Progesterone is extensively metabolized in osteoblasts: implications for progesterone action on bone

Area of Science:

• Endocrinology
• Bone Biology
• Steroid Metabolism

Background:

• The role of progestogens in bone health remains debated, with conflicting evidence on their anabolic effects.
• Localized enzyme activity in bone may influence progesterone's action and explain study discrepancies.

Purpose of the Study:

• To investigate progesterone metabolism in primary human osteoblasts and MG-63 osteoblastic cells.
• To identify key enzymes involved in progesterone transformation within these bone cells.

Main Methods:

• Incubation of osteoblasts and MG-63 cells with radiolabeled and unlabeled progesterone.
• Analysis of progesterone metabolites using two-dimensional thin-layer chromatography.
• Assessment of enzyme mRNA expression via conventional and real-time PCR.

Main Results:

• Progesterone was extensively metabolized in both cell types, primarily to 20α-dihydroprogesterone and 5α-dihydroprogesterone.
• Enzymes like AKR1C1, 5α-reductase type 1, AKR1C2, 3β-HSD type 1, and 3-hydroxysteroid epimerase were expressed.
• Dexamethasone increased 5α-reductase activity in MG-63 cells, while primary osteoblasts showed no change with dexamethasone or estradiol.

Conclusions:

• Human osteoblasts extensively metabolize progesterone, potentially leading to its inactivation and reduced local receptor response.
• Osteoblasts possess the capability to convert progestogens into metabolites that may exert anabolic effects through estrogen receptors.