Effects of norethisterone acetate and tamoxifen on serum prolactin levels, uterine growth and on the presence of uterine immunoreactive prolactin in estradiol-treated ovariectomized rats.
The aim of the present work was to study the effects of the antiestrogen tamoxifen (TAM), of progestin norethisterone acetate (NA) and of their combination on serum prolactin levels, uterine growth and the presence of uterine immunoreactive prolactin in estradiol-treated rats. Ovariectomized female Wistar rats were injected sc with estradiol valerate (VE, 50 micrograms/rat per week) or oil vehicle. During the second week, estradiol-treated rats also received NA (0.12 or 1.0 mg/rat, sc, daily) or TAM (0.06 mg/rat) alone or in combination with NA (0.12 mg). Serum prolactin levels were suppressed to the same extent in the TAM- and 1.0 mg NA-treated groups compared with rats given estrogen alone (2.3 +/- 0.3 and 5.6 +/- 1.5 ng/ml for TAM and NA groups vs 39.7 +/- 3.6 ng/ml for VE groups, P < 0.05). Except for the lowest dose of NA, uterine wet weight and DNA content were significantly reduced in all groups compared to estradiol alone (236.8 +/- 18.0 and 295.6 +/- 27.8 mg vs 309.4 +/- 32.2 mg for uterine weight in TAM and NA groups vs VE, respectively, P < 0.05; and 1.14 +/- 0.05 and 0.93 +/- 0.04 mg/uterus vs 1.33 +/- 0.06 mg/uterus for uterine DNA in TAM and NA groups vs VE groups). The combination of NA and TAM resulted in a higher degree of suppression of uterine growth than when each drug was used alone, indicating an additive antiproliferative effect of NA and TAM. Although no prolactin immunostaining was detected in the uterus of rats treated with estradiol, uterine immunoreactive prolactin was identified in those treated with NA, TAM or both.(ABSTRACT TRUNCATED AT 250 WORDS)
Spritzer
P M
PM
Departamento de Fisologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
Barbosa-Coutinho
L M
LM
Poy
M
M
Orsi
V
V
Dahlem
N
N
Silva
I S
IS
D000818:Animals; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D010052:Ovariectomy; D011388:Prolactin / Q000097:blood* / Q000187:drug effects / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology
D013629:Tamoxifen; D004958:Estradiol; D011388:Prolactin; D000077563:Norethindrone Acetate; D009640:Norethindrone