Neonatal Hyperthyroidism and Maturation of the Rat Hypothalamo-Hypophyseal-Adrenal Axis

Abstract

The neonatal rat exhibits a refractory period of the hypothalamo-hypophyseal-adrenal axis in response to stress which encompasses days 3-1 2 of life, an interval called the stress nonresponsive period (SNR) (1). Then, at 15 days of age, the rat responds equally to ether stress and exogenous ACTH by an increased synthesis and release of corticosterone (2). However, hypothyroidism induced by thiouracil feeding during pregnancy and lactation prevented the hypothalamo-hypophyseal-adrenal axis response to ether stress possibly by extending the SNR period (3). What effect the feeding of desiccated thyroid would have on the maturation of this axis has not been reported. Thus the purpose of the present study was to examine the effect of thyroid feeding on the response of 12-day-old rats to ether stress and to exogenous ACTH by measuring adrenal corticosterone (B) (an index of hormone synthesis) and serum corticosterone (an index of hormone release). Materials and Methods.Female Sprague-Dawley rats weighing 150-175 g (Camm Research Institute, Wayne, NJ) were housed in a temperature (78" F) regulated room with a light-dark cycle of 12: 12 hr. The rats were fed Purina Lab Chow ad lib. until a body weight of 180-200 g was attained. The animals were then mated with proven males of the same strain.

Thyroxine Modulates Corticotropin‐Releasing Factor but not Arginine Vasopressin Gene Expression in the Hypothalamic Paraventricular Nucleus of the Developing Rat

“…We have demonstrated that hyperthyroidism, induced by daily T 4 injection, accelerates the maturation of the HPA axis in the rat during the early postnatal period. After T 4 treatment, our results demonstrate, as previously reported ( 3–5), significant increases in plasma corticosterone concentrations in 8‐ and 15‐day‐old rats. This increase does not seem to be secondary to a direct effect of T 4 at the adrenal gland since, in vivo and in vitro , T 4 decreases corticosterone secretion ( 21).…”

“…This period of development is named the ‘stress hyporesponsive period’, and concentrations of thyroid hormones may participate in this phenomenon. Plasma thyroxine is low at birth, rising to a peak around days 8–12 ( 2), and administration of T 4 enhances basal circulating concentrations of corticosterone during early postnatal life ( 3–5), possibly secondary to a T 4 ‐induced rise in circulating concentrations of corticosteroid binding globulin (CBG) ( 6, 7). In addition, thyroid hormones could modulate the main hypothalamic factors that stimulate ACTH release: corticotropin‐releasing factor (CRF) and arginine vasopressin (AVP) since thyroid hormones exert major influences on rat brain development, differentiation and gene expression ( 8).…”

Thyroid Hormones Influence the Development of Hippocampal Glucocorticoid Receptors in the Rat: A Mechanism for the Effects of Postnatal Handling on the Development of the Adrenocortical Stress Response

“…Thus, neonatal Tj administration re sults in an early increase in basal corticosterone titers and CBG levels [6,10,22] as well as in the early maturation of the adrenocortical response to stress [29]. In contrast, PTU administration during this period delays the maturation of the adrenocortical stress response and suppresses CRF-like activity in the hypothalamus [23,24].…”

Circulating Corticosterone in the Infant Rat: The Mechanism of Age and Thyroxine Effects

“…Specifically, the developmental increase in this parameter was advanced approximately 3 days in hyperthyroid animals and was delayed approximately 3 days in hypothyroid animals. Previous studies on the effects of T4 status on the in vivo response of serum corticosterone to ACTH yielded conflicting results (22)(23)(24) and their interpretation was complicated by the use of a fluorometric assay which is known to be inappropriate in young rodents (1,…”