Skeletal and gene-regulatory functions of nuclear sex steroid hormone receptors.

The wide variety of sex hormone actions underlie bone growth and health, and their actions mediate gene regulation by the cognate nuclear receptors. Nuclear androgen and estrogen receptors (AR, and ERα/ERβ) are hormone-dependent and DNA binding- transcription regulatory factors, and gene regulation by sex hormones often accompany with chromatin remodeling under aid of a number of co-regulators. As sex hormone biosynthesis is under highly regulated systemic and local regulations, the skeletal actions of sex hormones could be inferred from only the phenotypic abnormalities in skeleton in mouse genetic models deficient of nuclear receptors selectively in specific types of bone cells as well as at specific cell differentiation stages. Anabolic androgen actions and anti-bone resorptive estrogen actions are discussed here from the phenotypic abnormalities in such model mice. Though rapid gene regulation by sex hormones may not require chromatin reorganization, dynamic chromatin reconfiguration looks to facilitate profound and long-term hormonal actions. In this review, we focus the recent findings in gene regulation at a chromatin level, particularly of the function of enhancer RNAs transcribed from strong enhancers, and in the role of liquid-liquid phase separation state in transcription initiation through chromatin reconfiguration.