Effects of bromocriptine on pituitary organelle marker enzyme activities in lactating and postlactating rats: selective activation of lysosomal prolactin proteolytic activity.
Effects of the dopamine agonist 2-bromo-alpha-ergocryptine (bromocriptine) on plasma and pituitary PRL and enzyme activities in lactating and postlactating rats have been investigated. Lactating rats which had been suckling their young for 3 days were given a single sc injection of bromocriptine or solvent. The treated and control animals were divided into 2 further groups. One group (lactating rats) was permitted to suckle their pups for a further 12 or 24 h; the young were removed from the other group (postlactating rats). Homogenates were prepared from the anterior pituitaries and assayed for organelle marker enzyme activities. When 0.5-500 micrograms bromocriptine were administered to lactating rats for 24 h, pituitary PRL was increased by all doses, but only the 500-micrograms dose significantly reduced plasma PRL. Total protein was unchanged, lysosomal acid PRL proteolytic activity increased 8-fold, N-acetyl-beta-glucosaminidase and beta-glucuronidase (lysosomes) were unchanged, acid phosphatase (lysosomes and endoplasmic reticulum) was increased by three of four doses, 5'-nucleotidase and alkaline phosphatase (plasma membrane) were increased 4-fold, neutral-alpha-glucosidase (endoplasmic reticulum) and malate dehydrogenase (mitochondria) were unchanged, and catalase (peroxisomes) was significantly increased. Bromocriptine (500 micrograms) administration to lactating and postlactating rats for 12 and 24 h significantly decreased the pituitary DNA but not the total protein content of the pituitaries in all animals. The lysosomal acid PRL proteolytic activity and the lysosomal enzyme activities, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were increased by suckling withdrawal alone. Acid PRL proteolytic activity was further increased (to 18-fold) by coadministration of bromocriptine, whereas the increase in the activities of the other lysosomal marker enzymes was blocked. Malate dehydrogenase activity (mitochondria) was also increased by litter removal and blocked by bromocriptine. The activity of the plasma membrane markers 5'-nucleotidase and alkaline phosphatase were increased by litter removal, and bromocriptine further increased both enzyme activities. The activity of neutral-alpha-glucosidase (endoplasmic reticulum) was unchanged by any treatment. The results demonstrate that bromocriptine produces significant changes in the activities of lysosomal marker enzymes, particularly acid PRL proteolytic activity, as well as marker enzymes of plasma membranes and other organelles in pituitaries of lactating and postlactating rats.
D015720:5'-Nucleotidase; D000118:Acetylglucosaminidase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D007774:Lactation; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000378:metabolism; D009708:Nucleotidases / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000648:ultrastructure*; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D000520:alpha-Glucosidases / Q000378:metabolism
D001971:Bromocriptine; D011388:Prolactin; D008291:Malate Dehydrogenase; D002374:Catalase; D009708:Nucleotidases; D000469:Alkaline Phosphatase; D015720:5'-Nucleotidase; D000520:alpha-Glucosidases; D005966:Glucuronidase; D000118:Acetylglucosaminidase