Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.
 ...
PMID:Estriol add-back therapy in the long-acting gonadotropin-releasing hormone agonist treatment of uterine leiomyomata. 1068 31

Estriol has been showed to prevent bone loss in osteoporotic rats and postmenopausal women, but the mechanisms remain unclear. In the present study, we evaluated the effect of estriol on osteoblastic MG-63 cells in vitro, and compared its action with 17beta-estradiol (E2). Cell proliferation was determined by measuring total cell numbers and [3H]thymidine incorporation. Cell function was studied by measuring alkaline phosphatase (ALP) activity and secreted osteocalcin. Our data showed that estriol stimulated MG-63 cells proliferation in a dose-dependent manner, but had no influence on ALP activity in MG-63 cells and osteocalcin production. Compared with estriol treatment, E2 showed a stronger proliferation. Estrogen receptor (ER) alpha and beta expression in MG-63 cells can be detected by Western immunoblot analysis, and the proliferative response to E2 and estriol can be all abrogated by ER antagonist ICI 182,780. In conclusion, estriol stimulates osteoblastic MG-63 cells proliferation, but has no effects on differentiation. The proliferative response to estriol is mediated by the ER. These results suggest that estriol has an effect on osteoblastic proliferation, and this may contribute to its actions on prevention of bone loss.
 ...
PMID:Effects of estriol on the proliferation and differentiation of human osteoblastic MG-63 cells. 1453 35