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H S Chowdrey

Publications and source records attributed to H S Chowdrey.

At least 37 records · Page 2Linked to original sources
PubMed1994

The diurnal expression of genes encoding vasopressin and vasoactive intestinal peptide within the rat suprachiasmatic nucleus is influenced by circulating glucocorticoids.

The mammalian suprachiasmatic nucleus (SCN) is the endogenous pacemaker generating the diurnal rhythm of the stress hormones ACTH and glucocorticoid secretion. In the present study, we have employed male rats entrained to a 12:12 h (light:dark) photoperiod to investigate the effects of chronic and acute administration of exogenous glucocorticoids upon the diurnal expression of vasopressin and vasoactive intestinal peptide (VIP) mRNA in the SCN by semiquantitative in situ hybridization histochemistry. Chronic administration of exogenous glucocorticoids significantly enhanced vasopressin mRNA expression only at zeitgeber time (ZT) 5, while the otherwise rhythmic expression of vasopressin mRNA was unaffected at ZT11, ZT17 and ZT23. In contrast, the same treatment abolished the rhythmic expression of VIP mRNA resulting in constantly elevated mRNA levels. In adrenalectomized rats given an overnight supplement of dexamethasone in their drinking water, the expression of both vasopressin and VIP mRNA in the SCN was elevated the following morning at ZT6 when compared to adrenalectomised rats kept on 0.9% saline. These results suggest that glucocorticoids influence the expression of vasopressin during a narrow window of time in the diurnal cycle coinciding with the time where entrainment of the circadian pacemaker with non-photic cues is possible. Constantly elevated levels of glucocorticoids may also interfere with the suprachiasmatic expression of VIP mRNA which is thought to be driven by photic cues.

Animals↗
PubMed1994

Role of central catecholamines in the modulation of corticotrophin-releasing factor mRNA during adjuvant-induced arthritis in the rat.

The development of adjuvant-induced arthritis in the rat is associated with an activation of the hypothalamo-pituitary-adrenal axis. In the Piebald-Viral-Glaxo strain of rat there is however a paradoxical decrease in corticotrophin-releasing factor (CRF) mRNA in the hypothalamic paraventricular nucleus (PVN) and a decrease in CRF-41 peptide release into the hypophysial portal blood with increasing severity of disease. In the present study we have investigated the role of endogenous catecholamines within the PVN as possible inhibitory factors acting on CRF neurons during adjuvant-induced arthritis. Noradrenaline (NA) concentrations were approximately doubled in the PVN of arthritic animals. Depletion of endogenous catecholamines following direct 6-OHDA lesions of the PVN resulted in a significant depletion in PVN NA. The increase in NA observed in arthritic animals appears to have a protective role since depletion of NA increased the severity of the disease. Neither the increase in circulating levels of corticosterone nor the decrease in CRF mRNA in the PVN were prevented following NA depletion. Our results suggest that modification of central neurotransmitter systems are able to influence the severity of adjuvant-induced arthritis.

Animals↗
PubMed1994

Chronic administration of glucocorticoids directly upregulates prepro-neuropeptide Y and Y1-receptor mRNA levels in the arcuate nucleus of the rat.

The complete sequence of the cDNA encoding the neuropeptide Y (NPY) Y1-receptor has recently been deduced from a rat brain library, and the presence of messenger ribonucleic acid (mRNA) encoding Y1-receptor protein has been demonstrated within the brain. Using quantitative in situ hybridization histochemistry, the content and distribution of Y1-receptor and preproNPY mRNAs have been investigated in the hypothalamic arcuate nucleus of adrenalectomized rats receiving glucocorticoid replacement therapy for 12 days by means of either high doses of dexamethasone in their drinking water or by subcutaneous corticosterone pellets. Basal metabolic parameters such as weight gain or loss, blood glucose and plasma insulin were monitored: Dexamethasone treatment induced weight loss and a state of hyperinsulinemia with normoglycemia, while corticosterone treated animals displayed metabolic parameters identical to sham ADX animals. Within the arcuate nucleus of glucocorticoid treated animals, levels of Y1-receptor and preproNPY mRNAs were increased. In contrast, adrenalectomy itself had no effect upon Y1-receptor mRNA levels or preproNPY mRNA levels in the arcuate nucleus. These studies demonstrate that glucocorticoids exert a stimulatory action on levels of Y1-receptor mRNA and preproNPY mRNA levels in the hypothalamic arcuate nucleus. This is the first evidence to suggest that the expression of a neuropeptide-receptor gene in the central nervous system may be directly sensitive to peripheral hormonal signals.

Adrenalectomy↗
PubMed1994

Neuropeptide-Y potentiates the secretion of vasopressin from the neurointermediate lobe of the rat pituitary gland.

Neuropeptide-Y (NPY) is colocalized with vasopressin and oxytocin in magnocellular neurons of the hypothalamo-neurohypophysial system, and a very high density of NPY-binding sites is present within the neurohypophysis. To investigate the possibility that NPY exerts a modulatory role on the release of neurohypophysial hormones, we have studied the actions of NPY on potassium-evoked release of vasopressin and oxytocin from the rat neurointermediate lobe in vitro. NPY dose-dependently potentiated vasopressin release evoked by high extracellular potassium (56 mM), with a maximal enhancement of 223% (10(-7) M NPY). A similar effect was obtained with the Y2-selective agonist NPY-(13-36). In contrast, no effect on the potassium-evoked release of oxytocin was observed at this concentration. In the absence of Ca2+ in the incubation medium, NPY did not potentiate vasopressin secretion, indicating that the effect of NPY on potassium-evoked secretion of neurohypophysial vasopressin is critically dependent on extracellular calcium ions. The number of neurohypophysial NPY-binding sites is drastically down-regulated in animals subjected to chronic osmotic stimulation. In the present study, it was observed that the potentiating effect of NPY on vasopressin secretion was completely abolished in neurointermediate lobes recovered from animals that had been drinking 2% NaCl for 12 days, reflecting the concomitant down-regulation of neurohypophysial NPY-binding sites observed during this state. Finally, it was confirmed that stimulation by high K+ significantly evoked the release of endogenous NPY from neurointermediate lobes of the pituitary gland. The present results provide evidence that NPY selectively and potently enhances evoked vasopressin secretion. Considering the coexistence of the two neuropeptides in magnocellular hypothalamo-neurohypophysial neurons, this action is likely to be part of an autostimulatory feedforward loop. NPY may be an important component in the mechanisms associated with the control of body fluid homeostasis.

Animals↗
PubMed1994

Pharmacokinetics and efficacy of the long-acting somatostatin analogue somatuline in acromegaly.

The aim of this work was to assess the use of a sustained-release formulation of somatuline, a long-acting analogue of somatostatin, in the treatment of acromegaly. Fifteen patients with active acromegaly, as defined by random growth hormone (GH) levels greater than 10 mU/l, which fail to be suppressed to less than 5 mU/l following an oral glucose load, were studied. Somatuline was administered as an intramuscular injection in two regimens: eight patients were given a single injection of the sustained-release formulation and blood samples taken over the next month for the measurement of both basal levels of GH and the GH response to thyrotrophin-releasing hormone; and eight patients were given injections of the sustained-release formulation at 2-week intervals over a 6-month period and basal plasma GH levels and the GH response to both an oral glucose load and to thyrotrophin-releasing hormone was assessed. Following a single intramuscular dose of the sustained-release preparation, random GH levels were reduced to below 10 mU/l in five patients and by greater than 50% of basal levels in the remainder. The insulin-like growth factor I (IGF-I) levels fell to within the normal range in three patients. In the long-term efficacy study. GH levels were reduced to < 10 mU/l in 7/8 patients. The IGF-I levels were normalized in four patients. Five of the eight patients experienced diarrhoea, two of mild and three of moderate severity; none of the patients withdrew from the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1994

Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis.

We have investigated the effects of monosodium glutamate (MSG) lesioning of the arcuate nucleus on both central and peripheral components of the hypothalamo-pituitary-adrenocortical (HPA) axis under basal conditions and under acute and chronic stress. Plasma ACTH levels were lower in MSG-lesioned rats (27 +/- 7 pg/ml) compared with controls (71 +/- 18 pg/ml) while corticosterone levels were elevated (523 +/- 84 ng/ml compared with 176 +/- 34 ng/ml). Quantitative in situ hybridization histochemistry revealed that corticotrophin-releasing factor mRNA levels in the medial parvocellular part of the hypothalamic paraventricular nucleus were significantly lower in MSG-treated rats. MSG lesioning resulted in an enhanced response of corticosterone to restraint stress (1309 +/- 92 ng/ml compared with 628 +/- 125 ng/ml in sham-lesioned animals), while ACTH responses to restraint stress in MSG-lesioned and sham-MSG groups were not significantly different (160 +/- 24 pg/ml and 167 +/- 24 pg/ml respectively). These data suggest that MSG-lesioned rats have an increased adrenocortical sensitivity. In rats subjected to the chronic osmotic stimulus of drinking 2% saline for 12 days, plasma ACTH levels were significantly reduced (15 +/- 5 pg/ml) and the ACTH and corticosterone responses to restraint stress were eliminated. ACTH levels were also reduced in MSG-treated animals given 2% saline and the ACTH response to acute stress remained absent in these animals. However, a robust corticosterone response to restraint stress was observed in saline-treated MSG-lesioned rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Interleukin-1 beta measured by radioimmunoassay in the rat spleen and thymus is increased during chronic inflammatory stress.

We have developed an extraction method and radioimmunoassay for the measurement of interleukin-1 beta (IL-1 beta) in rat tissues, using an antibody specific for IL-1 beta, IL-1 beta was detected in the spleen and thymus of control rats. Adrenalectomy (ADX) had no effect upon control levels of IL-1 beta. In animals with adjuvant-induced arthritis, IL-1 beta content in the spleen and thymus increased after 14 days. These increases in tissue IL-1 beta contents were not evident in ADX arthritic animals. We conclude that IL-1 beta synthesis is stimulated in tissues of the immune system following the development of adjuvant-induced arthritis. Failure to observe elevated levels of tissue IL-1 beta in ADX arthritic rats may be evidence for tissue depletion due to increased IL-1 beta release in the absence of circulating corticosteroids.

Adrenalectomy↗
PubMed1993

Preprotachykinin A gene expression in distinct hypothalamic and brain stem regions of the rat is affected by a chronic osmotic stimulus: a combined immunohistochemical and in situ hybridization histochemistry study.

Chronic osmotic stimulation influences the hypothalamoadenohypophysial axis by inhibiting the synthesis of corticotrophin releasing factor (CRF-41) in the parvocellular subdivision of the paraventricular nucleus (PVN) and, subsequently, the secretion of adrenocorticotrophin (ACTH) from the adenohypophysis. Using quantitative in situ hybridization histochemistry, we have investigated the effect of chronic osmotic stimulation on preprotachykinin A (PPT-A) mRNA levels in a number of brain areas known to send substance P-containing projections to the medial parvocellular part of the PVN. Chronic osmotic stimulation increased PPT-A gene expression in the lateral hypothalamic area, the arcuate nucleus, the catecholaminergic brain stem areas A2, C1, and C2, although PPT-A mRNA levels in the bed nucleus of the stria terminalis, the medial preoptic nucleus, the caudate-putamen, and the A1 were unaffected by chronic osmotic stimulation. In addition, immunohistochemical staining of substance P-immunoreactive elements contained within the same areas was carried out on colchicine-treated animals. Generally, those areas responding to the osmotic stimulus with increased PPT-A mRNA synthesis showed increased numbers of substance P-immunoreactive perikarya, suggesting that increased levels of mRNA are associated with increased peptide synthesis. These results provide evidence that central endogenous substance P contained in brain regions projecting to the paraventricular nucleus could have an inhibitory influence over the synthesis of CRF-41 during a chronic osmotic stimulus.

Animals↗
PubMed1993

Effects of glucocorticoids and chronic inflammatory stress upon anterior pituitary interleukin-6 mRNA expression in the rat.

During development of adjuvant arthritis (AA) in the rat, anterior pituitary interleukin-6 (IL-6) mRNA expression was increased. Following adrenalectomy and AA there was a further increase in the accumulation of pituitary IL-6 transcript. Corticosterone (B) replacement in adrenalectomized (ADX) animals resulted in a dose-dependent reduction in pituitary IL-6 mRNA accumulation, while in ADX plus AA animals these effects of B were less marked. Cyclosporine A (CsA) markedly reduced the AA-induced increase in IL-6 mRNA. These data are consistent with an immunologically-mediated activation of pituitary IL-6 mRNA in AA, which may contribute to the increased activity of the pituitary-adrenal axis seen in this condition.

Adrenalectomy↗
PubMed1993

Substance P inhibits the release of anterior pituitary adrenocorticotrophin via a central mechanism involving corticotrophin-releasing factor-containing neurons in the hypothalamic paraventricular nucleus.

Chronic osmotic stimulation influences the hypothalamo-adenohypophysial axis by inhibiting the synthesis of hypothalamic corticotrophin-releasing factor (CRF-41) and subsequently the secretion of basal and adrenalectomy-elevated adrenocorticotrophin from the adenohypophysis. In the present study, we used a substance P antagonist to test the hypothesis that this inhibition is mediated centrally by substance P or other tachykinins. In control rats and rats given 2% saline to drink for 12 days, intracerebroventricular administration of a substance P antagonist elevated plasma adrenocorticotrophin and corticosterone levels. Using quantitative in situ hybridization histochemistry, it was also demonstrated that CRF mRNA increased in the medial parvocellular division of the paraventricular nucleus of saline-treated as well as control rats 6 h after intracerebroventricular administration of the antagonist, while vasopressin mRNA in the medial parvocellular division of the paraventricular nucleus was increased in the control animals only. These results provide evidence that central endogenous substance P has an inhibitory influence over the synthesis and release of CRF-41 both under normal conditions and during a chronic osmotic stimulus.

Adrenocorticotropic Hormone↗
PubMed1993

Direct stimulation of the pituitary by transfer of activated leucocytes.

Some strains of rat develop arthritis, and have profoundly elevated adrenocorticotropin (ACTH) and corticosterone, following intradermal injection of an adjuvant containing heat-killed mycobacteria. Transfer to syngeneic recipients of immune spleen (IS) cells taken from arthritic rats 14 days after injection of the adjuvant, but not of non-immune cells, causes increased circulating ACTH and increased pituitary proopiomelanocortin (POMC) mRNA. Transfer of immune cells does not transfer the disease, but does protect recipients from subsequent challenge with the adjuvant. In these immune-protected rats, the secondary immune response raises ACTH and POMC to levels similar to those seen in arthritic rats. These data show that endogenous inflammatory mediators have direct actions on the neuroendocrine system.

Adrenocorticotropic Hormone↗
PubMed1993

Effects of adrenalectomy and hypertonic saline on neuropeptide Y content in the posterior pituitary of the rat.

We have examined the effects of adrenalectomy (ADX) on neuropeptide Y (NPY) content in the posterior pituitary of the rat. In rats given 2% saline to drink for 12 days, plasma osmolality increased to 343 +/- 18 compared to 291 +/- 5 mosm/kg in control animals on water (mean +/- SEM). Hypertonic saline treatment resulted in increased posterior pituitary NPY content measured by radioimmunoassay (2.42 +/- 0.36 ng) compared to the control group (1.18 +/- 0.16 ng). Total NPY immunoreactivity in tissue extracts coeluted with synthetic NPY(1-36) on reversed-phase high-performance liquid chromatography. In ADX rats given 2% saline to drink, plasma osmolality increased to 355 +/- 35 mosm/kg, but posterior pituitary NPY content was not different from the control group (1.41 +/- 0.11 ng). Immunohistochemical staining for NPY in the posterior pituitary also revealed a saline-induced increase in the number of NPY-immunoreactive nerve fibers, an increase which was not evident in the ADX group. No NPY immunoreactivity was observed in the intermediate zone. These results are the first evidence that the saline-induced increase in NPY in the posterior pituitary is under corticosteroid control.

Adrenalectomy↗
PubMed1993

Neuropeptide Y mRNA and immunoreactivity in hypothalamic neuroendocrine neurons: effects of adrenalectomy and chronic osmotic stimulation.

Neuropeptide Y (NPY) coexists with vasopressin or oxytocin in magnocellular neurons of the hypothalamo-neurohypophysial tract. Using quantitative in situ hybridization histochemistry and immunohistochemistry, we have studied the effects of adrenalectomy and chronic osmotic stimulation, either alone or in combination, on NPY mRNA expression and NPY immunoreactivity in magnocellular neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, and arcuate nucleus (Arc). Adrenalectomy and chronic osmotic stimulation each increased NPY mRNA levels in magnocellular neurons of the PVN and SON, while the combination of both treatments had an additive effect. In the Arc, only the combination of adrenalectomy and chronic osmotic stimulation increased NPY mRNA levels. Chronic osmotic stimulation also resulted in a marked increase of NPY-immunoreactive magnocellular perikarya in the PVN and SON. In contrast, adrenalectomy had only minor effects on the number of NPY-immunoreactive magnocellular PVN/SON perikarya. Neither chronic osmotic stimulation nor adrenalectomy affected the number of NPY-immunoreactive Arc perikarya. However, adrenalectomy decreased the number of NPY-immunoreactive nerve terminals in the external zone of the median eminence, while chronic osmotic stimulation increased the number of immunoreactive nerve fibers in the internal zone of the median eminence. The present study provides evidence that adrenalectomy and chronic osmotic stimulation can separately influence NPY gene transcription in magnocellular hypothalamo-neurohypophysial neurons, while only the combined effect of adrenalectomy and chronic osmotic stimulation increases NPY mRNA expression in neurons of the Arc.

Adrenalectomy↗