Effects of long-term tibolone treatment on nuclear sex steroid hormone receptors and G-protein-coupled estrogen receptor-1 expression in the macaque uterus.
OBJECTIVE
Tibolone is an alternative hormone treatment for managing climacteric symptoms in postmenopausal women. The aim of this study was to determine the effects of long-term tibolone (TIB) treatment in comparison with conventional hormone therapy on the expression and distribution of estrogen receptor (ER) α, ER-β, G-protein-coupled ER-1 (GPER), progesterone receptor (PR) A, PRB, androgen receptor (AR), and syndecan-1 in the macaque uterus.


METHODS
Eighty-eight cynomolgus macaques (Macaca fascicularis) were ovariectomized and treated orally with TIB, a combination of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA), CEE alone, or vehicle for 2 years. Immunohistochemistry was used to evaluate the protein expression and distribution of the receptors in the monkey uterus.


RESULTS
In the TIB group, immunostaining of ER-α and GPER was higher in the luminal and glandular epithelium, respectively, as compared with the CEE + MPA group. PRA and PRB protein expression was increased in the stroma and myometrium of the TIB group as compared with the controls. AR immunoreactivity was also up-regulated by TIB treatment in the stroma as compared with no treatment. Furthermore, epithelial immunoreactivity of AR was higher after TIB treatment as compared with CEE + MPA treatment.


CONCLUSIONS
TIB treatment influences the protein expression of sex hormone receptors in monkey endometrium differently from that observed after conventional hormone therapy. We suggest that the observed differences in AR expression by TIB as compared with combined treatment may be of importance for endometrial atrophy as well as for the beneficial bleeding profile associated with this treatment.
Division for Reproductive Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Mariana
M
Hulchiy
Hua
H
Zhang
J Mark
JM
Cline
Angelica Lindén
AL
Hirschberg
Lena
L
Sahlin
D000818:Animals; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use; D005260:Female; D020249:Hormone Replacement Therapy; D008251:Macaca; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D009652:Norpregnenes / Q000627:therapeutic use*; D010052:Ovariectomy; D011987:Receptors, Steroid / Q000032:analysis / Q000378:metabolism*; D053668:Syndecan-1 / Q000032:analysis; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D020847:Estrogen Receptor Modulators; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D011987:Receptors, Steroid; D053668:Syndecan-1; D017258:Medroxyprogesterone Acetate; C027385:tibolone