Full oestrogenic activity of C19-delta 5 adrenal steroids in rat pituitary lactotrophs and somatotrophs

Abstract

Oestrogens are known to exert specific stimulatory effects on basal and dopamine (DA)-inhibited prolactin (PRL) release as well as on PRL cell content in rat adenohypophysial cells in primary culture. Recently, we have demonstrated that classical oestrogens increase growth hormone (GH) release and cellular GH content in rat pituitary somatotrophs. Since there is evidence that 5-androstene-3 beta, 17 beta-diol (delta 5-diol), a metabolite of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) can induce typical oestrogenic responses in target tissues, we have investigated the effect of C19 adrenal steroids and compared them to that of 17 beta-oestradiol (E2) on the above-indicated parameters. Following a 72-h incubation, maximal concentrations of E2, delta 5-diol and DHEA caused a similar increase in PRL cell content at respective EC50 values of 0.020, 14 and 115 nM. The sensitivity of lactotrophs to DA action was decreased by approximately 4-fold after a 48-h exposure to maximal concentrations of delta 5-diol or DHEA. The time course of the antidopaminergic effect of delta 5-diol and DHEA was almost superimposable to that of E2. A 72-h incubation with 5 microM DHEA-S, a concentration within the range of blood levels found in women, doubled (P less than or equal to 0.001) cellular PRL accumulation. On the other hand, androstenedione (delta 4-dione) was without effect on any of the parameters measured. All stimulatory effects induced by maximal effective concentrations of delta 5-diol, DHEA or DHEA-S were competitively inhibited by simultaneous incubation with the antioestrogen LY156758. The amplitude of the stimulatory effects of delta 5-diol and DHEA on GH cell content as well as on spontaneous GH-releasing factor (GRF)-induced GH release was superimposable to that observed with E2. The effect of the steroids on GH cell content was exerted at 0.016 nM (E2), 12 nM (delta 5-diol) and 250 nM (DHEA). Simultaneous incubation with LY156758 completely blocked the effect of maximally effective concentrations of E2, delta 5-diol and DHEA in somatotrophs. Furthermore, a physiological concentration of DHEA-S (5 microM) enhanced spontaneous as well as GRF-induced GH release. On the other hand, delta 4-dione as well as testosterone and dihydrotestosterone did not alter GH release. The present data demonstrate that delta 5-diol, DHEA and DHEA-S can exert full oestrogenic effects in lactotrophs and somatotrophs, thus supporting their potential oestrogenic role under both physiological and pathological conditions.