PARENT SESSION
Gonadal Steroids

EFFECT OF ESTRADIOL ON THE EARLY STEP OF STEROIDOGENIC PATHWAY IN ZONA GLOMERULOSA CELLS OF OVARIECTOMIZED RATS.

Kau, Mei-Mei¹, Kan, Shu-Fen², Chang, Ling-Ling³, Wang, Paulus², ^{1 2 3}

ABSTRACT- Our previous study found that the activities of aldosterone synthase and 11-hydroxylase in zona glomerulosa (ZG) cells are increased by administration of estradiol. However, the effects of estradiol on the early step of aldosterone steroidogenic pathway in ZG cells are unclear. The present study is to investigate the effects of estradiol on the activity of cytochrome P450 side-chain cleavage enzyme (P450scc) and the expression of steroidogenic acute regulatory protein (StAR) in ZG cells. Ovariectomized (Ovx) rats were subcutaneously injected with sesame oil or estradiol benzoate (EB, 12.5, 25, or 50 g/kg) once daily for 3 days. After decapitation, the adrenal glands from oil- and EB-treated Ovx rats were prepared to ZG cells. The ZG cells were incubated with or without 25-hydroxy-cholesterol (a membrane-permeable cholesterol, substrate of P450scc) in the presence or absence of trilostane (an inhibitor of 3-hydroxysteroid dehydrogenase) at 37 C for 1 h. The levels of aldosterone, pregnenolone and progesterone in plasma and/or medium were measured by RIA. The protein expression of StAR in ZG cells was analyzed by Western blot. EB increased the level of plasma aldosterone and the basal release of aldosterone and pregnenolone from ZG cells of Ovx rats. In oil- and EB-treated groups, incubation of ZG cells with trilostane decreased progesterone production and increased pregnenolone accumulation. In the presence of trilostane, the conversion of 25-hydroxy-cholesterol to pregnenolone in EB (50 g/kg)-treated group was greater than that in oil-treated group. EB (50 g/kg)-treated group had a higher expression of StAR in ZG cells as compared with oil-treated group. These results suggested that the increases of the P450scc activity and the StAR protein expression in ZG cells were involved in the stimulatory effect of estradiol on aldosterone steroidogenesis.

KEY WORDS: estradiol, aldosterone, P450scc, StAR protein