Regulation of Steroid Hormone Biosynthesis by the Cytoskeleton

Abstract

Steroid hormones are synthesized in response to signaling cascades initiated by the trophic peptide hormones derived from the anterior pituitary. The mechanisms by which these peptide hormones regulate steroid hormone production are multifaceted and include controlling the transcription of steroidogenic genes, regulating cholesterol (substrate) uptake and transport, modulating steroidogenic enzyme activity, and controlling electron availability. Cytoskeletal polymers such as microfilaments and microtubules have also been implicated in regulating steroidogenesis. Of note, steroidogenesis is a multi-step process that occurs in two organelles, the endoplasmic reticulum (ER) and the mitochondrion. However, the precise mechanism by which substrates are delivered back and forth between these two organelles is unknown. In this review we will discuss the role of components of the cytoskeleton in conferring optimal steroidogenic potential. Finally, we present data that identifying a novel mechanism by which sphingosine-1-phosphate induces mitochondrial trafficking to promote steroidogenesis.

Maternal calorie restriction modulates placental mitochondrial biogenesis and bioenergetic efficiency: putative involvement in fetoplacental growth defects in rats

“…Mitochondria are implicated in numerous critical functions for the fetoplacental development, such as ATP production for placental growth and transplacental nutrient transfers, reduction of oxidative stress, control of cell apoptosis, and production of hormones (17,25,31,34). Mitochondrial defects may contribute to modify the placental activity, which may strengthen the effect of maternal undernutrition and thus be involved in the restriction of both fetal and placental growth.…”

60 YEARS OF POMC: Adrenal and extra-adrenal functions of ACTH

“…This latter effect is mediated by the phosphotyrosine phosphatase, SHP-2 (Rocchi et al 2000), itself activated by PKAdependent serine phosphorylation. This last step has been reported to be essential for cAMP-induced corticosterone secretion (Sewer & Li 2008, Cooke et al 2011, Gallo-Payet & Battista 2014). Li and Sewer ( 2010) showed that these cytoskeleton-associated modifications may dictate the nature of the steroid production.…”

“…Moreover, the observations that ACTH and/or cAMP induced morphological changes of adrenal cells from flat and adherent to round and loosely attached prompted many investigators to investigate how the cytoskeleton (in particular through reorganization of the actin filament network and its associated proteins) was implicated in ACTH responses (Feuillolley & Vaudry 1996, Côté et al 1997, Hall & Almahbobi 1997, Sewer & Li 2008. Over the years, some of these non-canonical pathways have been well documented.…”

A phosphoproteomics approach to elucidate neuropeptide signal transduction controlling insect metamorphosis

“…Cytoskeletal proteins have also been shown to be important for steroid hormone synthesis as inhibitors of actin microfilaments and microtubules disrupt hormone-induced production of steroids (Sewer and Li, 2008). Disruption of cytoskeletal structures impairs cholesterol delivery to the P450 side chain cleavage enzyme (P450scc) that mediates the initial steroidogenic step in vertebrates.…”