Testicular inhibition of tyrosine hydroxylase expression in tuberoinfundibular and nigrostriatal dopaminergic neurons

We have investigated, in young and aged rats, tuberoinfundibular dopaminergic (TIDA) and nigrostriatal neurons of the brain, and the role of the testes and anterior pituitary (AP) on 1) the in situ activity of tyrosine hydroxylase (TH), 2) translation of TH mRNA, as reflected by the mass of TH, and 3) transcription of the TH gene, as revealed by the mass of TH mRNA. The median eminence (ME) and corpus striatum (CS) were used as the sources of proximal neurites of the TIDA neurons and nigrostriatal neurons, respectively. The arcuateperiventricular nuclei of the ventral hypothalamus were used as the source of perikarya of the TIDA neurons, and substantia nigra (SN) nuclei of the midbrain were used as the source of perikarya of nigrostriatal neurons. The in situ activity of TH was calculated using the rate of accumulation of dihydroxyphenylalanine after pharmacological inhibition of dihydroxyphenylalanine decarboxylase activity. TH mass and TH mRNA were measured using an immunoblot assay and an S1 nuclease protection assay, respectively. Compared to intact animals, orchidectomized young and aged male rats had significantly (P < 0.001) increased in situ activity of TH in the ME and CS, but not the SN. Orchidectomy also caused a significant (P < 0.01) increase in the quantity of TH in the ME and a 2- to 3-fold increase in TH in the CS and SN. In contrast to castration, AP grafts, implanted in the lateral ventricles of the brain, caused a significant (P < 0.001) increase only in TH activity in the ME. No effect of AP grafts was seen on TH activity of the CS or SN. AP grafts had no effect on the amount of TH in the ME, CS, or SN. In the TIDA neurons of young males and in the nigrostriatal neurons of young and aged castrates, the amount of TH mRNA was not different from that in intact males. AP grafts had no effect on TH mRNA in these dopaminergic neurons. These studies show that TIDA neurons and nigrostriatal neurons share some common aspects in their regulation and are dissimilar in others. AP grafts stimulate TH activity in young as well as aged TIDA neurons, but not in nigrostriatal neurons. Castration leads to an increase in TH mass in both TIDA and nigrostriatal neurons. The increase in TH mass is not associated with an increase in the amount of TH mRNA. It is suggested that castration results in increased translation of TH mRNA, but not transcription of the TH gene. We propose that a hormone(s) from the testes suppresses biosynthetic processes in dopaminergic neurons of the young and aged brain.