George H. Greeley

The effect of castration, thyroidectomy and haloperidol upon the turnover rates of dopamine and norepinephrine and the kinetic properties of tyrosine hydroxylase in discrete hypothalamic nuclei of the male rat

Adult male rats were either castrated, thyroidectomized, or treated with haloperidol and the rates of turnover of dopamine (DA) and norepinephrine (NE) in the median eminence (ME), the arcuate and dorsomedial nuclei of the hypothalamus were estimated from the rate of decay of DA and NE concentrations as determined by radioenzymatic assay following blockade of catecholamine synthesis by alpha-methyl-p-tyrosine. The ME of animals similarly prepared was also examined for changes in the total activity and kinetic properties of tyrosine hydroxylase (TH). Four days following the administration of haloperidol (400 microgram/kg) or 10 days after castration, there was a significant increase in the rate of turnover of DA but not NE in the ME accompanied by an increase in the Vmax but not Km for the substrate or cofactor of TH. Furthermore, the administration of haloperidol to hypophysectomized rats also significantly increased the TH activity in the ME, indicating that such changes may occur independently of any changes in serum prolactin levels. Ten days after thyroidectomy, or three weeks after treatment with prophylthiouracil, there was a significant increase in the turnover rate of DA in both the ME and dorsomedial nucleus but not in the arcuate nucleus. No changes in the turnover rates of NE in any of the three areas were observed following thyroidectomy. In the ME, the increase in turnover of DA was accompanied by an increase in the total TH activity (Vmax) as welll as a decrease in Km for tetrahydrobiopterin but not tyrosine. From these results 4 conclusions were drawn: (1) following halperidol, castration, and thyroidectomy there are increases in the activity of dopaminergic terminals within the ME; (2) castration, haloperidol and thyroidectomy may influence the activity of dopaminergic terminals within the ME by different mechanisms; (3) changes in tyrosine hydroxylase and turnover of catecholamines within the ME may occur independently of changes in prolactin levels; and (4) local recurrent afferent circuits may exist in the arcuate nucleus region of the hypothalamus.

Studies of the neural mechanisms by which hypothyroidism decreases prolactin secretion in the rat

These studies report that chronic hypothyroidism in the rat is accompanied by decreased serum prolactin. An investigation of those mechanisms by which hypothyroidism decreases prolactin secretion revealed the following findings: (1) activation of tyrosine hydroxylase in the median eminence (ME) and increase in the turnover-rate of dopamine (DA) in the ME; (2) a decreased content and in vitro release of prolactin by pituitaries from hypothyroid rats; (3) decreased [3H]spiroperidol binding to pituitary homogenates obtained from hypothyroid rats, and (4) normal increase of serum prolactin following administration of haloperidol. Comparison of the effects of hypothyroidism on dopaminergic terminals of the striatum with those of the ME was made and the following tentative conclusions proposed. Hypothyroidism presumably increases the release of DA into the pituitary portal system. A deficiency of thyroid hormone desensitizes the pituitary lactrotrope to inhibition by DA, decreases the total pituitary prolactin content and presumable also reduces the peripheral catabolism of prolactin. The overall net effect of hypothyroidism is, therefore, a decrease in serum prolactin levels which can increase normally following haloperidol. The mechanism by which a deficiency of thyroid hormone alters the function of the tuberoinfundibular and striatal dopaminergic systems is unknown.

Serum thyroxine, triiodothyronine, and TSH levels and TSH release after TRH in aging Male and female rats

Serum levels of TSH, T3 and T4, pituitary responsiveness to TRH, and T3-resin uptake were examined in aging male and female rats. Despite normal serum TSH levels, serum T3 and T4 levels were significantly reduced in old male rats (19-26 months of age) when compared to young (120-150 days of age) and middle-aged males (12-1- months of age). In old female rats, serum TSH and T3 levels were not significantly (p greater than 0.05) different from those of young or middle-aged females. Serum T4 levels were significantly lower in old females when compared to younger rats. The T3-resin uptake of old rats was not significantly different from the value of young rats. Serum T4 levels, 3 hours after TRH induced TSH release, were significantly depressed in old male and female rats. Pituitary sensitivity to TRH was unaltered in old rats. These findings suggest that thyroidal release of T4 and T3 is depressed, and that the hypothalamic-pituitary axis is insensitive to diminished thyroid hormone feedback in old rats.

A delayed LH/FSH rise after gonadectomy and a delayed serum TSH rise after thyroidectomy in monosodium-l-glutamate (MSG)-treated rats

The serum LH and FSH rise after gonadectomy and the serum TSH rise after thyroidectomy were examined in rats that received monosodium-L-glutamate (MSG) as neonates. The rise in serum gonadotrophins after gonadectomy was significantly delayed in both adult and peripubertal MSG-treated rats when compared to control castrates. Serum LH and FSH levels, however, eventually achieved levels in MSG-treated rats that were not significantly different than those of controls. The serum TSH rise after thyroidectomy was significantly delayed in adult female MSG-treated rats, but not in prepubertal female MSG-treated rats. Pituitary responsiveness to both exogenous LH-RH and TRH was unaffected by neonatal MSG treatment, with one exception: pituitary responsiveness to HL-RH of orchidectomized peripubertal males was blunted significantly. The results are discussed in terms of the possible neurotoxic effects of neonatal MSG treatment, as well as the altered hypothalamic sensitivity to gonadal steroids.