A possible role for lysosomes in the inhibitory action of dopamine on prolactin release

The effect of dopamine on lysosomal function in the anterior pituitary gland and on PRL secretion was investigated in vivo and in vitro. When anterior pituitary glands were examined by electron microscopy, it was found that PRL cells in pituitary tissue from rats that had been treated for 8 h with the dopamine precursor, L-dihydroxyphenylalanine (L-dopa), contained more multivesicular bodies (i.e. lysosomes) than did PRL cells in pituitary tissue from vehicle-treated animals. In addition, a large number of the lysosomes in PRL cells of L-dopa-treated rats appeared to have undergone fusion with PRL secretory granules (i.e. crinophagy). When anterior pituitary glands were homogenized and fractionated by continuous sucrose density gradient centrifugation, it was found that most of the activity of the lysosomal enzyme, β-glucuronidase, was present in gradient fractions containing subcellular particles, viz. lysosomes, that had an approximate density of 1.2. Treatment of rats with Ldopa resulted in an increase in the β-glucuronidase activity associated with these particles. On the other hand, treatment of rats with haloperidol, a dopamine antagonist, or with α-methyltyrosine, an inhibitor of dopamine synthesis, resulted in a decrease in lysosomal enzyme activity in the anterior pituitary gland. Incubation of pituitary tissue with dopamine resulted in an increase in β-glucuronidase activity in the tissue. This increased activity was detectable after 15 min of exposure of the tissue to dopamine and was dose-related between 10^-9-10^-5 M dopamine. Moreover, the dose-response curves for the stimulatory effect of dopamine on β-glucuronidase activity and for the inhibitory effect of dopamine on the release of PRL were superimposable. Preincubation of pituitary tissue with the dopamine antagonist cis-flupenthixol, an agent known to bind to dopamine receptors, resulted in an attenuation of the stimulatory effect of dopamine on β-glucuronidase activity and the inhibitory effect of dopamine on PRL release. In addition, preincubation of anterior pituitary tissue with chloroquine or NH4CI, agents that are known to interfere with lysosomal function, also resulted in an attenuation of the stimulatory effect of dopamine on β-glucuronidase activity as well as the inhibitory effect of dopamine on PRL release. It is suggested that the dopamine-induced stimulation of lysosomal enzyme activity is part of the mechanism by which dopamine inhibits the release of PRL.