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Biomedical subjects

W Vale

Publications and source records attributed to W Vale.

At least 325 records · Page 18Linked to original sources
PubMed1984

Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF).

The acute i.p. administration of alcohol (EtOH) to freely moving, nonanesthetized rats caused dose-related elevations in plasma adrenocorticotropin (ACTH) and corticosterone levels. In vivo, injection of anticorticotropin-releasing factor (CRF) serum (i.v.) totally abolished this stimulatory effect, suggesting that the induction of CRF secretion by EtOH represents an essential modulator of its ability to release ACTH. Exposure to high levels of alcohol vapors for 7 days was accompanied by a decrease in hypothalamic CRF content. The acute exposure of cultured pituitary cells to 0.2% EtOH did not modify basal or CRF-induced ACTH release, whereas pretreatment of the cells with EtOH for 24 hr resulted in a marked decrease in both spontaneous and stimulated ACTH secretion. It is therefore possible that the long-term exposure to alcohol may result in an increase of CRF release by the median eminence, as well as in some loss of pituitary responsiveness. From these data, we hypothesize that the acute EtOH-induced activation of the hypothalamic-pituitary-adrenal axis probably takes place at the level of CRF-secreting neurons and that this effect may play a role in the disturbance of ACTH and corticosteroid secretion observed during chronic exposure to alcohol.

Adrenocorticotropic Hormone↗
PubMed1983

Effect of the serotonin reuptake inhibitor fluoxetine on corticotropin-releasing factor and vasopressin secretion into hypophysial portal blood.

The relative role of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in mediating serotonin-induced ACTH secretion was studied using the serotonin reuptake inhibitor fluoxetine. Fluoxetine caused a significant increase in ACTH and AVP concentrations in peripheral plasma as well as a significant increase in CRF and AVP concentrations in hypophysial portal plasma. The data suggest that increased secretion of ACTH induced by fluoxetine is mediated, at least in part, by an increase in the hypothalamic secretion of both CRF and AVP.

Adrenocorticotropic Hormone↗
PubMed1983

Inhibition of gastric acid secretion in rats by intracerebral injection of corticotropin-releasing factor.

Intracisternal injection of ovine corticotropin-releasing factor (CRF) into the pylorus-ligated rat or the rat with gastric fistula resulted in a dose-dependent inhibition of gastric secretion stimulated with pentagastrin or thyrotropin-releasing hormone. When injected into the lateral hypothalamus--but not when injected into the cerebral cortex--CRF suppressed pentagastrin-stimulated acid secretion. The inhibitory effect of CRF was blocked by vagotomy and adrenalectomy but not by hypophysectomy or naloxone treatment. These results indicate that CRF acts within the brain to inhibit gastric acid secretion through vagal and adrenal mechanisms and not through hypophysiotropic effects.

Adrenalectomy↗
PubMed1983

Long-term treatment of central precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. Effects on somatic growth and skeletal maturation.

The gonadotropin-releasing hormone-like agonist D-Trp6-Pro9-NEt-LHRH (LHRHa) has been shown to induce a reversible short-term suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. Since accelerated statural growth and bone maturation are clinical features of precocity not well controlled by conventional therapies, we examined the effects of prolonged LHRHa therapy for 18 consecutive months on growth and skeletal maturation in nine girls with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin pulsations and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (+/- S.E.M.) of 9.35 +/- 0.64 cm per year during the 19 months before treatment to 4.58 +/- 0.60 cm per year during treatment (P less than 0.001). Bone age advanced a mean of 9.4 +/- 2.3 months during treatment. These changes resulted in a mean increase of 3.3 cm in predicted height (P less than 0.01). Complete suppression of the pituitary-gonadal axis can be maintained by LHRHa therapy, resulting in slowing of excessively rapid growth and skeletal maturation and in increased predicted adult height in girls with precocious puberty.

Age Determination by Skeleton↗
PubMed1983

Corticotropin releasing factor produces increases in brain excitability and convulsive seizures in rats.

Corticotropin releasing factor (CRF) is a 41-residue peptide, capable of stimulating the secretion of corticotropin (ACTH)-like and beta-endorphin-like immunoreactivity from the adenohypophysis. Low doses of CRF (0.0015-0.15 nM) given intracerebroventricularly (i.c.v.) produced changes in electrographic activity suggestive of increased arousal. Higher doses of CRF (1.5-3.75 nM) induced, over a period of 3-7 h, electrographic and behavioral signs of seizure activity indistinguishable from those which occur following electrical 'kindling' of the amygdala.

Animals↗
PubMed1983

Sequence analysis of rat hypothalamic corticotropin-releasing factor with the o-phthalaldehyde strategy.

Sequence analysis was performed on a 41-residue polypeptide that has been identified as the predominant form of high intrinsic corticotropin-releasing activity of rat hypothalamus. The sequence of residues 1-39 of this corticotropin-releasing factor (CRF) was determined by Edman degradation of a partially purified peptide in a highly sensitive spinning cup sequencer after selective blocking of CRF or its main contaminant with o-phthalaldehyde. This approach was validated by peptide mapping of CRF of a highly purified preparation. Peptide mapping was accomplished with reverse-phase high-pressure liquid chromatography of CRF fragments obtained by digestion with clostripain. The identities of the fragments cleaved from CRF were established by chromatographic comparison with synthetic peptides, amino acid analysis, and Edman degradation. On the basis of these experiments, the primary structure of rat hypothalamic CRF was established to be H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu- Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn - Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2. It is expected that the o-phthalaldehyde strategy will facilitate the sequence analysis of partially purified peptides containing proline residues.

Amino Acid Sequence↗
PubMed1983

Corticotropin releasing factor decreases postburst hyperpolarizations and excites hippocampal neurons.

Corticotropin releasing factor in concentrations of 15 to 250 nanomoles per liter increased the spontaneous discharge frequency and decreased the size of hyperpolarizations after burst discharges in CA1 and CA3 pyramidal neurons of rat hippocampal slices. Concentrations greater than 250 nanomoles per liter also depolarized the cells. These excitatory actions of corticotropin releasing factor may involve a novel calcium-dependent process.

Action Potentials↗
PubMed1983

Effects of human pancreatic tumour growth hormone releasing factor on growth hormone and somatomedin C levels in patients with idiopathic growth hormone deficiency.

Human pancreatic tumour growth hormone releasing factor (hpGRF-40) 10 micrograms/kg was administered intravenously to 6 normal young men and 12 adult patients who had presented in childhood with growth hormone (GH) deficiency (7 patients had isolated GH deficiency, 4 had multiple anterior pituitary hormone deficiencies, and 1 had Hand-Schüller-Christian [HSC] disease). hpGRF-40 administration increased serum GH concentrations in all normal subjects and in 3 of 7 patients with isolated GH deficiency and in the 1 with HSC disease; however, the mean serum GH concentration in the patients who responded was less than that of the normal subjects. Somatomedin C concentrations were increased 24 h after a single dose of hpGRF-40 in 8 of 10 patients with GH deficiency. All subjects experienced flushing in response to hpGRF-40. A patient with isolated GH deficiency received 0.33 micrograms/kg hpGRF-40 every 3 h for 5 days. Despite the modest increase in GH in response to a subsequent dose of 10 micrograms/kg hpGRF-40, serum somatomedin C levels increased within 12 h from 0.06 to 0.1 U/ml and peaked at 0.36 U/ml at 72 h; in addition the patient with HSC disease, treated with hpGRF-40 daily for 5 days, demonstrated an increase in somatomedin C from 0.4 to 0.58 U/ml. The increase after hpGRF-40 in serum GH levels in this patient and the similar or greater responses in 3 of 7 patients suggest that at least some of these patients may have hypothalamic GH-releasing-hormone deficiency. hpGRF-40 may be useful in distinguishing pituitary disease from hypothalamic disease. After hpGRF-40 administration serum somatomedin C levels may increase without a change in serum immunoreactive GH concentrations. Further studies are needed to determine whether hpGRF-40 is useful in promoting linear growth in children with GH deficiency.

Adult↗
PubMed1983

Synthetic corticotropin-releasing factor stimulates secretion of immunoreactive beta-endorphin/beta-lipotropin and ACTH by human fetal pituitaries in vitro.

Synthetic ovine CRF, in an amount approximating that found in pituitary portal plasma of the rat, induced a significant increase in the secretion of both ACTH and immunoreactive beta-endorphin/beta-LPH (i beta-END/LPH) by human fetal hemipituitaries in an in vitro superfusion system. This finding suggests that a molecule similar to synthetic ovine CRF may be a physiologic hypothalamic releasing factor in man.

Adrenocorticotropic Hormone↗
PubMed1983

Human pancreatic growth-hormone-releasing factor selectively stimulates growth-hormone secretion in man.

A growth-hormone-releasing factor has been characterised and sequenced from a pancreatic tumour removed from a patient with acromegaly. It is a 40-residue linear peptide. Synthetic human pancreatic growth-hormone-releasing factor (hpGRF-40), 1 microgram/kg bodyweight, was administered as an intravenous bolus to six healthy men. hpGRF-40 selectively stimulated growth-hormone secretion. Serum growth-hormone concentrations were increased within 5 min, reaching a peak between 30 and 60 min (20 . 4 +/- 6 . 5 ng/ml compared with 2 . 1 +/- 0 . 1 ng/ml after placebo). Serum levels of prolactin, thyrotropin, luteinising hormone, and corticotropin (measured indirectly through plasma cortisol) were not increased after administration of hpGRF-40. Similarly, the concentrations of blood glucose, plasma insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, and somatostatin were unaffected by hpGRF-40. There were no changes in blood pressure, pulse rate, or body temperature, and no side-effects were noted. The characteristics of this peptide fulfil many of the criteria required of the hypophysiotropic growth-hormone-releasing hormone. hpGRF holds promise for a new approach to the diagnosis and treatment of various disorders of growth-hormone secretion.

Acromegaly↗
PubMed1983

Effect of angiotensin II on ACTH release in vivo: role of corticotropin-releasing factor.

The ability of angiotensin II (ANG II) to release ACTH was studied in vivo. ANG II elicited dose-related increases in plasma ACTH levels in freely-moving non-anesthetized rats. The observation that this effect was totally abolished by immunoneutralization of endogenous CRF, as well as the lack of stimulatory activity of ANG II in pharmacologically blocked animals, suggest that the induction of CRF secretion by ANG II represents an essential modulator of the ACTH-releasing potency of this peptide.

Adrenocorticotropic Hormone↗
PubMed1983

In vitro and in vivo ACTH-releasing activity of ovine CRF, sauvagine and urotensin I.

The ability of three homologous peptides, ovine corticotropin-releasing factor (CRF), sauvagine and urotensin I, to release ACTH was examined in vitro and in vivo. All three peptides exhibit statistically equivalent potencies to stimulate ACTH secretion both by cultured pituitary cells and in pharmacology blocked rats. These results suggest that all three peptides evolved from a common mammalian precursor that possessed high hypophysiotropic potency.

Adrenocorticotropic Hormone↗
PubMed1983

Flow cytometric separation of gonadotrophs from dispersed rat pituitaries using a fluorescent GnRH antagonist.

A gonadotropin-releasing hormone (GnRH) antagonist, [Ac-delta 3 Pro1,pFDPhe2,DTrp3,DLys6[-GnRH, was synthesized, conjugated to tetramethyl rhodamine, and found to retain GnRH antagonist activity. The fluorescent compound was used to label dispersed pituitary cells from 14-17 day-old Sprague-Dawley female rats. A subset comprising approximately 10% of the pituitary population was specifically labeled with a mean intensity of fluorescence 4.9-fold higher than the unlabeled population. The labeled cells were larger on average than the general population as inferred by forward narrow angle light scatter intensity measurements, and more granular as inferred by right angle light scatter intensity. Cells were sorted on the basis of fluorescent intensity: gonadotrophs were found to be concentrated in the rhodamine-positive fraction 5- or 6-fold relative to unfractionated cells, and 21- or 28-fold relative to rhodamine-negative fraction cells based on LH or FSH content, respectively. Gonadotrophs comprised 73 +/- 3.9% of the rhodamine-positive fraction by immunocytochemical staining. Sorted rhodamine-positive cells were cultured and found to be fully functional with respect to subsequent challenge with 30 nM GnRH. We conclude that the use of the fluorescent GnRH antagonist in conjunction with a multi-parameter cell sorter allows the purification of gonadotrophs, indicating, as expected, that these cells have a significantly higher level of GnRH binding sites than the general pituitary population. This technology should prove generally valuable in endocrine research.

Animals↗
PubMed1983

Methodological considerations in culturing peptidergic neurons.

Both explant and dispersed cell culture preparations of brain tissue provide a means to directly assess the functions of neuropeptide-containing brain cells isolated from the complex influences present in vivo. The validity of the approach depends on reproducibility of observations. In dispersed cell cultures, we find that cell responses, as determined by secretion of the peptide somatostatin, have remained relatively constant both quantitatively and qualitatively over numerous preparations. In addition, for pharmacologic studies on somatostatin secretion, data from several laboratories are in good agreement. The validity of the dispersed cell approach also depends on whether the pharmacologic and physiologic behavior of cells parallels that expected of excitable tissue. The variability of the explant cultures from culture dish to culture dish makes quantitative experiments, such as demonstrated with the dispersed cultures, difficult. On the other hand, explant cultures better maintain the integrity of the tissue components, so that interactions between neurons and glial cells could occur as in vivo. The long-term health and viability of neuropeptidergic cells in explant and dispersed culture make both preparations potentially useful models to examine central nervous system physiology. Future work with such preparations must eventually address the problems of culturing adult brain tissue, the precise nutrient and hormonal requirements of brain cells, so that undefined medium components, such as serum, can be eliminated from the culture environment, and the general question of whether observations made in vitro facilitate our understanding of intact brain physiology.

Animals↗