The Role of FKBP5 in Mood Disorders: Action of FKBP5 on Steroid Hormone Receptors Leads to Questions About its Evolutionary Importance

Preclinical and/or clinical evidence has indicated a potential role of steroid hormone-mediated signaling pathways in the development of various neoplastic diseases, while precise mechanisms for the functions of specific receptors remain poorly understood. Specifically, in urothelial cancer where sex-related differences particularly in its incidence are noted, activation of sex hormone receptors, such as androgen receptor and estrogen receptor-β, has been associated with the induction of tumor development. More recently, glucocorticoid receptor has been implied to function as a suppressor of urothelial tumorigenesis. This article summarizes and discusses available data suggesting that steroid hormone receptors, including androgen receptor, estrogen receptor-α, estrogen receptor-β, glucocorticoid receptor, progesterone receptor and vitamin D receptor, as well as their related signals, contribute to modulating urothelial tumorigenesis.

Download Full-text

A conserved mechanism of sirtuin signalling through steroid hormone receptors

Bioscience Reports ◽

10.1042/bsr20193535 ◽

2019 ◽

Vol 39 (12) ◽

Cited By ~ 3

Author(s):

Henry K. Bayele

Keyword(s):

Drug Targets ◽

Metabolic Regulation ◽

Hormone Receptors ◽

Steroid Receptors ◽

Steroid Hormone ◽

Steroid Hormone Receptors ◽

Nuclear Receptor Coregulators ◽

Dafachronic Acid ◽

Important Drug

Abstract SIRT1 and orthologous sirtuins regulate a universal mechanism of ageing and thus determine lifespan across taxa; however, the precise mechanism remains vexingly polemical. They also protect against many metabolic and ageing-related diseases by dynamically integrating several processes including autophagy, proteostasis, calorie restriction, circadian rhythmicity and metabolism. These sirtuins are therefore important drug targets particularly because they also transduce allosteric signals from sirtuin-activating compounds such as resveratrol into increased healthspan in evolutionarily diverse organisms. While many of these functions are apparently regulated by deacetylation, that mechanism may not be all-encompassing. Since gonadal signals have been shown to regulate ageing/lifespan in worms and flies, the present study hypothesized that these sirtuins may act as intermediary factors for steroid hormone signal transduction. Accordingly, SIRT1 and its orthologues, Sir2 and Sir-2.1, are shown to be veritable nuclear receptor coregulators that classically coactivate the oestrogen receptor in the absence of ligand; coactivation was further increased by 17β-oestradiol. Remarkably in response to the worm steroid hormone dafachronic acid, SIRT1 reciprocally coactivates DAF-12, the steroid receptor that regulates nematode lifespan. These results suggest that steroid hormones may co-opt and modulate a phyletically conserved mechanism of sirtuin signalling through steroid receptors. Hence, it is interesting to speculate that certain sirtuin functions including prolongevity and metabolic regulation may be mechanistically linked to this endocrine signalling pathway; this may also have implications for understanding the determinative role of gonadal steroids such as oestradiol in human ageing. At its simplest, this report shows evidence for a hitherto unknown deacetylation-independent mechanism of sirtuin signalling.

Download Full-text

Role of Steroid Hormone Receptors in Development and Puberty

The Receptors ◽

10.1016/b978-0-12-185202-3.50016-0 ◽

1985 ◽

pp. 341-366

Author(s):

B.D. GREENSTEIN ◽

I.M. ADCOCK

Keyword(s):

Hormone Receptors ◽

Steroid Hormone ◽

Steroid Hormone Receptors

Download Full-text

Steroid hormone receptors and prostate cancer: role of structural dynamics in therapeutic targeting

Asian Journal of Andrology ◽

10.4103/1008-682x.183380 ◽

2016 ◽

Vol 18 (5) ◽

pp. 682 ◽

Cited By ~ 11

Author(s):

Raj Kumar

Keyword(s):

Prostate Cancer ◽

Structural Dynamics ◽

Hormone Receptors ◽

Steroid Hormone ◽

Steroid Hormone Receptors ◽

Therapeutic Targeting

Download Full-text

Regulation of progesterone receptor signaling by BRCA1 in mammary cancer

Nuclear Receptor Signaling ◽

10.1621/nrs.04006 ◽

2006 ◽

Vol 4 (1) ◽

pp. nrs.04006 ◽

Cited By ~ 14

Author(s):

Pragati Katiyar ◽

Yongxian Ma ◽

Saijun Fan ◽

Richard G. Pestell ◽

Priscilla A. Furth ◽

...

Keyword(s):

Hormone Receptors ◽

Steroid Hormone ◽

Brca1 Gene ◽

Cell Cycle Checkpoints ◽

Steroid Hormone Receptors ◽

Dna Damage Signaling ◽

Increased Risk ◽

Tumor Types ◽

Inherited Mutations

Inherited mutations of the BRCA1 gene (chromosome 17q21), a tumor suppressor, lead to an increased risk of breast cancer, ovarian cancer, and several other hormone-responsive tumor types. Over the last ten years, BRCA1 has been found to play major roles in DNA damage signaling, repair, and cell cycle checkpoints. In addition, unfolding evidence suggests that BRCA1 functions as a co-regulator for steroid hormone receptors and modulates steroid hormone action. In this paper, we will briefly review this evidence and present a model to address the role of the progesterone and estrogen receptors in BRCA1 mutant mammary carcinogenesis. Finally, we will consider some of the clinical implications of this model.

Download Full-text