Gonad-Brain Relationship: Precocious Brain Maturation After Estradiol in Rats1

Abstract
Effects of estradiol administration on infant rats were studied in relation to brain maturation as measured by electroshock seizure responses. Estradiol dipropionate (100 μg/100 g of body wt) was injected daily into newborn rats for 4 consecutive days, beginning on days 4, 6, 8, 10 and 12. Electroshock was administered during infancy on alternate days until the adult pattern was established, and weekly thereafter. All rats were weighed frequently, sacrificed at approximately 70 days of age, and weights of pituitary, ovaries, adrenals and thymus were determined. After a supramaximal electroshock, the infant rat passes through a successive series of responses prior to showing the mature seizure pattern. The present results showed that all phases of response to electroshock appeared at a significantly (t-test) earlier date in the treated animals than in the controls. Similarly, estradiol induced the precocious appearance of the adult pattern of maximal seizures. Acceleration of brain development appeared to be age-dependent: long-lasting effects upon seizure responses were observed when estradiol was injected from days 6–10 and 8–12. These responses consisted of shortening of tonic flexion and lengthening of tonic extension, which persisted for about 7 weeks and which indicated an increased excitability in the animals. Longterm effects of estradiol were evidenced by significant inhibition of body growth, pituitary hypertrophy, ovary and thymus atrophy and retardation of complete vaginal opening. It is suggested that estradiol administered at a specific time to newborn rats produces longlasting effects on brain maturation, on convulsive responses to electroshock, on body growth and on some endocrine functions.