Effect of Neonatal Hydrocortisone on Corticosteroid Circadian Periodicity, Responsiveness to ACTH and Stress in Prepuberal and Adult Rats

Abstract

500 µg hydrocortisone acetate was administered subcutaneously to 2-day-old male and female rats. Study of these animals at 30 days of age revealed virtual obliteration of the circadian periodicity of plasma corticosteroid levels, but preservation of normal adrenal responsiveness to ACTH and to the stresses of immobilization and etherization. Circadian periodicity was normal in both male and female animals studied at 80 days of age. The other cited parameters were tested only in male animals at this age, and again were found to be normal. These studies indicate (1) a dissociation between the effects of neonatal corticosteroid administration on corticosteroid periodicity and corticosteroid responsiveness to ACTH and stress; and (2) the lack of permanence of the effects on corticosteroid periodicity.

Effects of Neonatal Hydrocortisone Treatment on Pituitary and Adrenocortical Response to Stress in Young Rats

“…The data show further that the ACTH response to stress is suppressed in a dose-dependent fash ion, the greater suppression occurring in ani mals treated with the larger dosage. While we did not measure corticosterone levels through out the period following the neonatal hydro cortisone injection on day 1, Krieger [13] re ported that 0.5 mg of hydrocortisone admin istered on day 2 elevated plasma corticoste rone levels above that of saline-injected con trols for 48 h. The present effects may be the result of varying lengths of exposure to hydro cortisone resulting from differential rates of clearance at each dosage level. None of the doses of hydrocortisone appeared to abolish completely the release of ACTH following stress, since stress levels in all animals were elevated over baseline values of untreated con trols.…”

“…Several studies have reported increased adrenal weights (mg/ 100 g b.w.) in hydrocortisone-treated animals [13,21], and either decreased [13,29] or in creased [13] adrenal response to stress or ACTH. The site of the CNS-pituitary-adrenal lesion in steroid-treated animals has not been determined.…”

“…data]. The corti costerone response to stress beyond 30 days of age has not been demonstrated to differ from control levels [13,15,17,21], although suppression below control levels has been noted at 20 days of age [29]. Several studies have reported increased adrenal weights (mg/ 100 g b.w.)…”

“…Proliferation of dendritic spines [27] is delayed, development of the blood brain bar rier is retarded, and the developmental rise of brain serotonin is slowed [32]. Changes lasting until adulthood include impaired immuno logical response to some antigens [24], a re duction in body weight [9,13,18,22], and a reduction in brain size and DNA con tent [9],…”

“…Several studies have shown that in jections of corticosteroids within 3-4 days af ter birth delay the onset of the diurnal rhythm of plasma corticosterone from its normal ap pearance about the time of weaning [1,2,19] to as much as 55 days of age [3,12,13,17,28,29], Injections of ACTH on days 7-9 or 17-19 resulted in damped diurnal excursions of cor ticosterone as late as 120 days of age [15]. Hydrocortisone-treated animals are more sen sitive at 23-25 days of age to feedback inhibi tion of ACTH by both corticosterone and dexamethasone than are vehicle-treated con trols [Erskine et al, unpubl.…”