Lack of hypertrophy of the adrenal in exencephalic fetal rats subjected to hypervitaminosis A and then to maternal adrenalectomy.

Abstract

Mother rats were treated daily with 30,000 USP units of vitamin A on the 8th, 9th and 10th days of gestation. Subsequently, some of them were adrenalectomized on the 20th day of gestation or were subjected to laparotomy for the injection of 1 IU of ACTH to each exencephalic fetus on the 21st day of gestation. Autopsy was performed on the 22nd day of gestation. Maternal hypervitaminosis A induced exencephaly in some fetuses in which the growth of the adrenal was retarded despite the presence of the anterior pituitary. Maternal adrenalectomy did not cause a significant hypertrophy of the fetal adrenal in exencephalics but did in non-exencephalics in the same litter. The adrenals of exencephalics given ACTH were enlarged significantly. The observations suggest that the fetal brain-pituitary region plays an essential role in the mechanism of hypertrophy of the fetal adrenal following maternal adrenalectomy. (Endocrinology 88: 1526, 1971) T ADRENALS of anencephalic or hydrocephalic human fetuses are invariably small, regardless of the presence or absence of the anterior pituitary (1). Similar retardation of the adrenal growth has been observed in fetal rats under various experimental conditions such as complete removal of the hypothalamus by decerebration of a fetus (2), destruction of the fetal hypothalamic area with an electrocoagulator, compression of the fetal brain by intracranial paraffin injection, and induction of fetal exencephaly by hypervitaminosis A (3). These observations suggest that the brain, including the hypothalamus, is necessary for the growth of the adrenal during prenatal life. However, such observations still do not necessarily rule out the possibilities of partial autonomy of the fetal pituitary-adrenal axis or some influence of maternal CRF on the axis. The present studies were carried out to compare the extent of retardation of the adrenal growth in the absence of the pituitary with that which occurs when the brain is defective and to examine to what extent the adrenal of a fetus in which the brain was destroyed could enlarge following maternal adrenalectomy. The defect of the fetal brain was induced by maternal hypervitaminosis A. Materials and Methods Rats of the Wistar strain were used. They were given a commercial diet (Oriental pellets NMF) and water, both ad lib. Days of gestation were counted from the day following an overnight matReceived June 2, 1970. ing, which was counted as the 1st day of gestation. The experimental groups and designs were: Group 1. Mother rats were subjected to midventral laparotomy under ether anesthesia on the 20th day of gestation in order to decapitate surgically 3 or 4 fetuses in utero in each litter by the method of Domm and Leroy (4) for the purpose of hypophysectomy. Two days later, at autopsy, these decapitated fetuses were matched at random with intact litter-mate fetuses of the same sex. Group 2. Mother rats were adrenalectomized on the 20th day of gestation via the dorsolumbar approach. Subsequently, on the same day, they were subjected to laparotomy and 2 or 3 fetuses in each litter were decapitated. Two days later, autopsy was performed. Group 3. Mother rats were treated daily with 30,000 USP units of vitamin A palmitate (Sigma Chemical Co.) suspended in 0.6 ml of saline by a stomach tube on the 8th, 9th and 10th days of gestation. Autopsy was performed on the 22nd day of gestation. Litters in which all or none of the fetuses showed exencephaly were discarded. In each litter used, exencephalic fetuses were matched at random with non-exencephalic fetuses of the same sex. The remaining odd fetuses were discarded. Group 4. Mother rats were treated with vitamin A as in group 3. They were subjected to adrenalectomy on the 20th day of gestation. Exencephalic fetuses were paired with litter-mate non-exencephalic fetuses in the same way as in group 3. Group 5. Mother rats were treated with vitamin A as in group 3. They were subjected to laparotomy on the 21st day of gestation for the injection of