The effect of betamethasone on circadian and stress‐induced pituitary‐adrenocortical function in the rat

Abstract

Summary Both the circadian and stress‐induced changes in plasma corticosterone concentration were abolished by the inclusion of betamethasone in the drinking water of rats. Adrenal sensitivity to exogenous corticotrophin (ACTH) was unimpaired by the betamethasone treatment. The normal circadian rhythm in plasma corticosterone returned within 1 day of withdrawal of the steroid, but the response to stress was normal only after 3 days. The possible significance of these observations is discussed.

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

“…Acute oral administration of high doses of corticosteroids to guinea-pigs and rats has been reported to leave adrenal sensitivity to ACTH unaffected immediately after the treatment (Purves & Sirett, 1965;Hodges & Mitchley, 1970c;Hodges & Hotston, 1971). However, the present work suggests that there is a reduction in adrenal activity since 48 h after overnight treatment with betamethasone, despite the hypersecretion of ACTH which then occurs, there is no concomitant rise in plasma corticosterone concentration.…”

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

“…Although there may be some adrenocorticotrophic activity associated with the resumption of normal basal steroid concentrations and some circadian variation, normal HPA function may still be impaired (Livanou, Ferriman & James, 1967). Certainly the mechanisms controlling ACTH release differ in their sensitivity to the inhibitory effects of corticosteroids (Hodges & Mitchley, 1970a). …”

“…The circadian rhythm in plasma corticosterone concentration was also studied as described by Hodges & Mitchley (1970a). Corticosterone production by the adrenal glands in vitro was measured using the method of van der Vies, Bakker & de Wied (1960), modified by Flack (1970).…”

The influence of corticosteroids on the secretion of corticotrophin and its hypothalamic releasing hormone

“…This discrepancy may be due to differences in the sensitivity and precision of the assay methods employed. It has been shown before that the stress-induced release of ACTH from the adenohypophysis may be influenced by chronic changes in the level of circulating corticosteroids (Hodges & Jones, 1964;Hodges & Mitchley, 1970b) but is independent of the plasma corticosteroid concentration at the time of the stress (Smelik, 1963a, b;Hodges & Sadow, 1967;Buckingham & Hodges, 1974) and the present data are in accord with the hypothesis that the corticosteroids exert a delayed regulatory effect on the secretion of ACTH in response to stress (Smelik, 1963a). Many studies involving both in vivo and in vitro techniques indicate that corticosterone-sensitive receptors are present in the adenohypophysis (Fleischer & Rawls, 1 970a, b;Watanabe, Nicholson & Orth, 1973;Buckingham & Hodges, 1977a;Jones, Hillhouse & Burden, 1977;, the hypothalamus (Feldman,Conforti & Chowers,339 1973; Vermes, Smelik & Mulder, 1976;Hillhouse & Jones, 1976;Buckingham & Hodges, 1977b;Mahmoud & Jones, 1977;Vermes, Mulder & Smelik, 1977) and a variety of centres higher in the brain (McEwen, Weiss & Schwartz, 1970;Feldman, 1973) (Hillhouse & Jones, 1976;Yasuda & Greer, 1976) Mahmoud & Jones (1977).…”