Communication between genomic and non-genomic signaling events coordinate steroid hormone actions

Abstract

Steroid hormones are lipophilic molecules produced in one cell that can travel great distances within the body to elicit biological effects in another cell. In the canonical pathway, steroid hormone binding to a nuclear receptor (NR), often in the cytoplasm, causes the receptor to undergo a conformational change and translocate to the nucleus, where it interacts with specific sequences of DNA to regulate transcription. In addition to the classical genomic mechanism of action, alternate mechanisms of steroid activity have emerged that involve rapid, non-genomic signaling. The distinction between these two major mechanisms of action lies in the subcellular location of the initiating steroid hormone action. Importantly, the mechanisms of action are not exclusive, in that each can affect the activity of the other. Here, we describe the different types of genomic and non-genomic steroid hormone signaling mechanisms and how they can influence one another to ultimately regulate biology. Further, we discuss the approaches being used to study the non-genomic signaling events and address important caveats to be considered when designing new experiments. Thus, this minireview can serve as an introduction to the diverse signaling mechanisms of steroid hormones and offers initial, experimental guidance to those entering the field.

Androgens, oestrogens and endometrium: a fine balance between perfection and pathology

“…A recent review provided a useful summary of the wide range of different non-genomic signalling pathways and how the different genomic and non-genomic pathways may interact (Wilkenfeld et al 2018).…”

Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

“…Transcriptional control of gene expression may take from some hours to a number of days. Examples of these types of receptors are the estrogen receptors alpha and beta (ERa and Erb), the androgen receptor (AR), and the vitamin D receptor (VDR) (Wilkenfeld et al, 2018). Along with the transcriptional pathway, SH induce rapid, non-transcriptional effects, including blood vessels dilation or tracheal relaxation.…”

“…Here, the complex binds to hormone-response elements to either induce or repress the transcription of genes encoding for ion channels. Upon transcription, ion channel mRNA is translated into the corresponding protein and the ion channel is transported to the cell membrane (Bohra and Bhateja, 2015;Wilkenfeld et al, 2018). (B) Non-transcriptional pathways primarily involve the binding of the SH to a GPCR triggering second messenger pathways which may activate proteins targeting to ion channels.…”

Rapid effects of 17β-estradiol on aggressive behavior in songbirds: Environmental and genetic influences

“…In general, effects of steroids seen within 30 min of administration are likely mediated by non-genomic mechanisms (Cornil et al, 2006). However, given that non-genomic signaling can potentiate genomic signaling (and vice versa) (Wilkenfeld et al, 2017), we will hereafter refer to these as “rapid” effects of E 2 . Research on avian model systems has been at the forefront of our understanding of the ethological relevance of these non-classical mechanisms of steroid action.…”

“…The mERs also rapidly affect kinases such as extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase, and protein kinases A and C (Heimovics et al, 2012; Mermelstein and Micevych, 2008; Micevych and Dominguez, 2009; Micevych and Mermelstein, 2008; Moss and Gu, 1999). Importantly, in some contexts, the non-genomic effects of E 2 potentiate subsequent genomic effects of E 2 (Vasudevan and Pfaff, 2008; Wilkenfeld et al, 2017). While rapid effects of E 2 have become widely accepted within the past 20 years, much of this work has been done in vitro with dissociated neurons, brain slices, or cell lines.…”