Dexamethasone and Corticosterone Administration to Pregnant Rats: Effects on Pituitary-Adrenocortical Function in the Newborn

Abstract

Although there is convincing evidence that the fetal pituitary-adrenocortical system of the rat is fully operative in late stages of gestation, the question of whether maternal corticosteroids traverse the placenta to influence fetal hypophyseal function has not been satisfactorily resolved. Enlargement of the fetal adrenal occurs if pregnant rats are either adrenalectomized (1-3) or treated with adrenocortical inhibitors (4, 5). Administration of cortisone to either intact or adrenalectomized pregnant rats causes reduction in fetal adrenal weight (1, 6) and compensatory hypertrophy of the remaining adrenal following fetal unilateral adrenalectomy is inhibited by injections of cortisone or hydrocortisone to the fetus (6-8). Knobil and Briggs ( 2 ) , however, reported no increase in fetal adrenal weight if pregnant rats were hypophysectomized prior to adrenalectomy and concluded that the fetal adrenal hypertrophy reflects increased maternal rather than fetal ACTH secretion. Others have demonstrated that stimulation of the maternal adrenal (by cold or with exogenous ACTH) suppressed rather than stimulated fetal adrenal function and these investigators (9) maintain that maternal corticosteroids, but not ACTH, are capable of crossing the placenta. I t is alleged (10) that the source of the relatively high plasma corticosterone levels found in newborn rats is the fetal adrenal itself but other investigators maintain that maternal corticoids normally traverse that placenta at term to exert a restraining influence on fetal ACTH secretion ( 1,6! 11 ) .The possibility that placental transmission 1Supported by Grant .4M-00432 and a Career Research Award (NB-K6-18,536) given to Dr. S. A. D'Angelo by the NIH.of maternal corticoids may result in inhibition of ACTH secretion by the fetal hypophysis has close relevance to accurate interpretation of early postnatal changes which occur in the rat's pituitary-adrenocortical axis. The adrenal gland fails to respond to certain noxious stimuli in early postnatal life. I t is not yet clear whether this ''stress nonresponsive" period ( 1 2 ) in the neonate is due to immaturity of the pituitary ACTH secretory mechanism (13), failure of CRF release from the hypothalamus ( 10) ' or prolongation of corticosterone negative feedback potency on brain and/or pituitary (14). Whether or not it may also reflect a new set of hormonal conditions imposed by the external environment remains to be determined. The present study was directed toward elucidation of this problem by ascertaining the status of ACTH secretion and adrenal function in the newborn of intact and hypophysectomized pregnant rats administered dexamethasone or corticosterone during the last several days of gestation. The results obtained are consistent with the hypothesis that deficiency or excess of circulating levels of adrenocorticoids in the mother induces significant change in ACTH secretion by the fetal pituitary.Materials and methods. Timed-pregnan t rats of the CD strain (Sprague-Dawley derivatives) were supplied by the Charl...

Inhibitory effects of adrenocorticotrophin or corticosterone on progesterone secretion during mid-pregnancy in rats

“…After Day 18, however, corticosterone concentrations in the maternal circulation were directly related to the conceptus number (Dupouy et al, 1975) It has been reported that the fetus participates in the regulation of luteal function (Kittinger et al, 1980). In the present study, ACTH treatment reduced the weights of the fetus and placenta (Table 1), which confirmed the previous report for mice (Paul & D'Angelo, 1972). There are several reports that adrenalectomy or corticoid treatment of the mother affect fetal adrenal function (Knobil & Briggs, 1954;Baldwin, 1979).…”

Modification of pituitary-adrenal feedback sensitivity in young rats by neonatal treatment with cortisol

“…Physiological levels of exogenously administered corticosterone have been shown to inhibit the sub¬ sequent pituitary-adrenal response to stress in adult rats (Zimmerman & Critchlow 1969;Jones & Tiptaft 1977) and feedback inhibition of ACTH by corticosteroids also appears to occur in the perina¬ tal period (Paul & D'Angelo 1972;Milkovié et al 1976). However, studies of feedback inhibition during the period between weaning and puberty have yielded conflicting results.…”