Recovery of hypothalamo‐pituitary‐adrenal function in the rat after prolonged treatment with betamethasone

Abstract

Summary1. Betamethasone caused growth retardation, adrenal atrophy and impaired hypothalamo-pituitary-adrenal (HPA) activity in the rat. 2. In spite of the profound impairment, recovery of normal HPA function was rapid, but the growth retardation persisted.3. The ability of the pituitary gland to secrete basal corticotrophin (ACTH), recovered more rapidly and the adrenocorticotrophic response to stress less rapidly than the ability of the adrenal cortex to respond to ACTH. 4. The degree of HPA suppression was not determined by the total dose of steroid. 5. The possible significance of the results is discussed.

Caffeine Enhances the Speed of the Recovery of the Hypothalamo-Pituitary-Adrenocortical Axis after Chronic Prednisolone Administration in the Rat

“…The present studies with prednisolone essen tially confirm the previous more extensive studies, in which the recovery of the HPA axis following a variety of dosing regimens with a number of steroids was reported [4][5][6][7][8]. In those studies also a greater number of parameters (including plasma ACTH and corticosterone levels before and after stress and over the 24-hour period, adrenal sensitivity in vivo and in vitro, pituitary ACTH content and sensitivity in vitro, hypothalamic CRF con tent and the ability of the hypothalamus to release CRF in re sponse to different neurotransmitters) were investigated than in the present study.…”

“…In the rat, extensive studies by Hodges and Mitchley [4,5], Buckingham and Hodges [6] and by Nicholson et al [7,8] showed that chronic administration of glucocorticoids for 7-14 days results in a transient suppression of the HPA axis, which is followed by a stage of hyperresponsiveness of the adrenal gland after 5-7 days. The present studies with prednisolone essen tially confirm the previous more extensive studies, in which the recovery of the HPA axis following a variety of dosing regimens with a number of steroids was reported [4][5][6][7][8].…”

“…Dependent on the dose and duration of glucocorticoid administration the recovery of the HPA axis in man may take weeks to months [1][2][3]. Hodges and Mitchley [4, 5], Buckingham and Hodges [6], and Nichol son et al [7, 8] studied the recovery of the HPA axis in the rat after chronic treatment with pharmacological amounts of gluco corticoids. In extensive studies they found that the pattern of recovery of the HPA axis after glucocorticoid administration shows a normalized responsiveness of the hypothalamus and the adrenal gland in vitro within a week.…”

Hypothalamo‐pituitary Adrenocortical Function in the Rat After Treatment With Betamethasone

“…Our rats were given the same total dose of steroid over different periods and different effects on the HPA axis were evident. This confirms earlier studies (Hicklin & Wills, 1968;Hodges & Mitchley, 1970a) but is contrary to the findings of Treadwell, Savage, Sever & Copeman (1963). Prolonged treatment with the lower concentration of the steroid caused only slight suppression of HPA activity.…”

“…The HPA system recovers from corticosteroid-induced suppression in a way which is still not understood despite the existence of data on this aspect of HPA function both in man (Daly, Myles, Bacon, Beardwell & Savage, 1967) and in the rat (Hodges & Mitchley, 1970a). Such studies are often limited by the fact that only indirect indices of pituitary adrenocorticotrophic activity have been used.…”