Steroid hormones regulate many crucial physiological processes including reproduction, response to stress, salt balance and various metabolic processes. Any alteration in their production or activity can have major pathophysiological implications such as cancers, endocrine disorders (ie polycystic ovary syndrome, Addison disease, hypogonadism, diabetes, stress) [1]. Hormone replacement therapy is the main treatment for steroid hormone deficiency, yet it involves daily administration and is associated with various short and long term risks. Thus, there is a recognised need to develop safer and more effective therapies to support steroid hormone production to maintain lifelong health. New technologies such as nano-implants inserted under the skin are being developed and could allow the assessment and controlled release of steroid with a single injection.
Steroid production (steroidogenesis) in the gonads/adrenals is regulated by the hypothalamic-pituitary axis. The Luteinising hormone (LH) and the adrenocorticotropic hormone (ACTH) bind respectively to their receptor (LHCGR) on the surface of Leydig cells and (MC2R) in adrenal cells. This activates the adenylate cyclase/cAMP production and regulate key enzymes in the steroidogenic pathway [2]. In this project, we developed a new way to control steroidogenic cell function using light-based system [3-4] bypassing the necessity of LH or ACTH binding to their receptors. We used a cell culture system to provide proof of concept that these optogenetic tools can efficiently activate LH and ACTH pathways, and induce endogenous steroid production. Our preliminary data in MLTC1 cells demonstrate that, following transfection of optogenetic construct, light (~470nm) exposure significantly stimulates steroid production. These novel findings provide the basis of a new technology that could be harnessed to develop new therapeutic strategies to control of steroid production, with the potential to transform the management of pathologies associated with steroid deficiency, with the likely benefits (reduced (i) side-effects, (ii) treatment burden and fine-tuned dosing regimens).