Table 2.

Adapted from the review Non-genomic actions of sex steroid hormones by Simoncini and Genazzani (105).

Criteria for non-genomic steroid actions	Examples
Very Rapid	Non-genomic steroid signaling occurs within seconds to minutes. Example: In MDA-MB-453 cells treatment with DHT results in induction of p-ERK within 10 min (94).
Does not require RNA/Protein synthesis mediated by steroid receptor	The effects precede and do not require receptor nuclear translocation and RNA or protein synthesis. Example: Effects are seen where canonical gene transcription does not occur (106) and with inhibitors of RNA and protein synthesis such as with the use of Actinomycin D or alpha amanitin (107).
May be induced by membrane bound proteins	Steroids do not have to cross the cell membrane to induce effects Example: If steroids are conjugated to large molecules such as BSA they cannot cross the cell membrane but still bring about effects (108, 109).
Presence of classical steroid receptor is not required	Effects are observed in cells that do not possess classical steroid nuclear receptors Rapid and transient increases in [Ca2+]i have been reported in cells absent of AR expression (110).
Occurs in cells with little or no transcription or translation mechanisms	Can occur in cells with highly compacted chromatin, in which RNA and protein synthesis mechanisms are absent Example: Steroid responses have been detected in sperm cells in which transcription does not occur and platelets which are anucleate (111).
Mutations in the DNA binding domain	Steroids can induce effects even if their classical nuclear receptor has a mutation inhibiting it DNA binding or initiating gene transcription Example: in vivo mouse experiments demonstrated androgen induced rapid phosphorylation of ERK1/2 in presence of mutant AR lacking the 2nd zinc finger of the DBD (112).
Cooperation between genomic and non- genomic actions	Studies have shown non genomic actions of nuclear receptors can act in concert or can directly influence genomic nuclear receptor actions or may occur sequentially. Example: The feedback loop between AR expression and Phosphorylation of ERK1/2 (94).