Effects of Dexamethasone on Central and Peripheral ACTH Systems in the Rat

Carnes, Molly; Barksdale, Charles M.; Kalin, Ned H.; Brownfield, Mark S.; Lent, Stephanie J.

doi:10.1159/000124718

Cited by 41 publications

(15 citation statements)

References 23 publications

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“…Several studies have examined the distribution of dex amethasone binding sites in brain, and have suggested that dexamethasone may act centrally to inhibit ACTH and cor ticosterone secretion [8,II]. In contrast, studies by De Kloet et al [5] and Carnes et al [4] indicate that dexametha sone can affect ACTH secretion by a more direct mecha nism at the level of the pituitary. What is clear from these and other studies is that even if dexamethasone acts directly on the pituitary, higher brain centers can influence the HPA axis, especially during stress [18].…”

Section: Discussionmentioning

confidence: 99%

Effects of Systemic and Intracerebroventricular Cysteamine on Dexamethasone-Induced Suppression of Corticosterone Levels in the Rat

Radke

Vincent²

1988

Neuroendocrinology

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To investigate whether somatostatin systems plays a significant role in the regulation of the hypothalamic-pituitary-adrenal axis, the effects of cysteamine, a drug which reduces somatostatin levels, on the dexamethasone-induced suppression of plasma corticosterone levels were examined in the rat. Male Long Evans rats were handled daily for 1 week prior to receiving a standard dexamethasone suppression test. On the 1st day, rats received a 9.00 a.m. saline injection and blood samples were taken from the tail at 1.00 p.m. On the 2nd day, rats received dexamethasone or saline at 9.00 a.m. and a second blood sample was taken at 1.00 p.m. Experimental groups were pretreated with systemic injections of cysteamine, 5 min or 14 h, prior to receiving dexamethasone. Additional groups, previously implanted with guide cannulae, were given an infusion of cysteamine or saline into the lateral ventricle 14 h prior to dexamethasone. Circulating corticosterone levels were determined by radioimmunoassay. Rats were sacrificed immediately following each experiment and the hypothalamus dissected and assayed for levels of somatostatin immunoreactivity. The results of the first experiment showed that dexamethasone (10 µg/kg) alone reduced plasma corticosterone levels from control values (174 + 36 ng/ml) to undetectable levels ( < 25 ng/ml). Pretreatment with cysteamine 5 min prior to dexamethasone, while having no significant effect on basal corticosterone levels, completely blocked the dexamethasone-induced suppression of corticosterone levels. Similar observations were obtained with rats pretreated with cysteamine 14 h prior to dexamethasone. In contrast, intracerebroventricular cysteamine pretreatment did not block the dexamethasone-induced suppression of corticosterone levels. These results add further evidence in support of an involvement of somatostatin systems in the regulation of the hypothalamic-pituitary-adrenal axis.

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Section: Discussionmentioning

confidence: 99%

Effects of Systemic and Intracerebroventricular Cysteamine on Dexamethasone-Induced Suppression of Corticosterone Levels in the Rat

Radke

Vincent²

1988

Neuroendocrinology

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“…Dexamethasone is a synthetic glucocorticoid which inhibits the secretion of ACTH and cortisol. acting at the level of the hypothalamus to block the release of CRH, and at the level of the pituitary gland to block the ACTH response to CRH (22). The study was carried out using two groups of eight rams during the regressing phase of the reproductive cycle (6 weeks after a change from short to long days).…”

Section: Lh Responses To Nmda 315mentioning

confidence: 99%

Luteinizing Hormone Responses to N‐Methyl‐D,L‐Aspartate During a Photoperiodically‐lnduced Reproductive Cycle in the Ram

Lincoln

1991

J Neuroendocrinology

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Aspartate and glutamate represent a major class of excitatory amino-acid neurotransmitters in the vertebrate brain, and stimulation of glutaminergic receptors by the specific agonist N-methyl-D,L-aspartate (NMDA) induces luteinizing hormone-releasing hormone (LHRH) and LH secretion. In this study, we used NMDA as a probe to investigate the hypothalamic regulation of LH secretion at different stages of a reproductive cycle in Soay rams induced by exposure to alternating 16-week periods of long and short days. NMDA (20 mg/kg) injected intravenously caused an acute increase in blood plasma concentrations of LH, with a significant increase within 2 to 4 min, and peak levels within 20 min. The magnitude of the response changed markedly during the cycle; it was greatest in the sexually inactive phase under long days (with a linear dose-response over the range 1 to 20 mgikg NMDA) and least in the sexually active phase under short days (only 20 mg/kg NMDA produced a small response). Pituitary responsiveness to a standard dose of LHRH (5.3 ng/kg iv) varied only slightly at the different stages and could not account for the observed changes in the LH response to NMDA. There were the expected changes in the endogenous pattern of LH secretion during the cycle, with high frequency LH pulses occurring during the sexually active phase. There was an inverse relationship between the frequency of LH pulses and the LH response to NMDA. Pretreatment of rams with an LHRH antagonist (36 pg/kg iv; Syntex, RS18286) totally blocked the LH response to both NMDA and LHRH, while in a separate study, treatment with dexamethasone (synthetic glucocorticoid, 133.4 pglkg iv) partially blocked the LH responses. The overall results indicate that NMDA stimulates LHRH secretion in the ram and the response is independent of the activation of the hypothalamo-pituitary-adrenal axis. The variation in the LH response during the reproductive cycle may reflect changes in the releasable stores of LHRH in the median eminence. These appear to be depleted in the sexually active phase, when LHRH is secreted in pulses at high frequency. The variation in the response to NMDA may also reflect changes in release of endogenous excitatory amino-acids, which act via NMDA receptors to form part of the physiological regulation of the reproductive cycle in the ram.The dicarboxylic amino-acids aspartate and glutamate represent a major class of excitatory neurotransmitters in the vertebrate brain ( I ) . These amino-acids have excitatory effects through at least three classes of receptors of which the N-methyl-D,Laspartate (NMDA) receptor class is best characterized, and these receptors are apparently involved in the neural control of reproduction (2). Studies in the rat have shown that the administration of NMDA causes the release of luteinizing hormone (LH) from the anterior pituitary gland by inducing the secretion of LHreleasing hormone (LHRH) from the hypothalamus (3, 4), and there is evidence that both NMDA and non-NMDA excitatory amino-acid receptors are in...

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“…When a signal occurs approximately every 100 min, as in these larger ultradian secretory episodes, the Nyquist frequency demands that the sampling interval be at least half the signal frequency, i.e., 50 min, in order to detect the signal [ 15]. Most previous investi gations of rhythmic secretion of ACTH in the rat have sacrificed groups of animals at different times of day, usually at 4-hour intervals or greater [ 1,2,8,11,13], This sampling interval is too long to detect ultradian rhythms. In addition, when groups of different animals are used at each time point, the individual va riation among animals in plasma ACTH levels tends to flatten out the data and obscure any rhythm.…”

Section: Larger Ultradian Rhythmmentioning

confidence: 99%

Plasma Adrenocorticotropic Hormone in the Rat Demonstrates Three Different Rhythms within 24 h

Carnes

Lent²,

Feyzi

et al. 1989

Neuroendocrinology

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Secretion of adrenocorticotropic hormone (ACTH) by the anterior pituitary is rhythmic and episodic, as reflected by fluctuations in plasma concentrations of ACTH. The present work was designed to further characterize the patterns of ACTH secretion that occur simultaneously within a 24-hour period in the rat. To accomplish this, blood collection protocols with sampling intervals of 2 min, 15 min, and 4 h were used in awake, chronically cannulated rats. Plasma samples were assayed for immunoreactive ACTH, and resultant data were analyzed for significant pulsatile secretory episodes. We observed three different patterns of ACTH secretion within a 24-hour period. Circadian variation occurred with peak plasma ACTH levels in the early evening. In addition, plasma ACTH exhibited two types of episodic ultradian variation: (1) episodic bursts with variable amplitudes that occurred approximately three times per hour which have been referred to as ‘micropulses’, and (2) more prolonged elevations of plasma ACTH that occurred approximately 14 times in 24 h which have been referred to as ‘larger ultradian’ secretory episodes. These latter episodes appeared to consist of groups of relatively high amplitude micropulses. The physiological significance, functional interactions, and location of the controlling oscillator(s) of these different rhythms remain to be determined.

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Effects of Dexamethasone on Central and Peripheral ACTH Systems in the Rat

Cited by 41 publications

References 23 publications

Effects of Systemic and Intracerebroventricular Cysteamine on Dexamethasone-Induced Suppression of Corticosterone Levels in the Rat

Effects of Systemic and Intracerebroventricular Cysteamine on Dexamethasone-Induced Suppression of Corticosterone Levels in the Rat

Luteinizing Hormone Responses to N‐Methyl‐D,L‐Aspartate During a Photoperiodically‐lnduced Reproductive Cycle in the Ram

Plasma Adrenocorticotropic Hormone in the Rat Demonstrates Three Different Rhythms within 24 h

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