Biomedical subjects

W T Gallucci

Publications and source records attributed to W T Gallucci.

24 records · Page 2Linked to original sources

PubMed1986

Ovine corticotropin-releasing hormone stimulation test in normal children.

We administered ovine corticotropin-releasing hormone (CRH) as a bolus iv injection (1 microgram/kg) to 21 normal boys and girls, aged 6-15 yr. CRH stimulated release of immunoreactive ACTH and cortisol in all children. The peak plasma ACTH and cortisol levels after CRH were 15.7 +/- 9.4 (SD) pg/ml and 14.3 +/- 3.6 micrograms/dl, respectively, in the girls, and 20.7 +/- 9.7 pg/ml and 16.6 +/- 3.3 micrograms/dl, respectively, in the boys. Plasma ACTH and cortisol responsiveness to CRH did not differ between girls or boys, or between children and adults. Cortisol-binding globulin concentrations in plasma did not change with age. We conclude that CRH provides a safe means of stimulating the pituitary-adrenal axis in children.

Adolescent↗

PubMed1985

Effects and pharmacokinetic properties of the rat/human corticotropin-releasing factor in rhesus monkeys.

The biological effects and pharmacokinetic properties of the recently sequenced rat/human corticotropin-releasing factor (r/hCRF) were evaluated in the rhesus monkey and compared to those of the previously studied ovine corticotropin-releasing factor (oCRF). An iv bolus of 0, 0.1, 1, 10, and 100 micrograms/kg r/hCRF and 1 microgram/kg oCRF were given to rhesus monkeys (four to five tests per dose). Serial blood samples were drawn before and up to 180 min after the injection for determination of plasma immunoreactive (IR) ACTH, cortisol, and IR-r/hCRF or IR-oCRF concentrations. Mean arterial blood pressure and heart rate were monitored. r/hCRF stimulated ACTH and cortisol secretion in a dose-dependent fashion. Its potency was similar to that of oCRF. r/hCRF, however, had a shorter half-life and a 3-fold higher MCR than oCRF. A dose-dependent decrease in the MCR of r/hCRF was observed, which may indicate a saturation of the clearance mechanisms. Significant decreases in mean arterial blood pressure, increases in heart rate, and a profound facial flush occurred at the dose of 100 micrograms/kg r/hCRF. We conclude that r/hCRF stimulates ACTH and cortisol secretion in a nonhuman primate with a potency similar to that of oCRF. The peptide has marked hypotensive effects at high doses and is cleared 3 times more rapidly than oCRF.

Adrenocorticotropic Hormone↗

PubMed1984

Human corticotropin-releasing factor in man: pharmacokinetic properties and dose-response of plasma adrenocorticotropin and cortisol secretion.

The responses of plasma immunoreactive ACTH (IR-ACTH), cortisol, GH, PRL, and LH to a single iv injection of 0.01-5 micrograms/kg human corticotropin-releasing factor (hCRF) were investigated in healthy volunteers. The lowest effective dose of hCRF was 0.5 micrograms/kg. hCRF caused brief pulse-like elevations of plasma IR-ACTH and cortisol without any effect on the plasma concentrations of GH, PRL, and LH. By contrast, ovine CRF (oCRF), given for comparison, produced long-lasting stimulation of the human pituitary-adrenal axis. The difference in duration of effect between hCRF and oCRF may be attributed to an approximately 3-4 times higher MCR of hCRF [7.9 +/- 1.2 (+/- SE) ml/kg min; n = 14] than oCRF (1.9 +/- 0.1 ml/kg min; n = 9) in man. No serious side effects occurred at any of the doses of hCRF tested. The highest dose (5 micrograms/kg) caused a slight increase of heart rate that was not associated with significant changes in arterial blood pressure. All subjects receiving 5 micrograms/kg and one third of the subjects receiving 1 micrograms/kg hCRF experienced a transient facial flush. We conclude that hCRF causes brief plasma ACTH and cortisol secretory episodes in man, similar to the physiological plasma ACTH and cortisol secretory episodes. This is in contrast to oCRF, which causes prolonged ACTH and cortisol secretion. These differences between the two peptides may be explained by the higher MCR of hCRF than oCRF.

Adrenocorticotropic Hormone↗

PubMed1984

Hemodynamic and endocrine parameters in the anesthetized cynomolgus monkey: a primate model.

Hemodynamic and endocrine parameters were determined in nine anesthetized adult male cynomolgus monkeys. Simultaneous phasic and mean pressures were measured in the right atrium, pulmonary artery, and abdominal aorta. Intermittent pulmonary artery wedge pressures and mean cardiac output measured by the thermal dilution method were used to calculate stroke volume, systemic vascular resistance, and pulmonary vascular resistance. Plasma adrenocorticotropic hormone (ACTH), cortisol, and plasma renin activity were measured throughout the procedure. Technical aspects, data in the anesthetized monkey, and comparison with previously reported data are presented.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Hemodynamic effects of corticotropin releasing hormone in the anesthetized cynomolgus monkey.

Right atrial bolus administration of rat/human corticotropin releasing hormone (r/hCRH) at a dose of 90 micrograms/kg to anesthetized cynomolgus monkeys caused a dramatic and prolonged fall in both the peripheral vascular resistance (48% reduction) and mean systemic blood pressure (36% reduction). An associated tachycardia could be blocked with prior propranolol administration and thus was probably reflexic. A mean 43 and 37% increase in the flow of the superior mesenteric and common iliac arteries, respectively, was demonstrated with electromagnetic flow probes. These changes were associated with a concomitant 38 and 40% diminution in the respective vascular resistance. Similar blood flow changes were noted in the carotid artery, however, these were of a much shorter duration. None of these changes occurred in placebo-treated animals. Plasma adrenocorticotropic hormone and cortisol concentrations were elevated basally and throughout the procedure and were similar in the experimental and control groups, suggesting maximal activity of the hypothalamic-pituitary-adrenal axis. Plasma renin activity, however, gradually increased in the r/hCRH-treated animals, probably as a result of the systemic hypotension. We speculate that CRH or a CRH-like substance may function as a paracrine hormone modulating local blood vessel tone and may be important in directing blood flow during stress and injury. The vasoactive properties of exogenous r/hCRH may be of clinical use in man.

Animals↗

PubMedDate not supplied

Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami.

Experimental evidence suggests that serotonin (5HT) is excitatory to the hypothalamic-pituitary-adrenal axis and that this effect involves activation of both hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH secretion. The present study was undertaken to examine the mechanism by which 5HT stimulates the central component of the HPA axis. To accomplish this we employed an in vitro rat hypothalamic organ culture system in which CRH secretion from single explanted hypothalami was measured by specific radioimmunoassay (IR-rCRH). All experiments were performed after an overnight (15-18 hr) preincubation. Serotonin stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped and the peak effect was observed at the concentration of 10(-9) M. The stimulatory effect of 10(-9) M 5HT was antagonized by the 5HT1 and 5HT2 receptor metergoline and by the selective 5HT2 receptor antagonists ketanserin and ritanserin. The muscarinic antagonist atropine, the nicotinic antagonist hexamethonium and the alpha-adrenergic receptor antagonist phentolamine, on the other hand, did not inhibit 5HT-induced IR-rCRH secretion. The specific 5HT2 receptor agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped with peak of effect reached at the concentration of 10(-9) M. We also tested the ability of the 5HT agonist meta-chlorophenylpiperazine (m-CPP) and of the selective 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) to cause CRH secretion. Although both m-CPP and 8-OH-DPAT stimulated IR-rCRH secretion in a dose-dependent fashion, several differences were observed when their effect was compared to that of 5HT. These included a different shape of the dose-response curve, a lower maximal stimulatory effect and a different maximal stimulatory concentration. These findings suggest that serotonin stimulates CRH secretion by explanted rat hypothalami and that this effect appears to be mediated mainly through a 5HT2 receptor mechanism.

Animals↗