Adrenocorticotropin hormone regulates sphingosine-1-phosphate synthesis via cortisol in bovine adrenocortical cells.

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) stimulate the synthesis of sphingosine-1 phosphate (S1P) in Gs-coupled receptors dependent manner, enabling S1P to mediate specific bioactivities of FSH and LH. Because adrenocorticotropic hormone (ACTH) also acts via a Gs-coupled receptor to regulate adrenal cortex function, we hypothesized that ACTH could induce S1P secretion in adrenocortical cells, which could then mediate the steroidogenic and number of viable cells effects associated with ACTH. Primary bovine adrenocortical cell cultures were treated with ACTH, and number of viable cells, as well as S1P and cortisol concentrations in the culture media were measured. The effects of exogenous cortisol on number of viable cells, S1P and phosphorylated SPHK1 concentrations were also determined. Results show that the addition of 0.001 μM and 0.1 μM ACTH to the culture medium increased the number of viable adrenocortical cells, and the concentration of cortisol in culture media, respectively. However, ACTH addition did not increase S1P concentrations. Interestingly, a negative correlation between S1P and cortisol concentrations in the culture medium was observed. Moreover, while addition of 0.1 ng/mL cortisol increased S1P and phosphorylated SPHK1 concentrations, increasing cortisol from 1 to 10 ng/mL did not affect phosphorylated SPHK1 but reduced S1P concentration. Thus, while our data suggest that ACTH does not promote S1P synthesis; by stimulating cortisol synthesis, ACTH could be involved in regulation of S1P levels in bovine adrenocortical cells.