Some physiological, biochemical, and behavioral consequences of neonatal hormone administration: Cortisol and thyroxine

The presence of specific hormones in excess of ontogenetically inappropriate times during development may compromise the capability of certain adaptive or survival value mechanisms at later stages of the life cycle, as well as provide for the later full expression of these adaptive mechanisms.

Abstract

Excess cortisol or thyroxine was administered to infant rats and various biochemical, physiological, and behavioral observations were made on the young and adult animal. A single injection of cortisol into the 1-day-old rat produced a complex of developmental abnormalities including decreased brain cholesterol, locomotor activity, body weight and delayed ontogeny of cerebral cortical dendritic spines. As adults, the hormone-treated rats produced less antibodies in response to the immunological challenge of two different antigens. The most severe and clinically relevant effect was an impairment in adult immunological responsiveness to antigenic challenges Neonatal thyroxine administration for several days immediately after birth did not cause the expected increase in oxygen consumption. The eyes of the treated animals opened earlier than littermate controls, brain cholesterol was increased, and the animals exhibited greater spontaneous locomotor activity. The activity of acetyl-cholinesterase in the hypothalamus and cortex was increased when measured 10 days after hormone administration was discontinued. Brain α-glycerophosphate dehydrogenase induction was unaffected by thyroxine at any age. The liver enzyme was increased, however, by hormone administration at all ages from fetal life to adulthood. The onset of physiological and behavioral bio-environmental interaction was accelerated: The maturation of the pituitary-adrenal response to stress appeared earlier; the development of the cortical EEG was advanced, as was its response to novel stimuli. This appeared to correlate with the earlier appearance of the startle reflex in the thyroxine treated animals. Young thyroxine-treated rats of 16, 17, and 18 days of age learned to avoid an electric shock faster than controls. However, when the experimental animals are adults they make more errors on two different maze-learning tasks. These results suggest that: (1) The presence of specific hormones in excess of ontogenetically inappropriate times during development may compromise the capability of certain adaptive or survival value mechanisms at later stages of the life cycle. (2) The immature status of some neuroendocrine systems during such hormone sensitive periods may therefore provide for the later full expression of these adaptive mechanisms.