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.
D000818:Animals; D002369:Castration; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008473:Median Eminence / Q000201:enzymology; D008781:Methyltyrosines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D013965:Thyroidectomy; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D008781:Methyltyrosines; D011441:Propylthiouracil; D014446:Tyrosine 3-Monooxygenase; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine