Pure alpha-subunit-secreting mouse pituitary tumor: inhibition of growth and secretion by combined treatment with thyroxine and bromocriptine.
We have recently documented the spontaneous development of a mouse pituitary tumor line (MGH 101A) secreting only the alpha-subunit of the glycoprotein hormones. Secretion of alpha-subunit by MGH 101A was not inhibited by either physiological or pharmacological levels of thyroid hormones. The present study demonstrates that combined treatment with bromocriptine and pharmacological doses of T4 for 1 month significantly decreased both tumor growth and alpha-subunit secretion of MGH 101A in thyroidectomized host mice. Either treatment alone was ineffective. The fall in plasma alpha-subunit concentrations after the combined treatment was probably due to the inhibition of tumor growth, since the decreases in plasma alpha-subunit levels and tumor weights were quantitatively similar, and there was no significant change in tumor steady state concentrations of alpha-subunit mRNA. In two of three experiments, the combined treatment resulted in a significant fall in tumor total DNA concentrations; this suggests that decreased tumor growth was at least in part due to inhibition of tumor cell replication. To compare the effects of the various treatments on the pure alpha-subunit-producing pituitary tumor with their effects on non-tumorous pituitary, we also measured secretion of TSH and PRL into plasma by the host pituitary. Treatment with T4 alone profoundly suppressed plasma concentrations of TSH and significantly reduced plasma PRL levels compared to levels in the thyroidectomized controls. Surprisingly, both thyroidectomized and euthyroid tumor hosts treated with bromocriptine alone showed no suppression of plasma PRL levels. However, combined treatment with bromocriptine and pharmacological doses of T4 resulted in plasma PRL concentrations significantly lower than those after treatment with T4 alone. Thus, the tumor and nontumorous host pituitaries differed in their responses to T4 alone. However, the two tissues were similar in their responses to bromocriptine alone and to combined treatment with bromocriptine and T4. We conclude that combined treatment with T4 and bromocriptine inhibited the growth and secretion of the pure alpha-subunit-secreting tumor MGH 101A. The data on PRL secretion by the host pituitary suggest that T4 may have acted by enhancing the function of dopamine receptors.
J D
JD
Kieffer
D S
DS
Ross
M A
MA
Shupnik
E C
EC
Ridgway
D000818:Animals; D001971:Bromocriptine / Q000627:therapeutic use*; D004247:DNA / Q000032:analysis; D004359:Drug Therapy, Combination; D015292:Glycoprotein Hormones, alpha Subunit; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010446:Peptide Fragments / Q000378:metabolism*; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011388:Prolactin / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*
D015292:Glycoprotein Hormones, alpha Subunit; D010446:Peptide Fragments; D010908:Pituitary Hormones, Anterior; D001971:Bromocriptine; D011388:Prolactin; D004247:DNA; D013974:Thyroxine