Convergence of Multiple Mechanisms of Steroid Hormone Action

Abstract

Steroid hormones modulate a wide array of physiological processes including development, metabolism, and reproduction in various species. It is generally believed that these biological effects are predominantly mediated by their binding to specific intracellular receptors resulting in conformational change, dimerization, and recruitment of coregulators for transcription-dependent genomic actions (classical mechanism). In addition, to their cognate ligands, intracellular steroid receptors can also be activated in a “ligand-independent” manner by other factors including neurotransmitters. Recent studies indicate that rapid, nonclassical steroid effects involve extranuclear steroid receptors located at the membrane, which interact with cytoplasmic kinase signaling molecules and G-proteins. The current review deals with various mechanisms that function together in an integrated manner to promote hormone-dependent actions on the central and sympathetic nervous systems.

Marginal activity of progesterone receptor B (PR-B) in dogs but high incidence of mammary cancer

“…This was true for all three receptor variants. Our findings contrast with the reported ligand-independent effects of the PR in breast cancer cells [33] or brain tissue [34]. This may, however, be due to the fact that those ligand-independent effects are in general fast [35] and may need activation by EGF [36] or neurotransmitters [34], and cannot be found in our experimental setup.…”

Protein kinase C modulates transcriptional activation by the juvenile hormone receptor methoprene-tolerant

“…However, a vast body of work indicates that cellular responses to steroids may be mediated by a small population of classical steroid receptors located at the plasma membrane, which interact with G proteins, signaling kinases and other G protein-coupled receptors, to mediate rapid effects of the hormones (androgen, estrogen, progesterone, etc.) (Mani et al, 2012). The nongenomic steroid activity typically involves the rapid activation of second messenger systems and activation of PKC, PI3K and mitogen-activated protein kinase (Hammes and Levin, 2007; Pietras and Szego, 1975; Szego and Davis, 1967).…”

Storing maternal memories: Hypothesizing an interaction of experience and estrogen on sensory cortical plasticity to learn infant cues

“…Genomic actions are initiated when receptors in turn bind to classical estrogen response elements on DNA sequences resulting in synthesis of transcription factors that trigger the activation or inhibition of intracellular signaling cascades (McEwen and Alves, 1999; Luine and Frankfurt, 2012). A faster mechanism of estrogen action is mediated via an interaction with extranuclear estrogen receptors at the cell surface that then recruit G-protein coupled receptors and signaling kinases, enabling rapid effects of these hormones (Mani et al, 2012). Either or both these mechanisms of estrogen action could be relevant for hormonal priming of neurons within the auditory cortex during parturition, which would potentially allow neurons to be more receptive and malleable in response to pup calls.…”