Title: Genetics and Bioenergetics of Mitochondria Influencing the Etiology and Pharmacology of Steroidal Hormones
Volume: 2
Issue: 4
Author(s): Deodutta Roy, Jai Parkash and Satya Narayan
Affiliation:
Keywords:
steroid hormones, defects in genetics and physiology of mitochondria, human diseases
Abstract: Mitochondria are important targets of steroid hormone action. The receptors for steroid hormones, including estrogen, thyroxine and glucocorticoid, are present in the mitochondria, while steroid hormone responsive elements are also found in the mitochondrial genome. The presence of the steroid hormone receptors in the mitochondria, transport of ligands to the mitochondria, sequences of hormone response elements in the mitochondrial genome, and modulation of mitochondrial encoded genes by steroid hormones support a direct action of steroid hormones on mitochondrial gene transcription. This is parallel to the primary actions of the steroid hormones on nuclear gene transcription as a mechanism to coordinate regulation of mitochondrial biogenesis by steroid hormones. The cross-talk between the cell nucleus and the mitochondria appears to control steroid hormone-induced signaling involved in the apoptosis, proliferation, and differentiation of both normal and malignant cells. Evaluation of the defects in genetics and physiology of mitochondria, specifically in steroids hormone-related endocrine diseases in humans, sugge sts that several variants of human endocrine diseases, including cancer, manifest as a result of mitochondrial physiologic and metabolic compensation of genetic defects. The steroidal agents control biogenesis and maintenance of mitochondria through the crosstalk between nuclear and mitochondrial genomes. The regulation of mitochondrial transcription by steroidal hormones, presumably occurring through pathways similar to those that take place in the nucleus, opens a new way to better understand steroid hormone and vitamin action at the cellular level. Therefore, an in-depth analysis of such regulatory mechanisms is pertinent to the development of novel drugs and gene therapy strategies for the treatment of steroid hormone-dependent diseases related to mitochondrial disorders including cancer.
