Long-term sensitivity of uterus and hypothalamus/pituitary axis to 17beta-estradiol is higher than that of bone in rats.

Abstract

We examined the long-term sensitivity of uterus and bone to low-dose 17beta-estradiol in a 4-month experiment in OVX rats and found that a dose of estradiol that fully protected against uterine atrophy did not protect against bone loss. Our results suggest higher estrogen sensitivity of the uterus compared with bone. Estrogen is essential for the function of reproductive tissues and for the normal acquisition and maintenance of bone mass in females. This study was designed to examine the long-term sensitivity of the uterus and bone to low-dose estrogen. In preliminary experiments, we determined the lowest subcutaneous dose of 17beta-estradiol able to fully protect against uterine atrophy in ovariectomized (OVX) rats. This dose was found to be 1.5 microg/kg, given five times per week. Subsequently, groups of sham-operated (SHAM) or OVX 6-month-old rats (n = 8 each) were subcutaneously injected with vehicle or 1.5 microg/kg 17beta-estradiol five times per week. All animals were killed 4 months after surgery. Serum osteocalcin and urinary deoxypyridinoline were measured as biochemical markers of bone turnover. Bones were analyzed by bone histomorphometry and pQCT. Our study clearly showed that a dose of estradiol that restores physiological estradiol serum levels, fully maintains uterine weight in OVX rats at the SHAM control level, and suppresses serum follicle-stimulating hormone (FSH) by 67% relative to OVX vehicle controls does not provide significant protection against OVX-induced bone loss at different cancellous and cortical bone sites. We conclude that the long-term sensitivity of the uterus and the hypothalamus/pituitary axis to 17beta-estradiol is higher than that of bone in rats.