Τίτλος:
Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective: Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. Methods: The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 μg of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1α stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), folowing suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. Results: Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1α administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated with a significant reduction in adrenocortical reserve. A significant increase in adrenal weights and a decrease in thymus weights were observed in both short- and long-term hyperthyroidism. Conclusions: The available data confirms that hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally affected still remains unclear. Despite the sustained hyperactivity of the HPA axis, long-term experimentally-induced hyperthyroidism is associated with diminished adrenal functional reserve. The alterations in HPA function in states of disturbed thyroid function were found to be somewhat more pronounced as the duration of thyroid dysfunction increased. © 2005 Society of the European Journal of Endocrinology.
Συγγραφείς:
Johnson, E.O.
Kamilaris, T.C.
Calogero, A.E.
Gold, P.W.
Chrousos, G.P.
Περιοδικό:
European Journal of Endocrinology
Λέξεις-κλειδιά:
corticosterone; corticotropin; corticotropin releasing factor; dexamethasone; insulin; interleukin 1alpha; placebo; steroid binding protein; thyroid hormone; thyroxine, adrenal cortex; adrenal gland; animal experiment; animal tissue; article; controlled study; corticosterone blood level; corticotropin blood level; endocrine function; hormone response; hyperadrenocorticism; hyperthyroidism; hypoglycemia; hypothalamus hypophysis adrenal system; in vivo study; male; nerve stimulation; nonhuman; organ weight; priority journal; protein cerebrospinal fluid level; rat; rat strain; thymus; thyroid hormone blood level; thyroidectomy; time, Adrenal Glands; Adrenocorticotropic Hormone; Animals; Corticosterone; Hyperthyroidism; Hypoglycemia; Hypoglycemic Agents; Hypothalamo-Hypophyseal System; Insulin; Interleukin-1; Male; Organ Size; Pituitary-Adrenal System; Rats; Rats, Sprague-Dawley; Thymus Gland; Thyroxine; Transcortin
