The Effects of Synthetic 19-Norprogestins on Osteoblastic Cell Function Are Mediated by Their Non-Phenolic Reduced Metabolites

The study investigated the effects of synthetic 19-norprogestins, norethisterone (NET) and levonorgestrel (LNG), and their A-ring reduced derivatives on osteoblastic cell function in neonatal rat osteoblasts. It was found that these compounds, particularly their 3β,5α- and 3α,5α-tetrahydro derivatives, significantly promoted osteoblast proliferation and differentiation, mimicking estradiol's effects, while progesterone had no effect. The estrogen-like actions of 19-norprogestins were mediated by their non-phenolic reduced metabolites, as evidenced by the inhibition of these effects by finasteride, a 5α-reductase inhibitor. This suggested potential mechanisms for 19-norprogestins in aiding bone restoration in postmenopausal women, with implications for hormone replacement therapy research.