Studies on the effect of neonatal hypermetabolism on hypothalamo-pituitary-thyroid axis in adult rats.

Neonatal rats which had received a daily injection of 50 microgram of 2,4-dinitrophenol (DNP) or 30 microgram of L-thyroxine (T 4) for 7 days beginning on the day of birth were compared as to the late effect of the hypothalamo-pituitary-thyroid axis with the neo saline control. Neo DNP rats and neo T 4 rats revealed the retardation of growth compared with neo saline rats. The plasma level of TSH in both groups presented its low response following TRH administration. Furthermore, plasma TSH levels following the challenge of PTU were depressed in both neo DNP and neo T 4 rats compared with neo saline control rats. A small dose of T 4 injection, however, did not bring any difference on plasma TSH levels between neo T 4 and neo saline control rats while neo DNP rats showed a little blunted response of pituitary compared with neo T 4 and neo saline rats. Pituitary contents of TSH in neo T 4 rats decreased, but not in neo DNP rats. These results suggest that neonatal hypermetabolism causes the hypofunction of pituitary-thyroid axis through adult life and that the alteration of hypothalamus may be more obvious in neo T 4 rats than in neo DNP rats.     

The effect of propylthiouracil and temperature on avian thyroid activity.

High ambient temperatures cause a reduction in thyroid gland size of chickens but propylthiouracil (PTU) treatment produces an increase in gland size regardless of temperature. This increase in size after PTU treatment during high temperature is evident after 7 days of PTU treatment but not after 14 days of treatment. Cyclic AMP-dependent protein kinase is activated in the thyroid gland with PTU treatment during high temperatures with no alteration in activity in the pituitary. These results suggest that the pituitary is not activated by TRH during periods of high ambient temperature and the thyrotrophs may release TSH in direct response to lowered serum thyroid levels produced by PTU treatment.     

Ultrastructural changes in the rat thyroid gland during iodine deficiency

Thyroid ultrastructure changes were studied during the course of a low iodine diet in rats. At day 20, follicles were normal, but a number of them contained cells of higher density and with greatly elongated microvilli. Endoplasmic reticulum cisternae were frequently dilated. From day 20 until day 80, the most characteristic changes in the thyroid cells were the progressive accumulation of subapical peroxidase-positive exocytotic vesicles. After 80 days of the low iodine treatment, Golgi apparatuses were very active. Cell division could be observed. At this stage, exocytotic vesicles were generally very abundant. These data suggest that the remarkable accumulation of subapical exocytotic vesicles between day 20 and day 120 might represent an adaptation to the moderate and gradual increase in TSH stimulation that occurs in the conditions of low iodine diet.     

Effect of neonatal testosterone and oestradiol treatment on the development of the hypothalamo-hypophysial axis in the female rat.

The hypothalamic LH-RH content and the concentrations of pituitary and plasma LH were measured at various ages in female rats treated daily with 10 micrograms testosterone propionate or 10 micrograms oestradiol-17beta from birth to Day 15. Persistent vaginal oestrus was induced in all the treated rats. Both hormones significantly reduced the hypothalamic LH-RH content and pituitary and plasma LH concentrations. Hypothalamic LH-RH increased after cessation of treatment but pituitary LH did not return to normal levels. Plasma LH levels were significantly lower than those in control rats. It is concluded that testosterone propionate and oestradiol-17beta (1) have a direct negative feed-back influence on the hypothalamus in the neonatal female rat; (2) alter the normal pattern of plasma and pituitary LH in developing female rats; (3) prevent the cyclic secretion of plasma LH after maturity; and (4) probably cause a chronic impairment in the release of LH-RH.     

Effect of propylthiouracil and thyroxine on the inactivation of somatostatin by rat hypothalamus.

The inactivation of somatostatin by hypothalamic and brain extracts were studied in rats treated with propylthiouracil (PTU) alone or with PTU and thyroxine. 90 days after the onset of treatment with PTU, the potency of hypothalamic extract to inactivate somatostatin was increased almost 2-fold; while no change was observed for brain extract. Thyroxine reversed the enhancing effect of PTU on the activity of the enzyme(s) degrading somatostatin. A pH study shows that both brain and hypothalamic enzymic systems are different. These data suggest that the inactivation process of somatostatin by hypothalamic extract could be an important factor in the regulation of the hypothalamic-hypophyseal thyroid axis in rat.     

The effect of total parenteral nutrition (TPN) on the enteroinsular axis in the rat

The effect of 6 days of total parenteral nutrition (TPN) on the enteroinsular axis was studied in vivo and in vitro in the rat. During the TPN period, blood samples were taken from control and TPN animals to determine the comparative pattern of GIP release. Glucose, insulin and GIP responses to oral glucose (OGTT) were compared in TPN and control rats. The effect of glucose and GIP on insulin release from the isolated perfused pancreas of the same animals was investigated to determine if TPN altered the sensitivity of the beta cell. In conjunction with these studies the number and distribution of GIP-containing cells were compared in control and TPN animals. TPN resulted in no change in basal levels of glucose, insulin and IR-GIP. An exaggerated insulin response to OGTT occurred after TPN whereas the glucose response was reduced. The IR-GIP response to glucose was normal following TPN. The isolated perfused pancreas showed a 30% increase in insulin release in response to GIP after TPN. The insulin response to glucose appeared normal as did the number and distribution of GIP cells. Fluctuations in GIP and insulin levels in control animals were diurnal in nature, whereas IR-GIP levels in TPN animals remained near fasting levels. It was hypothesized that the increase in beta cell sensitivity to GIP may be causally connected to the exposure of the pancreas to chronically low levels of GIP during TPN.     

Effect of neonatal thiamine and vitamin A deficiency on rat brain gangliosides

Effects of neonatal thiamine deficiency and vitamin A deficiency on total and fractions of gangliosides (GT1, GD1a, GD1b and GM1) were studied in Charles Foster rat brain at 21 days of age. GT1, GD1b+GD1a and GM1 are being presented here as poly-, di- and mono-sialo gangliosides. Thiamine and vitamin A deficiencies were induced by feeding mothers essentially thiamine and vitamin A free diets respectively. A normal control (G+L+) and weight matched undernourished groups (G+L- for thiamine and LL for vitamin A experiments) were used for comparison. At 21 days, the concentration of total gangliosides in thiamine deficient and G+L- rat brains were 49.0% and 45.7%; in vitamin A deficient and LL group were 66.6% and 88.0% of the G+L+ group, respectively. The percent contribution of poly-, di- and mono-sialo gangliosides in G+L+/thiamine deficient/G+L- were; 17.2/46.8/73.5, 54.4/51.7/14.2, and 6.6/8.7/5.8, respectively. The percent contribution of poly-, di- and mono-sialo gangliosides in G+L+/vitamin A deficient/LL were; 19.3/39.9/43.7, 57.0/37.6/35.1, and 8.4/11.6/19.7 respectively. The changes observed in these experiments suggest an underlying possibility of metabolic defect in undernourished animals.     

The effect of neonatal thymectomy on antibody responses to histocompatibility antigens in the rat

Neonatally thymectomized rats produced alloantibody of only the IgM class in response to histocompatibility (H) antigens governed by the major H locus. They produced no antibody against minor H antigens. Unaltered rats produced only IgG antibody against minor H antigens and this response is therefore termed T cell obligatory. This is in distinction to the T cell-dependent response of unaltered rats to major H antigens, which is composed of an initial IgM component followed by conversion to production of IgG.     

The effect of vitamin A deficiency on hepatic, renal and pulmonary glutathione S-transferase activities in the rat.

Feeding male weanling rats on a vitamin A-deficient diet for 6 weeks resulted in significant increases (44-57%) in glutathione S-aryl-, S-aralkyl- S-alkyl- and S-epoxidetransferase activities in the liver cytosol. Only the S-aralkyl- (27%) and S-alkyltransferase (14%) activities were significantly increased in the kidney as a result of deficiency. There was no effect on any of the pulmonary glutathione S-transferase activities. The increases in hepatic transferase activities were due primarily to increases (25-96%) in the apparent Vmax. There were no changes in the apparant Km of any of the four drug substrates employed. With 3,4-dichloronitrobenzene as the second substrate, the apparent Km for glutathione was increased by over 2-fold in vitamin A-deficient livers as compared with controls. The relationship between these results and enhanced susceptibility to chemical carcinogens in vitamin A deficiency is briefly discussed, and comparison is made between the effects of this nutritional state and pretreatment with drug inducers on the glutathione S-transferases.