subject. In the hCRH group a marke…

Human corticotropin-releasing factor (hCRF) is a potent respiratory analeptic. Physiological and clinical aspects.

During intravenous corticotropin-releasing factor stimulation tests we observed a deepening of the tidal volume in 35 patients. To investigate this presumed respiratory stimulation we measured respiratory parameters in 12 healthy male volunteers in a single-blind placebo-controlled trial. The intravenous 60-s infusion of 100 micrograms of human corticotropin-releasing factor induced a very potent respiratory stimulation in every subject: respiratory minute volume (mean +/- S.D.) increased by 81% from 6.319 +/- 0.577 to 11.464 +/- 1.264 liters per min (P less than 0.001), whereas there was only a slight rise in the mean respiratory rate from 12.4 +/- 3.0 to 14.7 +/- 2.7 breaths per min (P le…

Respiratory Parameters after Systemic Corticotropin-Releasing Hormone Administration

Neuroanatomical studies on the distribution of corticotropin-releasing hormone (CRH) and its receptors (7) as well as physiological data suggest a regulatory function of endogenous CRH in hypothalamic and extrahypothalamic brain areas [1, 4]. Endogenous CRH acts within the endocrine hypothalamo-pituitary-adrenal axis and affects cardiovascular regulation and respiration through extrahypothalamic pathways. CRH also stimulates gluconeogenesis and release of plasma-catecholamines. Our experiments in humans also demonstrate an influence on respiration and on heart rate activity after systemic application of CRH. Respiratory parameters and heart rate were analyzed during steady-state conditions …

Safety and side effects of human and ovine corticotropin-releasing hormone administration in man.

Synthetic human and ovine corticotropin-releasing hormone (hCRH, oCRH) are commonly used as a diagnostic tool of the hypothalamo-pituitary-adrenal axis. In this paper reports about side effects after various modes of CRH-application are analyzed and compared to our corresponding data of human studies with hCRH and oCRH. Generally, CRH is well tolerated after single administration and interval-application of standard doses, although minor side effects appear sometimes after higher doses (greater than 200 micrograms hCRH, oCRH) of CRH-bolus-injections. Predominantly the cardiovascular system (e.g. tachycardia, hypotension, flushing) is affected; neuropsychological symptoms are only seen spora…

Effects of corticotropin-releasing hormone on respiratory parameters during sleep in normal men.

Corticotropin-releasing hormone (CRH) is well-known to be a centrally acting respiratory stimulant after systemic application both in healthy subjects and in patients suffering from respiratory failure. In order to study the effects of CRH on sleep EEG and respiratory parameters during sleep, 14 healthy male volunteers were investigated in a single-blind placebo controlled design. After an adaptation night, polysomnography was performed during two successive nights between 23.00 hrs. and 7.00 hrs. During one night placebo was applied, on the other 50 μg ovine CRH was administered intravenously as a bolus every hour from 0.00 hrs. to 6.00 hrs. For the assessment of respiration, blood oxygen …

Time-related effects of thyrotropin-releasing hormone (TRH) on the pituitary-thyroid axis and extrathyroidal targets.

Thyrotropin-releasing hormone (TRH) is a tripeptide and acts as a stimulator of the pituitary-thyroid axis as well as having a great number of well defined extrathyroidal functions. Studies in experimental animals have shown, that TRH also has a role as a neuromodulator within the autonomous nervous system. In this study we analyzed the effects following peripheral administration of TRH (200 micrograms, 400 micrograms) in patients with endocrinological disorders and in healthy females and males. By means of a questionnaire, patients were asked about possible (side-) effects; ventilatory and cardiovascular monitoring was performed during steady state. The pulsatile TSH-secretion pattern was …