Androgen receptor and progesterone receptor (AR/PR)

The androgen receptor (AR) and progesterone receptor (PR) are distinct members of the 3-ketosteroid receptor subfamily within the nuclear receptor superfamily (UniProt: P10275, P06401). AR is primarily responsible for mediating the effects of androgens like testosterone, which are crucial for male sexual differentiation and the maintenance of secondary male characteristics (PubMed: 25213483). PR mediates the physiological effects of progesterone, playing a central role in the female reproductive system, particularly in the uterus and mammary glands during the menstrual cycle and pregnancy (PubMed: 26361158). Both receptors function as ligand-dependent transcription factors that, upon activation, bind to specific DNA sequences to regulate the expression of genes involved in cell growth, survival, and differentiation. In oncology, AR is a primary target for treating prostate cancer, while PR status is a critical biomarker and therapeutic target in breast cancer and gynecological disorders. Pharmacological intervention includes agonists for hormone replacement and antagonists or selective modulators for treating hormone-dependent malignancies and reproductive conditions. Because this entry combines two separate proteins with unique genetic loci and biological profiles, it represents a functional grouping rather than a single molecular target.

Other names

NR3C4NR3C3Dihydrotestosterone receptorPGRNuclear receptor subfamily 3 group C member 4Nuclear receptor subfamily 3 group C member 3

These receptors function as ligand-activated transcription factors. Upon binding their respective steroid hormones (androgens or progestogens), the receptors undergo conformational changes, dissociate from chaperone proteins like HSP90, dimerize, and translocate into the nucleus. In the nucleus, they bind to specific DNA sequences known as hormone response elements (HREs) located in the promoter or enhancer regions of target genes. This binding recruits various co-activators or co-repressors and the RNA polymerase II machinery to modulate the transcription of genes involved in growth, differentiation, and metabolic processes (PubMed: 25213483, 26361158).