Liver and Steroid Hormones—Can a Touch of p53 Make a Difference?

Abstract

The liver is the main metabolic organ in the body, serving as a significant hormonal secretory gland and functioning to maintain hormone balance and homeostasis. Steroid hormones regulate various biological pathways, mainly in the reproductive system and in many metabolic processes. The liver, as well as steroid hormones, contribute significantly, through functional intertwine, to homeostasis maintenance, and proper responses during stress. Malfunction of either has a significant impact on the other and may lead to severe liver diseases as well as to several endocrine syndromes. Thus, the regulation on liver functions as on steroid hormones levels and activities is well-controlled. p53, the well-known tumor suppressor gene, was recently found to regulate metabolism and general homeostasis processes, particularly within the liver. Moreover, p53 was shown to be involved in steroid hormones regulation. In this review, we discuss the bi-directional regulation of the liver and the steroid hormones pointing to p53 as a novel regulator in this axis. A comprehensive understanding of the molecular mechanisms of this axis may help to prevent and treat related disease, especially with the increasing exposure of the population to environmental steroid hormones and steroid hormone-based medication.

Gain-of-Function Mutant p53: All the Roads Lead to Tumorigenesis

“…The tumor-suppressor activity of p53 is mainly attributed to its transcriptional regulation of genes that are involved in numerous cellular processes, such as cell cycle arrest, apoptosis, senescence, DNA repair, and differentiation [1,2]. Moreover, accumulating data points to p53 involvement in numerous biological processes, such as forming a barrier to stem cell formation [3,4], metabolism [5,6], regeneration [7], prevention of liver pathologies [8,9], interaction with viruses [10], endocrinology circuits [11] and serving as the guardian of tissue hierarchy [12].…”

Metabonomic Profile of Macrosteatotic Allografts for Orthotopic Liver Transplantation in Patients With Initial Poor Function: Mechanistic Investigation and Prognostic Prediction

“…As derivatives of cholesterol, steroids were mainly regulated by liver. Steroid derangement might cause NAFLD and inflammation in liver ( Charninatan et al, 2019 ). Concensus on benefits from early withdraw of steroid after LT also implied its potential toxicity for post-transplant prognosis ( Lerut et al, 2009 ; Kimura et al, 2018 ).…”

Diet Composition Affects Liver and Mammary Tissue Transcriptome in Primiparous Holstein Dairy Cows

“…Steroid hormones including mineralocorticoids, glucocorticoids, androgens, estrogens, and progestogens [32,33] are involved in regulation of various biological pathways associated with the reproductive system and maintenance of the entire-body metabolic homeostasis [34]. The liver plays a crucial role in steroid hormones and general cholesterol metabolism, including biosynthesis of cholesterol [34,35].…”

“…Steroid hormones including mineralocorticoids, glucocorticoids, androgens, estrogens, and progestogens [32,33] are involved in regulation of various biological pathways associated with the reproductive system and maintenance of the entire-body metabolic homeostasis [34]. The liver plays a crucial role in steroid hormones and general cholesterol metabolism, including biosynthesis of cholesterol [34,35]. The study of Shi et al (2018) indicated that cholesterol synthesis in liver was quadratically increased with increasing dietary forage levels from 20% to 80%, with a peak detected Taken together, the bioinformatic analyses of the DEG affected by CS vs. MF in both liver and mammary tissue reveal an effect on few signaling pathways related to adipokines and neurons.…”