Effects of tibolone and conventional HRT on the expression of estrogen and progesterone receptors in the breast.
OBJECTIVE
There is evidence that long-term hormone replacement therapy (HRT) is associated with an increased breast cancer risk. The aim of this study was to assess the effects of tibolone on estrogen and progesterone receptors in comparison to the effects of conventional HRT in the breast of surgically postmenopausal macaques.


METHODS
Sixty macaques were bilaterally ovariectomized 3 months before hormonal treatment was initiated. The animals were randomized into four treatment groups, including tibolone (TIB), conjugated equine estrogens (CEE), conjugated equine estrogens+medroxyprogesterone acetate (CEE+MPA) and control animals (C). After 2 years treatment, breast tissues were collected, fixed and paraffin embedded. Immunohistochemistry assays with monoclonal antibodies for estrogen receptors (ERalpha and ERbeta) and progesterone receptors (PRA and PRB) were performed.


RESULTS
The expression of ERalpha was markedly decreased in the CEE+MPA group as compared to C and TIB groups. The TIB group was not different from the C and CEE groups. No significant differences were found for ERbeta immunostaining. The expression of PRA was strongly increased in the TIB group as compared to the C and CEE+MPA groups. Immunostaining of PRB was increased in the CEE and TIB treated animals as compared to both C and CEE+MPA groups.


CONCLUSIONS
Tibolone increased the expression of both PRA and PRB, without affecting ERalpha and ERbeta expression in the macaque breast. These findings indicate that the effects of tibolone in breast tissue could be mediated via differential regulation of PRA and PRB isoforms and therefore distinct from those observed with conventional HRT.
Ma
L
L
Division for Reproductive Endocrinology, Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
Hofling
M
M
Masironi
B
B
von Schoultz
B
B
Cline
J M
JM
Sahlin
L
L
D000818:Animals; D001940:Breast / Q000187:drug effects*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000378:metabolism; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D005260:Female; D020249:Hormone Replacement Therapy; D008137:Longitudinal Studies; D008252:Macaca fascicularis; D008525:Medroxyprogesterone / Q000494:pharmacology; D009652:Norpregnenes / Q000494:pharmacology*; D010052:Ovariectomy; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; C027385:tibolone; D008525:Medroxyprogesterone