Effects of tibolone on estrogen biosynthesis in the mammary tissue of postmenopausal monkeys.
OBJECTIVE
To evaluate the long-term effects of tibolone on estrone sulfate (E1S)-sulfatase activity in breast tissue in a primate model (Macaca fascicularis) in comparison with conventional hormone therapies.


METHODS
Ovariectomized female animals (n = 112) were randomized into five groups and treated for 2 years. Treatment included tibolone at 0.05 mg/kg (LoTib, n = 23) or 0.2 mg/kg (HiTib, n = 23), conjugated equine estrogens at 0.042 mg/kg (CEE, n = 24), CEE + medroxyprogesterone acetate at 0.167 mg/kg (CEE+MPA, n = 21), or placebo (controls, n = 21). E1S-sulfatase activity was evaluated by incubating homogenized breast tissue with [H]-E1S. Thin-layer chromatography was performed to separate the products estrone (E1) and estradiol (E2). Histomorphometry was performed to measure the amount of epithelial and fat tissue in the mammary gland.


RESULTS
Significantly more E2 than E1 was produced in all groups. E1S-sulfatase activity did not differ among the groups. E1S-sulfatase activity was highest in HiTib animals with less fatty breasts (5.9 fmol total estrogen/mg of protein/min; P < or =0.05) and lowest in HiTib animals with more fatty breasts (2.8 fmol total estrogen/mg of protein/min; P = 0.004 relative to less fatty breasts).


CONCLUSIONS
We conclude that tibolone had a differential effect on local estrogen biosynthesis in animals with high and low breast fat content. Therefore, breast tissue composition affects the steroidogenic response to hormonal treatment.
Stute
Petra
P
Department of Obstetrics and Gynecology, University of Münster, Münster, Germany.
Register
Thomas C
TC
Blair
Robert M
RM
Cline
J Mark
JM
D000818:Animals; D002855:Chromatography, Thin Layer; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004967:Estrogens / Q000096:biosynthesis*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000502:physiology; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D023421:Models, Animal; D009652:Norpregnenes / Q000494:pharmacology*; D010052:Ovariectomy; D017698:Postmenopause; D011897:Random Allocation; D043266:Steryl-Sulfatase / Q000378:metabolism
D020847:Estrogen Receptor Modulators; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D017258:Medroxyprogesterone Acetate; D043266:Steryl-Sulfatase; C027385:tibolone