Dehidroepiandrosterone modifies GH release from cultured pituitary cells. Mechanism of action

SUÁREZ CECILIA, VELA J, BECÚ-VILLALOBOS D

San Luis

Congreso; XXXV Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2003

SAFE

There has been a strong resurgence of interest in DHEA (the main steroid produced by the adrenal gland) because of its suggested antitumoral and anti-ageing effects. We recently showed that DHEA in vivo was able to increase GH release, and partially reverse ether-induced inhibition of GH. The aim of this study was to determine the effects of DHEA on basal or GHRH- and somatostatin (STT)-induced GH secretion in normal pituitary cells in vitro. Pituitary cells of 60-day old female rats were cultured and stimulated with DHEA in combination with STT or GHRH. Then the GH, cAMP and [Ca++]i increase were measured by RIA or by the Fura-2 fluorometric method. DHEA (1*10-3 to 10-7M) did not modify basal GH secretion, but it increased GH secretion induced by GHRH (10-8M) (227±20 and 321±15% of basal secretion for GHRH and DHEA+GHRH, respectively). This effect was paralleled by cAMP production in response to GHRH. But it was not related to the intracellular Ca++ movilization induced by GHRH, wich was in fact reduced by DHEA pretreatment. On the other hand, DHEA partially reversed STT (10-8M)- induced GH inhibition (45±6 vs 74±8% of basal secretion for STT and DHEA+STT, respectively) without affecting STT-induced decrease in cAMP production. We concluye that GH release evoked by DHEA in vivo may be related to its direct pituitary modulation of GHRH and STT action.