Dihydrotestosterone (DHT) Stimulates Progesterone Secretion and Decreases Cortisol Production By H295R Human Adrenocortical Cells

BAQUEDANO MARÍA SONIA; MACEIRAS, MERCEDES; SARACO NORA; ALIBERTI PAULA; ESPERANZA B. BERENSZTEIN; RIVAROLA MARCO A; BELGOROSKY ALICIA

Congreso; Endocrine Society's 97th Annual Meeting (ENDO 2015); 2015

17-Hydroxyprogesterone (17OHP) can be converted to DHT via the backdoor pathway without the intermediacy of DHEA, androstenedione and testosterone (T). Liquid Chromatography?Tandem Mass Spectrometry analysis of urinary steroids showed this pathway is a major route to DHT in pathological states in which 17OHP accumulates, including 21-hydroxylase (21OH) and POR deficiencies. However, the relevance of the backdoor pathway to human adrenal physiology is unknown. We have previously described that the postnatal human adrenal gland expresses androgen receptor and the enzymes to complete all the steps in the backdoor pathway to DHT without a clear age and zone-specific pattern(1). Aim: The aim of the study was to evaluate the role of DHT on human adrenal steroidogenesis. Material and Methods: The effects of DHT upon steroid production in human adrenal NCI-H295R cells were measured by immunoassay. Results: 17OHP incubation (300nM, 24h) of H295R cells caused an increment in DHT/T ratio, showing the integrity of the backdoor pathway in H295R cells. DHT significantly decreased cortisol and stimulated progesterone and aldosterone basal (-1.3, +1.8 and +4 fold, respectively) and 8-bromo-cAMP-induced (-1.6, +2,2 and +2 fold, respectively) production from NCI-H295R cells in a dose-dependent manner at concentrations ≥ 100nM (p