COMPARISON OF THE ACTIONS OF RU 38486 AND MEGESTROL-ACETATE IN THE MODEL OF A TRANSPLANTABLE ADRENOCORTICOTROPIN-SECRETING AND PROLACTIN-SECRETING RAT PITUITARY-TUMOR
- 1 January 1985
- journal article
- research article
- Vol. 45 (3) , 1015-1019
Abstract
The effects of the progesterone antagonist RU 38486 [17-.beta.-hydroxy-11-.beta.-(4-dimethylaminophenyl)-17-.alpha.-(1-propynyl)estra-4,9-dien-3-one] and the progesterone agonist megestrol acetate on the growth of the estrogen-progesterone receptor-positive transplantable ACTH/prolactin-secreting rat pituitary tumor 7315a were examined. RU 38486 (2.5 mg/kg per day) for 30 days significantly inhibited tumor size, tumor weight and the plasma prolactin and ACTH concentrations, while the same dose of megestrol acetate only inhibited pituitary tumor weight. Megestrol acetate inhibited both the release and total ACTH content of the anterior pituitary gland, while RU 38486 increased both the release and the total ACTH content. Studies with ACTH secretion by cultured normal rat pituitary cells showed that megestrol acetate (1 .mu.M) did not affect corticotropin-releasing factor (CRF)-stimulated ACTH release after 4-h exposure, but inhibited CRF-stimulated ACTH release by 50% after 24-h preincubation. The glucocorticoid-like effect of 1 .mu.M megestrol acetate in this model was similar to that exerted by 10 nM dexamethasone. Acute exposure or preincubation of rat pituitary cells with RU 38486 (1 .mu.M) did not influence CRF-stimulated ACTH release, while preincubation for 24 h revealed a dose-dependent reversing effect of RU 38486 on dexamethasone-induced inhibition of CRF-stimulated ACTH release. In this model, 1 .mu.M RU 38486 completely overcame the effect of 10 .mu.M dexamethasone. Megestrol acetate and RU 38486 have inhibitory effects on the growth of the 7315a tumor. They differ both with regard to their effects on the progesterone and the glucocorticoid receptor, with megestrol acetate exerting an agonistic and RU 38486 an antagonistic action.This publication has 8 references indexed in Scilit:
- Treatment of metastatic breast cancer patients with different dosages of megestrol acetate; dose relations, metabolic and endocrine effectsEuropean Journal of Cancer and Clinical Oncology, 1984
- Induction of menstruation by an antiprogesterone steroid (RU 486) in primates: site of action, dose-response relationships, and hormonal effectsFertility and Sterility, 1983
- Basal and dopamine-inhibited prolactin secretion by rat anterior pituitary cells: Effects of culture conditionsMolecular and Cellular Endocrinology, 1983
- Effects of megestrol acetate on growth and secretion of a pituitary tumorEuropean Journal of Cancer and Clinical Oncology, 1981
- Effects of a Luteinizing Hormone-Releasing Hormone Analog and Tamoxifen on the Growth of an Estrogen-Induced Prolactin-Secreting Rat Pituitary Tumor and Its Influence on Pituitary Gonadotropins*Endocrinology, 1981
- Progestin therapy in advanced breast cancer: Megestrol acetate—an evaluation of 160 treated casesCancer, 1980
- The Inability of Bromocriptine to Inhibit Prolactin Secretion by Transplantable Rat Pituitary Tumors: Observations on the Mechanism and Dynamics of the Autofeedback Regulation of Prolactin Secretion*Endocrinology, 1979
- EFFECTS OF MEGESTROL ON OESTRADIOL INDUCED GROWTH OF THE PROSTATIC LOBES AND THE SEMINAL VESICLES IN CASTRATED RATSActa Endocrinologica, 1976