In vivo effect of cabergoline, a dopamine agonist, on estrogen-induced rat pituitary tumors.
Cabergoline (CG) is a dopamine agonist that inhibits the secretion of prolactin (PRL) and growth hormone. In the present study, we evaluated the in vivo effect of CG on PRL secretion and the pituitary tumor induced by estrogen. Estrogen was administered by subcutaneous injection to 4-week-old Fischer 344 rats weekly for 10 weeks to induce tumors. On the last day of estrogen administration, doses of either CG or bromocriptine (BC), 0.6 mg/kg, were administered as a single oral route or chronically, given every third day. Sera and pituitary tumors were sampled on each treatment schedule. Serum levels of PRL were measured and the pituitary glands were weighed. Immunohistological evaluation was performed by optical and electron microscopy. A single dose of CG significantly inhibited the serum levels of PRL for 6 days. Following a single dose of BC, the PRL level was significantly inhibited only at 6 hours' postadministration. The continued oral administration of CG significantly reduced both the serum PRL level and the weight of the pituitary during 15 to 60 days of treatment as compared with BC. Morphologic studies revealed that CG reduced the size of the cells and of the granules, and increased the number of granules per unit area of the cytoplasm. These findings suggest that CG inhibits the maturation of PRL secretory granules and the secretion of PRL more than its synthesis. Thus, CG induced a prolonged lowering of PRL and had a good antitumor effect on rat pituitary tumors induced by estrogen.
Eguchi
K
K
Department of Neurosurgery, School of Medicine, Hiroshima University, Japan.
Kawamoto
K
K
Uozumi
T
T
Ito
A
A
Arita
K
K
Kurisu
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001971:Bromocriptine / Q000008:administration & dosage; D000077465:Cabergoline; D003594:Cytoplasmic Granules / Q000648:ultrastructure; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D004873:Ergolines / Q000008:administration & dosage / Q000627:therapeutic use*; D004958:Estradiol; D005260:Female; D008854:Microscopy, Electron; D009929:Organ Size; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D018491:Dopamine Agonists; D004873:Ergolines; D001971:Bromocriptine; D004958:Estradiol; D011388:Prolactin; D000077465:Cabergoline