Rats were injected with monosodium 1-glutamate (MSG) daily for the 1st 5 days of life and allowed to mature. This is known to cause selective destruction of neurons in the retina and in the arcuate nucleus of the hypothalamus. The adult animals had a significant increase in body fat without an increase in weight, a marked reduction in pituitary, thyroid, adrenal, gonadal and prostate weights. Pituitary, hypothalamic and serum thyrotropin (TSH) were significantly reduced in the males. Serum growth hormone (GH) was markedly reduced in both sexes and the serum prolactin (Prl) was increased significantly in females. FSH did not appear to be abnormal and the LH may have been increased in the males. Serum T₄ was significantly reduced in females. The fertility of the females was normal, but treated males mated with normal females showed a marked reduction in fertility and, although the litter sizes of the offspring were normal, the birth weights of the pups of both sexes were significantly reduced. These persistent alterations in neuroendocrine function indicate that lesions produced by neonatal MSG treatment provide a convenient model for studying hypothalamic function.

1Serum and CSF samples of patients receiving chronic carbamazepine treatment were analysed. 2 Daily fluctuations in serum levels of carbamazepine and carbamazepine-10, 11-epoxide did not appear to be related to the dosage schedule, but some patients tended to have lower fluctuations when the carbamazepine was given more frequently. 3 The epoxide/carbamazepine serum ratios varied greatly from patient to patient, and also fluctuated during the day for the same patient. 4 Carbamazepine and carbamazepine-10,11-epoxide were present in CSF in concentrations ranging from 19 to 34% and 26 to 71 % of the serum concentrations, respectively.5 There was a significant relationship between the free fraction of both drugs evaluated in vivo and the CSF/serum ratios. 6 The need for a careful evaluation of the possible clinical effect of the epoxide is stressed.

Rats treated during the first 5 days of life with pharmacologic doses of thyroxin (T 4 ) subsequently develop a variety of persistent endocrine abnormalities which are designated the "neo-T 4 syndrome." In the present experiments the rats treated neonatally were smaller and their pituitary, thyroid, adrenal, testicular and ventral prostate weights were decreased. Their plasma TSH concentration was reduced, the metabolic clearance rate of exogenous TSH was normal, and the calculated basal TSH secretion rate was reduced from 30.2 ± 3.3 /xU/min to 19.7 ± 1.4. In four different experiments to test the response to thyrotropin-releasing hormone (TRH) stimulation there was a subnormal secretion of TSH in rats with the neo-T 4 syndrome. The TRH content of the hypothalami from the neo-T 4 treated rats was measured by radioimmunoassay and found to be unexpectedly and significantly elevated from a mean control value of 5.58 ± 0.12 ng/ hypothalamus to 7.12 ± 0.39 ng. It is concluded that the reduction in circulating TSH in the neo-T 4 syndrome is not mediated by alterations in TSH metabolism but is secondary to subnormal pituitary responsiveness to TRH, possibly associated with a chronic deficiency of TRH secretion. (Endocrinology 95: 406, 1974)

Rats made thyrotoxic with large doses of thyroxine (T4) during the neonatal period (neo-T4) show many abnormalities as adults. These usually include impaired body, pituitary and thyroid growth, diminished pituitary and serum TSH concentrations, a diminished serum T4 and a diminished response to PTU challenge and to thyrotropin-releasing hormone (TRH) stimulation. Experiments are presented which show that these rats are hypersensitive to feedback regulation by T4 in a manner similar to that seen after bilateral anterior hypothalamic lesions. They show a subnormal response to PTU challenge and an excessive suppression of serum TSH and goiter growth after T4. Pituitary TSH was less depleted in neo-T4 rats when a small dose of T4 was given daily with PTU and pituitary TSH was more sensitive to suppression by a larger dose of T4 in the neo-T4 group. There was an impaired rebound increase in pituitary TSH following a single inhibitory dose of T4 injected into the adult hypothyroid rat. Although the hypothalamic TRH content is increased in the neo-T4 rat, the circulating concentration of TRH was found to be significantly decreased, supporting the theory that the defects observed in the neo-T4 rat may be the consequence of an impaired hypothalamic secretion of TRH.