Direct transcriptional targets of sex steroid hormones in bone

Area of Science:

• Endocrinology and Bone Biology
• Molecular Endocrinology
• Genetics and Genomics

Background:

• Sex steroid hormones, androgens and estrogens, play a vital role in regulating bone mineral density (BMD) in mammals.
• The precise molecular mechanisms by which these hormones act directly on bone cells remain incompletely understood.
• Nuclear receptors (NRs) mediate the effects of androgens and estrogens, but their direct targets in osteoblasts and osteoclasts are largely unknown.

Purpose of the Study:

• To review and synthesize current knowledge on the direct gene targets of androgen and estrogen receptors in bone cells.
• To discuss models of hormone and receptor deficiency in mouse and human bone to understand in vivo phenotypes.
• To compare experimental evidence of gene regulation by NRs in osteoblasts and osteoclasts with observed in vivo effects.

Main Methods:

• Review of existing literature on hormone and receptor deficiency models in bone.
• Focus on studies identifying direct gene targets regulated by androgen receptor (AR) and estrogen receptor (ER) binding to DNA enhancers or promoters.
• Synthesis and comparison of experimental data on AR and ER target genes in osteoblasts and osteoclasts with in vivo observations.

Main Results:

• Discussion of various mouse and human bone models lacking specific hormones or their receptors.
• Identification and summary of genes directly regulated by AR and ER in osteoblasts and osteoclasts.
• Comparison of direct gene regulation data with the overall effects of androgens and estrogens on bone in living organisms.

Conclusions:

• Understanding direct NR targets in bone cells is critical for elucidating hormone action on bone mineral density.
• This review consolidates evidence on AR and ER direct gene regulation in osteoblasts and osteoclasts.
• Further research comparing direct targets with in vivo phenotypes will refine our understanding of steroid hormone effects on bone.