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Hypothalamic and suprahypothalamic effects of prolonged treatment with dexamethasone in the rat.
J Endocrinol Invest. 1991 Apr; 14(4):277-86.JE

Abstract

Corticosteroid type I and II receptors mediate the negative feedback effects of these hormones at various central nervous system sites involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. To examine the effects of chronic treatment with dexamethasone (DEX), a type 2 receptor agonist, on the regulation of this axis, male Sprague-Dawley rats weighing 200-250 g were given daily injections of DEX for 1,2,3, and 4 weeks or were treated with a subcutaneously implanted DEX-releasing minipump for one week. At the end of treatment, the animals were weighed and brains and truncal blood were collected. Daily intermittent DEX treatment reduced the body weight of the rats in a time-dependent fashion, but had little or no effect on their wet brain weight. Plasma ACTH and corticosterone, measured by RIA, were fully suppressed after one week of intermittent treatment and did not show any further reduction in rats treated for longer periods. In these animals, the content of immunoreactive corticotropin-releasing hormone (iCRH), arginine vasopressin (AVP), ACTH and beta-endorphin (beta-EP) in the hypothalamus, hippocampus, cerebral cortex and cerebellum and pituitary ACTH content did not show any difference compared to vehicle-treated rats. In contrast, continuous DEX treatment increased iCRH content in the cortex, reduced AVP content in the cerebellum, increased ACTH content in the hippocampus, decreased ACTH and beta-EP content in the hypothalamus, and reduced pituitary ACTH content. Hypothalami explanted from rats treated with DEX for one week released lower basal amounts of iCRH in vitro and did not respond to a maximally stimulatory concentration of serotonin (5-HT), a known CRH secretagogue. Continuous DEX administration suppressed also potassium chloride-induced iCRH release. Interestingly, hypothalami explanted from rats receiving daily injection of vehicle, but not from unhandled, untreated controls, did not respond to 5-HT with an increase of iCRH release in vitro. In conclusion, prolonged and continuous, but not intermittent, administration of DEX had a strong effect on brain neuropeptide content. Both regimens of DEX reduced the hypothalamic iCRH responsiveness to stimuli in vitro. Chronic handling also decreased the responsiveness of the hypothalamus to a stimulatory neurotransmitter and may confound the interpretation of data pertinent to inhibitory mechanisms.

Authors+Show Affiliations

Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1650804

Citation

Calogero, A E., et al. "Hypothalamic and Suprahypothalamic Effects of Prolonged Treatment With Dexamethasone in the Rat." Journal of Endocrinological Investigation, vol. 14, no. 4, 1991, pp. 277-86.
Calogero AE, Liapi C, Chrousos GP. Hypothalamic and suprahypothalamic effects of prolonged treatment with dexamethasone in the rat. J Endocrinol Invest. 1991;14(4):277-86.
Calogero, A. E., Liapi, C., & Chrousos, G. P. (1991). Hypothalamic and suprahypothalamic effects of prolonged treatment with dexamethasone in the rat. Journal of Endocrinological Investigation, 14(4), 277-86.
Calogero AE, Liapi C, Chrousos GP. Hypothalamic and Suprahypothalamic Effects of Prolonged Treatment With Dexamethasone in the Rat. J Endocrinol Invest. 1991;14(4):277-86. PubMed PMID: 1650804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypothalamic and suprahypothalamic effects of prolonged treatment with dexamethasone in the rat. AU - Calogero,A E, AU - Liapi,C, AU - Chrousos,G P, PY - 1991/4/1/pubmed PY - 1991/4/1/medline PY - 1991/4/1/entrez SP - 277 EP - 86 JF - Journal of endocrinological investigation JO - J Endocrinol Invest VL - 14 IS - 4 N2 - Corticosteroid type I and II receptors mediate the negative feedback effects of these hormones at various central nervous system sites involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. To examine the effects of chronic treatment with dexamethasone (DEX), a type 2 receptor agonist, on the regulation of this axis, male Sprague-Dawley rats weighing 200-250 g were given daily injections of DEX for 1,2,3, and 4 weeks or were treated with a subcutaneously implanted DEX-releasing minipump for one week. At the end of treatment, the animals were weighed and brains and truncal blood were collected. Daily intermittent DEX treatment reduced the body weight of the rats in a time-dependent fashion, but had little or no effect on their wet brain weight. Plasma ACTH and corticosterone, measured by RIA, were fully suppressed after one week of intermittent treatment and did not show any further reduction in rats treated for longer periods. In these animals, the content of immunoreactive corticotropin-releasing hormone (iCRH), arginine vasopressin (AVP), ACTH and beta-endorphin (beta-EP) in the hypothalamus, hippocampus, cerebral cortex and cerebellum and pituitary ACTH content did not show any difference compared to vehicle-treated rats. In contrast, continuous DEX treatment increased iCRH content in the cortex, reduced AVP content in the cerebellum, increased ACTH content in the hippocampus, decreased ACTH and beta-EP content in the hypothalamus, and reduced pituitary ACTH content. Hypothalami explanted from rats treated with DEX for one week released lower basal amounts of iCRH in vitro and did not respond to a maximally stimulatory concentration of serotonin (5-HT), a known CRH secretagogue. Continuous DEX administration suppressed also potassium chloride-induced iCRH release. Interestingly, hypothalami explanted from rats receiving daily injection of vehicle, but not from unhandled, untreated controls, did not respond to 5-HT with an increase of iCRH release in vitro. In conclusion, prolonged and continuous, but not intermittent, administration of DEX had a strong effect on brain neuropeptide content. Both regimens of DEX reduced the hypothalamic iCRH responsiveness to stimuli in vitro. Chronic handling also decreased the responsiveness of the hypothalamus to a stimulatory neurotransmitter and may confound the interpretation of data pertinent to inhibitory mechanisms. SN - 0391-4097 UR - https://www.unboundmedicine.com/medline/citation/1650804/Hypothalamic_and_suprahypothalamic_effects_of_prolonged_treatment_with_dexamethasone_in_the_rat_ L2 - https://link.springer.com/article/10.1007/BF03346812 DB - PRIME DP - Unbound Medicine ER -