Comparative effects of prolactin versus ACTH, estradiol, progesterone, testosterone, and dihydrotestosterone on cortisol release and proliferation of the adrenocortical carcinoma cell line H295R

In this study, using the H295R cell line as a model system, we investigated the role of prolactin (PRL) and steroid hormones in the growth regulation and cortisol release of adrenocortical cells. H295R cells were treated with increasing doses (10⁻¹³–10⁻⁶ M) of PRL, adrenocorticotropic hormone (ACTH), 17β-estradiol (E₂), progesterone (P₄), testosterone (T), and dihydrotestosterone (DHT). As expected, ACTH raised cortisol secretion and increased the proliferation rate of cultured cells. Incubation with T, DHT, E₂, and P₄ for 24 h did not significantly increase cortisol release. Conversely, PRL concentrations of 10⁻⁸–10⁻⁶ M caused a significant increase in the release of cortisol. Long-term (5 days) stimulation of H295R cells with E₂, P₄, and PRL was a trigger to increased cell proliferation, while T and DHT did not alter H295R cell proliferation. Taken together, these results indicate that steroid hormones exert differential effects on adrenocortical function. Additionally, the present study demonstrates that PRL had biphasic actions in regulating adrenocortical function. PRL may form a novel regulatory system for steroid hormone secretion and cell proliferation in the adrenal cortex.