ergoline and Hyperplasia

Topics: Adenofibroma; Alkaline Phosphatase; Animals; Antineoplastic Agents; Biopsy, Fine-Needle; Cabergoline; Cats; Diagnosis, Differential; Ergolines; Hyperplasia; Male; Mammary Glands, Animal; Mammary Neoplasms, Animal; Orchiectomy; Phosphorus; Progesterone; Treatment Outcome

Dopamine agonists are known to increase the incidence of Leydig cell hyperplasia/adenomas when administered to rats over periods of 1-2 years. We have examined the early changes in factors affecting Leydig cell growth/hyperplasia after chronic oral administration of one of these dopamine agonists, Mesulergine (CU32-085) [N-(1-6-dimethylergolin-8 alpha-yl)-N,N-dimethylsulphamide hydrochloride), to Sprague-Dawley (SD) rats. Eight-week-old rats were given the dopamine agonist (2 mg/kg body weight/day) in food for 5 or 57 weeks. The dopamine agonist treatment had no significant effect on food intake, body weight, and testis and seminal vesicle size, but significantly decreased testicular interstitial fluid volume at 5 weeks (by 51%). Leydig cells isolated from rats treated with the dopamine agonist for 5 weeks exhibited an increase in the rate of protein synthesis compared with the controls (by 28%). This treatment, however, had no significant effect on the number of Leydig cells or macrophages as assessed by histological examination of testicular sections. Treatment with the dopamine agonist for 57 weeks caused a 36 and 28% increase in the number of Leydig cells and macrophages, respectively. Nodules of Leydig cells, indicating the first signs of tumor development, were present in testes from the 57- but not the 5-week-treated animals or the controls of both groups, although an increase in the number of Leydig cells occurred with aging. Thick-walled arterioles were found in the intertubular spaces of the testis sections from rats treated for 57 weeks. These findings suggest that chronic treatment of male SD rats with the dopamine agonist causes hypertrophy of Leydig cells within 5 weeks (as assessed by [3H]methionine incorporation), followed by hyperplasia within 2 years, prior to the development of Leydig cell adenomas, which occur within 1-2 years after the initiation of treatment.

Topics: Adenoma; Animals; Antiparkinson Agents; Body Weight; Dopamine Agonists; Dose-Response Relationship, Drug; Ergolines; Extracellular Space; Hyperplasia; Leydig Cell Tumor; Leydig Cells; Male; Organ Size; Rats; Rats, Sprague-Dawley; Testicular Neoplasms

Mesulergine (N,N-dimethylsulphamide-N'-1,6-dimethyl-ergoline-8 alpha-yl) is an active semisynthetic ergot derivative with lower antiprolactin potency compared with bromocriptine or pergolide. Since no data are yet available on the effects of mesulergine on pituitary dopamine receptors, the present study has been designated to elucidate the influence of this drug on prolactin secretion in vivo and in vitro and 3H-spiperone binding by the anterior pituitary gland in female Wistar rats with experimentally induced hyperprolactinemia. Three weeks after bilateral ovariectomy and subcutaneous implantation of silastic tubes, containing 10 mg of diethylstilbestrol, a dramatic rise in serum prolactin levels was observed (1.67 +/- 0.23 vs. 80.82 +/- 3.80 ng/ml; P less than 0.001). Mesulergine attenuated the stimulatory effect of diethylstilbestrol on serum prolactin level in a time- and dose-dependent fashion. At concentration range between 10(-5) and 10(-7) M it also inhibited prolactin secretion from cultured rat pituitary cells to the medium during 180 min incubation in a dose-dependent manner. Scatchard analyses performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture, prepared from the pituitaries from rats treated for four weeks with diethylstilbestrol, showed that chronic mesulergine treatment (in dose of 3.0 mg/kg injected s.c. for 10 days) induced a significant decrease in the number of dopamine D2-binding sites (Bmax 28.00 +/- 4.20 vs. 42.80 +/- 4.76 fmol/10(6) cells; P less than 0.01) without any changes in D2-receptor affinity. Our results suggested that antiprolactin activity of mesulergine in vivo and in vitro is probably associated with agonistic effect of this drug on D2-dopamine receptors.

Topics: Animals; Antiparkinson Agents; Bromocriptine; Diethylstilbestrol; Dose-Response Relationship, Drug; Ergolines; Female; Hyperplasia; Hyperprolactinemia; Pergolide; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Wistar; Receptors, Dopamine D2; Spiperone; Time Factors; Tritium

The growth reaction of the rat adenohypophysis to estradiol was previously found to be potentiated by dopaminergic antagonists (perphenazine) and inhibited by thyroid hormones and dopaminergic agonists. In the present experiment a combination of estradiol, lisuride and thyroid hormones was tested. Sixty male Wistar rats were divided into 6 groups: 1. controls; 2. estradiol benozate (E) in aqueous microcrystal suspension 1 mg/rat twice a week; 3. Thyreoidin (SPOFA) 0.2% in the food (T); E + T; 5. E + lisuride (N-D-6-methyl-8-isoergonelyl)-N'N-diethyl carbamide hydrogen maleate, 200 micrograms/rat per day in the food (L); 5. E + T + L. After 3 weeks the adenohypophysial weights, histology (PAS Orange G, indirect immunoperoxidase technique) and electron microscopic morphometry were examined. The increase in adenohypophysial weight was inhibited by T, L and significantly more by the combination T + L. The increased incidence of prolactin cells after estradiol was inhibited by T and L and equally by the combination T + L. The effect of both inhibitory substances (T + L) was also additive on the relative size of the nucleoli of PRL cells: marked nucleolar inhibition similar to that produced by cytostatics was observed in the E + T + L group of animals.

Topics: Adrenal Glands; Animals; Cell Nucleus; Dopamine Agents; Ergolines; Estradiol; Hyperplasia; Lisuride; Male; Microscopy, Electron; Organ Size; Organelles; Pituitary Gland, Anterior; Rats; Rats, Inbred Strains; Testis; Thyroid Hormones

Hyperplastic anterior pituitary glands were produced in female rats by treatment with 10 mg of diethylstilbestrol in Silastic tubing. This led to increased numbers of immunoreactive prolactin cells and increased serum prolactin levels. After 6 weeks of diethylstilbestrol treatment, one group of rats was treated with daily injections of pergolide for 3 weeks. Pergolide produced a significant decrease in pituitary gland weight and in serum prolactin levels but did not change the percentage of prolactin cells significantly, compared with that of control rats. Ultrastructural studies showed a significant increase in the numbers of prolactin secretory granules and numerous large intracellular bodies with associated secretory granules in pituitaries from rats treated with pergolide. In one group of rats in which the diethylstilbestrol was discontinued for 3 weeks after 6 weeks of treatment there was a significant decrease in pituitary gland weight and serum prolactin and a significant decrease in the percentage of prolactin cells, compared with values in the rats treated with diethylstilbestrol for 9 weeks. These results indicate that pergolide causes decreased release of prolactin from secretory granules in anterior pituitary prolactin cells and an increase in the numbers of PRL secretory granules per cell but does not change the percentage of prolactin-producing pituitary cells after 3 weeks of treatment.

Topics: Animals; Diethylstilbestrol; Ergolines; Female; Growth Hormone; Hyperplasia; Microscopy, Electron; Pergolide; Pituitary Gland, Anterior; Prolactin; Rats; Rats, Inbred F344

Three-week administering of Estradiolbenzoate to male rats results in hyperplasia of adenohypophysis with increase of Orange G slightly positive cells and chromophobe cells, loosening of structure giving a trabecular picture, and stressed vascularization. Simultaneous administering of Ergoline compounds (Deprenon, Lisuride) rather limited the transformation. However, the differentiation of single pituitary cells due to Estradiolbenzoate remained substantially uninfluenced.

Topics: Animals; Ergolines; Estradiol; Hyperplasia; Lisuride; Male; Pituitary Gland, Anterior; Rats

The general characteristics of the preneoplastic lesions of the human mammary gland, as they are known through histologic description, are outlined, and data obtained from the experimental analysis of mammary gland preneoplasia in five areas of endeavor are discussed. Results obtained with transplantation procedures and aimed at defining the growth potential of hyperplastic outgrowths are reported. Information derived from the study of events able to induce benign hyperplastic outgrowths or their malignant transformation in the murine mammary gland is summarized. Attempts to predict neoplastic transformation in morphologically hyperplastic epithelium of human and rodent glands are discussed. The present status of efforts toward the prophylaxis of preneoplastic lesions of the mammary gland is described. Considerations of the relationship between preneoplasia and tumor dormancy conclude the presentation.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Breast; Breast Neoplasms; Bromocriptine; Cell Transformation, Neoplastic; Cells, Cultured; Ergolines; Female; Humans; Hyperplasia; Mammary Neoplasms, Experimental; Mammary Tumor Virus, Mouse; Mice; Neoplasm Transplantation; Precancerous Conditions; Transplantation, Heterologous; Urethane

Daily treatment (for 12 to 14 months) of 2-month-old nulliparous or 8-month-old multiparous C3H/HeJ mice with 0.1 mg of 2-bromo-alpha-ergocryptine (CB-154) or 6-methyl-8-beta-ergoline-acetonitrile, efficacious inhibitors of prolactin secretion, markedly reduced the incidence of spontaneous mammary hyperplastic nodules and mammary tumors. CB-154 appeared to be more effective than 6-methyl-8-beta-ergoline-acetonitrile in suppressing the incidence of mammary tumors; the ergot virtually prevented the appearance of mammary tumors in nulliparous mice. Daily treatment of 5-month-old estrogen-treated, ovariectomized-hysterectomized C3H/HeJ mice for 12 months with CB-154 also significantly reduced the incidence of hyperplastic nodules and mammary tumors when compared with ovariectomized-hysterectomized mice treated with steroid alone. Daily treatment of multiparous C3H/HeJ mammary tumor-bearing mice with CB-154 or 6-methyl-8-beta-ergoline-acetonitrile generally failed, however, to promote regression of the mammary tumors. Thus significant prophylaxis of early preneoplastic lesions by drug-induced hormone (prolactin) suppression, resulting in a marked reduction in mammary tumor incidence, has been demonstrated in this study.

Topics: Animals; Bromocriptine; Ergolines; Female; Hyperplasia; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Metergoline; Mice; Mice, Inbred C3H; Parity; Precancerous Conditions; Prolactin

One group of male Syrian hamsters received diethylstilbestrol (DES) over a period of 9 months. All developed widespread and severe renal tumors. Another group of male Syrian hamsters was given DES plus 2-bromo-alpha-ergocryptine methanesulfonate (CB154) over the same period. These hamsters either did not develop renal tumors or had renal tumors that were minimal in severity. DES treatment induced hyperplastic and neoplastic changes in the intermediate lobe of the pituitary glands of treated animals, increased the number of prolactin-secreting cells, and decreased the number of somatotrophin-secreting cells. Adding CB154 significantly inhibited those changes in the pituitary gland. Histopathologic and ultrastructural examinations indicated that the renal tumors were carcinomas originating from proximal convoluted tubules.

Topics: Animals; Body Weight; Bromocriptine; Cell Count; Cricetinae; Diethylstilbestrol; Ergolines; Growth Hormone; Hyperplasia; Kidney Neoplasms; Kidney Tubules, Proximal; Male; Mesylates; Organ Size; Pituitary Gland; Pituitary Neoplasms; Prolactin; Testis