M.T. Jones

Diurnal variations in responsiveness of the hypothalamo-pituitary-adrenocortical axis of the rat.

Hypothalami, anterior pituitary gland segments and adrenal glands were removed from female Wistar-derived rats decapitated at various times of the day. Blood and tissue hormone concentrations were mea

Recovery of the hypothalamo-pituitary-adrenocortical axis in the rat after long-term dexamethasone treatment

Male rats were treated for 14 days with dexamethasone (2.6 mumol/l in the drinking water) and killed at various times after withdrawal of the drug. Some animals were subjected to stress (ether or sham adrenalectomy) just before killing. The recovery of responsiveness of the components of the hypothalamo-pituitary-adrenocortical axis was assessed by measuring plasma and tissue concentrations of hormones, and the response of the tissue in vitro to appropriate stimuli. In vitro, bioactive corticotrophin-releasing factor (CRF) release in response to acetylcholine and adrenal corticosterone release in response to adrenocorticotrophin (ACTH) were significantly suppressed until 3 days after withdrawal. However, release of immunoreactive or bioactive ACTH in response to ovine CRF or hypothalamic extract did not return to normal until day 5. This was correlated with a reduction in pituitary immunoreactive ACTH content and bioactive plasma ACTH, which were suppressed until days 5 and 4, respectively. No change in hypothalamic immunoreactive CRF content could be detected after treatment, or after stress (ether or sham adrenalectomy) in either treated or control animals. Stress (ether) had no effect on the subsequent response of the anterior pituitary gland in vitro to ovine CRF. The large rises in plasma ACTH and adrenal corticosterone measured after stress (ether) in control animals were completely abolished after dexamethasone treatment and did not return to control values until 5 days after withdrawal. Therefore, it appears that after cessation of chronic dexamethasone treatment in the rat, the responsiveness of the hypothalamus and adrenal gland return to normal before that of the pituitary gland.

Diurnal variations in responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis of the rat

Hypothalami, anterior pituitary gland segments and adrenal glands were removed from female Wistar-derived rats decapitated at various times of the day. Blood and tissue hormone concentrations were measured and the tissues challenged with appropriate stimuli in vitro. Both bioactive and immunoreactive corticotrophin-releasing factor (CRF) content of the hypothalami were significantly higher in the evening than in the morning, as was the basal release of bioactive CRF in vitro. The response of the hypothalami to serotonin or acetylcholine added in vitro did not change with time of day. Basal bioactive and immunoreactive adrenocorticotrophin (ACTH) release from the anterior pituitary gland was significantly increased in the evening, as was the response to synthetic ovine CRF in vitro. Plasma ACTH concentrations in intact rats given crude CRF (hypothalamic extract) in vivo were higher in the evening at all times after injection tested, but this difference was markedly reduced in animals with mediobasal hypothalamic lesions. Corticosterone released basally from adrenal glands in vitro was significantly increased in the evening and the response to added ACTH 1-24 was slightly enhanced. For adrenal glands removed from lesioned rats, the pattern was reversed, corticosterone release in vitro being lower in the evening for all doses of ACTH added. Similarly in vivo, in intact rats given ACTH 1-24, plasma corticosterone concentrations and corticosterone release in vitro from adrenal glands removed after the injection were higher in the evening. After the placement of basal hypothalamic lesions, the situation was reversed, the response to ACTH administration in vivo being greater in the morning.(ABSTRACT TRUNCATED AT 250 WORDS)