Effect of cerebroventricular anterior pituitary grafts on in situ expression of tyrosine hydroxylase in dopaminergic neurons of the aged animal.

The effect of cerebroventricular anterior pituitary (AP) grafts on brain tyrosine hydroxylase (TH) expression in the median eminence (ME), substantia nigra (SN), and corpus striatum (CS) has been investigated in young and aged female rats. TH expression was studied using the following indices: in situ TH activity, TH mass, and quantity of TH mRNA. The rate of synthesis of dihydroxyphenylalanine (DOPA) was evaluated by measuring its accumulation in the ME, SN, and CS. TH mRNA and TH mass were quantified by an S1 nuclease protection assay and an immunoblot assay, respectively. Viability of the grafts was demonstrated by histological examination and by their ability to secrete PRL into the cerebrospinal fluid (CSF). Liver grafts served as controls. In castrated young and castrated aged animals with AP grafts, the PRL concentrations in the CSF were 204 +/- 49 (mean +/- SE) and 345 +/- 83 ng/ml, respectively, compared to control values of 14 +/- 9 and 23 +/- 9. In intact aged animals, the concentration of PRL was 729 +/- 180 ng/ml in CSF of rats with AP grafts and 223 +/- 62 ng/ml in the controls. DOPA synthesis in the ME of castrated young rats and castrated aged rats with AP grafts was significantly (P less than 0.01) greater than that in controls with liver grafts. AP grafts did not stimulate DOPA synthesis in the ME of intact aged animals. The synthesis of DOPA in the SN and CS was not affected by AP grafts, regardless of the status of the animal. The amount of TH mRNA and the quantity of TH were not influenced by the AP grafts in any of the animal models. However, the in situ molar activity of TH in the ME was significantly greater in castrated young rats and castrated aged rats bearing AP grafts than in animals with liver grafts. The in situ molar activity of TH in the ME of castrated young rats was greater than that of castrated or intact aged animals. It is concluded that AP grafts secrete a substance that stimulates DOPA synthesis in the ME of young as well as aged castrated animals, but not in the nigrostriatal system. This stimulation is due to increased catalytic activity of a fixed number of TH molecules rather than an increase in the mass of TH.