Steroid hormones regulate many crucial physiological processes such as reproduction, response to stress, salt balance and metabolic processes. Any alteration in their production or activity can have major pathophysiological implications. Steroid production occurs in the gonads or adrenals and is regulated by the hypothalamic-pituitary axis. The luteinising hormone (LH) or the adrenocorticotropic hormone (ACTH) bind respectively to their receptor present on the surface of Leydig cells in the testis or adrenal cells, leading to the activation of key enzymes in the steroidogenic pathway. Herein, we want to assess whether the steroidogenic pathway can be activated using photoactivated genes at specific wavelengths, bypassing the necessity of LH or ACTH binding to their receptors.
We employed an in vitro approach and transfected steroidogenic cell lines and adrenal cells (MLTC1: Leydig cells and Y1: Adrenal cells) with control and optogenetic constructs. Cells were exposed to different regimens of light (time and mode: pulsatile versus constant). Our data demonstrates that following transfection of the optogenetic construct, light exposure increases levels of steroids in the media, as measured by mass spectrometry. Transcript levels of key steroidogenic genes, including StAR, were significantly increased following light exposure only in cells transfected with the optogenetic constructs.
These novel findings provide a proof of concept as to the efficiency of optogenetic tools to improve endogenous steroid profiles. This data offers a potential refinement over current therapy approaches with less side effects, treatment burden and better dose management.