Although it has been recently shown that GnRH is capable of increasing plasma PRL levels in humans, the role played by the steroid hormone environment in influencing this response has not been clarified. Fourteen intact and 14 castrated subjects with carcinoma of the prostate were studied before and after daily treatment with 1.5 mg estradiol benzoate (E2B), im, for 9 days PRL responsiveness was tested after GnRH was given as an iv bolus or a continuous infusion for 4 h. During a 4-h saline infusion after E2B treatment, plasma PRL levels were measured in 8 intact and 8 castrated subjects for control purposes. No significant increase in PRL levels was noted after iv bolus or infusion of GnRH in intact or castrated men. After the administration of pharmacological doses of E2B for 9 days, plasma PRL levels increased significantly in all subjects after both the iv bolus and the infusion of GnRH. During saline infusion, a significant decrease in plasma PRL levels was observed in all subjects. Plasma gonadotropin levels showed the expected increase after GnRH administration. Our findings confirm that GnRH is one of the numerous substances capable of stimulating PRL release in humans and demonstrate that in men: 1) pharmacological doses of estrogen induce a PRL response to GnRH, and 2) GnRH elicits different patterns of PRL release depending on the modality of administration. Finally, the physiological role of GnRH in PRL release, if any, remains to be established.
The effect was studied of chronic uridine treatment on the recovery of striatal D-2 dopamine (DA) receptors after their irreversible blockade by N-ethoxycarbonyl-2-ethoxy-I,2-dihydroquinoline (EEDQ) in young (40 days old) and adult (14 months old) male rats using [3H]spiperone as radioligand. Chronic uridine treatment (15 mg kg-1 day-1, i.p., 14 days) causes a reduction of [3H]spiperone binding sites in striatum of young rats. This treatment also produces an increase in the rate of recovery of striatal [3H]spiperone-labelled DA receptors in young, but not in adult rats. Catalepsy and exploratory locomotor activity, two behaviours associated with blockade versus activation of DA receptors, were evaluated in the same rats. The behavioural recovery from the EEDQ-induced syndrome is more rapid in the young rats treated with uridine than in the saline-treated group. The behavioural recovery in old rats was not affected by chronic uridine treatment. Thus, in young rats the pyrimidine nucleoside uridine may modulate the steady state and the turnover rate of striatal D-2 DA receptors.
The monosialoganglioside GM1 displays complex effects on protein phosphorylation of rat cerebral cortex membrane preparations. The exogenous ganglioside at a concentration of 350 microM in absence of calcium only stimulated the phosphorylation of a protein of MW = 64,000. In presence of 1 mM calcium a twofold effect is observed irrespective of the phosphoprotein considered. In particular there is an enhancement of 32P incorporation in four major phosphoproteins of MW = 160,000, 140,000, 64,000 and 50,000 in presence of GM1 compared with that observed with calcium alone. The maximal stimulating effect is achieved with a ganglioside concentration of 35 microM. This effect is inhibited by the addition of 100 microM trifluoperazine (TFP), a phenothiazine known to inhibit calmodulin and protein kinase-C activities. These four proteins represent the major substrates for the calcium/calmodulin-dependent protein kinase with the MW = 64,000 and 50,000 proteins co-migrating with the autophosphorylated subunits of this enzyme. In addition, the ganglioside inhibited the phosphorylation of three proteins with MW = 86,000, 20,000 and 14,000. The electrophoretic properties of these phosphoproteins are similar to the autophosphorylated form of protein kinase-C and to the rat myelin basic proteins, respectively. The effect of the ganglioside on their phosphorylation is not influenced by TFP. Finally, a protein with an apparent molecular weight of 46,000 shows also an increased phosphorylation in presence of GM1. The reported results indicate that exogenous GM1 can have profound effects on different kinases such as the calcium/calmodulin dependent protein kinase, the protein kinase-C and also some unknown calcium-independent protein kinases.
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