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Effects of 17ß-Estradiol and Medroxyprogesterone Acetate upon MtTW15 Mammosomatotropic Pituitary Tumor Growth and Hormone Production in Male and Female Rats¹

Department of Anatomy, University of Minnesota, Minneapolis, Minnesota 55455

The purpose of this study was to characterize the effects of two functionally diverse steroids, 17ß-estradiol and medroxy-progesterone acetate (MPA), on MtTW15 rat mammosomatotropic pituitary tumor growth and hormone production. Steroid responsiveness, as well as the hormonally autonomous nature of the tumor, was studied by treating both male and female tumor-bearing rats for 7 weeks with weekly injections of either 17ß-estradiol (600 ng/g body weight/week) or MPA (200 µg/g body weight/week) and, subsequently, comparing both the tumor weights and the in vivo production of growth hormone (GH) and prolactin (PRL) among the treatment groups. Large tumors (6 to 20 gm) were obtained in all treatment groups, indicating hormonal autonomy; however, tumors were markedly smaller, on the average, in untreated males and ovariectomized females. Treatment of such rats with 17ß-estradiol stimulated tumor growth. Radioimmunoassay of tumor and serum GH and PRL levels in all treatment groups indicated the following: (a) tumors from untreated male or female hosts did not favor the production of one hormone over the other to any great extent; (b) MPA, however, promoted significant increases (p < 0.05) in GH production in both male and female tumor-bearing rats while having little effect on the production of PRL; and (c) 17ß-estradiol significantly inhibited (p < 0.05) GH production and promoted PRL production by tumors borne by either sex. Selected studies utilizing multiple doses of MPA (1 to 500 µg per gm body weight per week) and 17ß-estradiol (10 to 800 ng per gm body weight per week) were accomplished and demonstrated that hormone production can be influenced in a dose-related manner. These results indicated that the estrogen-induced MtTW15 rat pituitary tumor is hormonally autonomous, yet divergently responsive to two different classes of steroidal compounds, thus making this tumor line an appropriate model for the study of hormonally responsive pituitary tumor cells.

¹ This study was supported in part by the American Cancer Society Institutional Research Grant IN-13-R-25 and NIH Grant AM26962.

² To whom requests for reprints should be addressed.

Received 9/ 4/80. Accepted 2/ 4/81.