Centre for Clinical and Basic Research, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana, 81-00163 Rome, Italy.
Endocrinology. 2011 Jan;152(1):113-25. doi: 10.1210/en.2010-0674. Epub 2010 Nov 17.
The mineralocorticoid receptor (MR) mediates aldosterone- and glucocorticoid-induced adipocyte differentiation. Drospirenone (DRSP) is a potent synthetic antimineralocorticoid with progestogenic and antiandrogenic properties, which is widely used for contraception and hormone replacement therapy. We investigated its potential role on adipocyte differentiation. The effects of DRSP were studied in murine preadipocyte cell lines and primary cultures of human preadipocytes. Differentiation markers and mechanisms underlying phenotypic variations in response to DRSP were explored. Early exposure to DRSP during differentiation led to a marked dose-dependent inhibition of adipose differentiation and triglyceride accumulation in 3T3-L1 and 3T3-F442A cells. DRSP also markedly inhibited adipose conversion of human primary preadipocytes derived from visceral (mesenteric and epicardial) and subcutaneous fat. This effect was MR-dependent and did not involve the glucocorticoid, androgen, or progesterone receptors. DRSP inhibited clonal expansion of preadipocytes and decreased expression of PPARγ, a key transcriptional mediator of adipogenesis, but had no effect on lipolysis, glucose uptake, and PPARγ binding to its ligands. DRSP exerts a potent antiadipogenic effect that is related to an alteration of the transcriptional control of adipogenesis via an antagonistic effect on the MR. Selective MR blockade therefore has promise as a novel therapeutic option for the control of excessive adipose tissue deposition and its related metabolic complications.
盐皮质激素受体（MR）介导醛固酮和糖皮质激素诱导的脂肪细胞分化。屈螺酮（DRSP）是一种具有孕激素和抗雄激素特性的强效合成抗盐皮质激素，广泛用于避孕和激素替代治疗。我们研究了它在脂肪细胞分化中的潜在作用。在鼠前体脂肪细胞系和人前体脂肪细胞的原代培养中研究了 DRSP 的作用。探讨了 DRSP 对表型变化的影响及其作用机制。分化过程中早期暴露于 DRSP 会导致 3T3-L1 和 3T3-F442A 细胞中脂肪分化和甘油三酯积累的显著剂量依赖性抑制。DRSP 还明显抑制了来自内脏（肠系膜和心外膜）和皮下脂肪的人原代前体脂肪细胞的脂肪转化。这种作用依赖于 MR，不涉及糖皮质激素、雄激素或孕激素受体。DRSP 抑制前体脂肪细胞的克隆扩张，并降低脂肪生成的关键转录调节剂 PPARγ 的表达，但对脂肪分解、葡萄糖摄取和 PPARγ 与其配体的结合没有影响。DRSP 发挥出强烈的抗脂肪生成作用，这与通过对 MR 的拮抗作用改变脂肪生成的转录控制有关。因此，选择性 MR 阻断有望成为控制过度脂肪组织沉积及其相关代谢并发症的新治疗选择。
