Biochemical parameters in the anterior pituitary during the course of tumorigenesis induced by diethylstilbestrol treatment.
Treatment of F344 rats with diethylstilbestrol (DES) for 1-2 months induces a prolactin (PRL)-secreting pituitary adenoma. After 8 weeks of DES treatment, we have shown that the ratio of regulatory subunits of the cAMP-dependent protein kinase (RI/RII) increased in the tumors. Presently we report the variations in RI/RII ratio, pituitary weight, DNA content, serum PRL, nuclear estrogen receptor (E2R) and of ornithine decarboxylase (ODC) activity from the time of DES pellet implantation until 8 weeks. Pituitary weight, DNA content and serum PRL rose significantly at 4 weeks with a maximum at 6-8 weeks, and significantly correlated with each other. E2R and ODC activity increased from week 1 onwards, with a maximum at 2 weeks and decreased at 8 weeks. Both variables showed a positive correlation but neither E2R nor ODC activity correlated with pituitary weight, DNA or serum PRL. Values for RI remained stable with time, but RII decreased progressively. The RI/RII ratio was maintained around unity between 1-4 weeks, increasing to 1.6-2 thereafter. This ratio positively correlated with pituitary weight and DNA. It is suggested that during tumor induction by estrogen in a sensitive strain of rats, growth signals with different time-courses become activated. Increases in pituitary weight and DNA content, indicators of mammotroph hypertrophy and hyperplasia, were preceded by early rises in E2R and ODC activity. Increases in the RI/RII ratio accompanied the adenomatous change, suggesting their role in cell transformation after 6 weeks of estrogen exposure.
Piroli
G
G
Laboratorio de Bioquimica Neuroendócrina, Instituto de Biología y Medicina Experimental-CONICET, Buenos Aires, Argentina.
Lima
A E
AE
Díaz-Torga
G
G
De Nicola
A F
AF
D000236:Adenoma / Q000139:chemically induced* / Q000378:metabolism*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D004054:Diethylstilbestrol / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000139:chemically induced* / Q000378:metabolism*; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011959:Receptors, Estradiol / Q000378:metabolism; D013997:Time Factors
D004273:DNA, Neoplasm; D011959:Receptors, Estradiol; D004054:Diethylstilbestrol; D011388:Prolactin; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases; D009955:Ornithine Decarboxylase