Saxena Deeksha, Escamilla-Hernandez Rosalba, Little-Ihrig Lynda, Zeleznik Anthony J
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, 830 Scaife Hall, 3500 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
Endocrinology. 2007 Feb;148(2):726-34. doi: 10.1210/en.2006-0108. Epub 2006 Nov 9.
Granulosa cells express the closely related orphan nuclear receptors steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1). To determine whether SF-1 and LRH-1 have differential effects on steroid production, we compared the effects of overexpressing LRH-1 and SF-1 on estrogen and progesterone production by undifferentiated rat granulosa cells. Adenovirus mediated overexpression of LRH-1 or SF-1 had qualitatively similar effects. Neither LRH-1 nor SF-1 alone stimulated estrogen or progesterone production, but when combined with FSH and testosterone, each significantly augmented progesterone production and mRNAs for cholesterol side-chain cleavage enzyme and 3beta-hydroxysteroid dehydrogenase above that observed with FSH alone, with SF-1 being more effective than LRH-1. LRH-1 did not augment FSH-stimulated estrogen production, whereas SF-1 produced only a slight ( approximately 30%) augmentation of FSH-stimulated estrogen production. The stimulatory actions of both were reduced by overexpression of dosage-sensitive sex reversal, adrenal hypoplasia congenita, critical region on the X chromosome, gene 1. Expression of either LRH-1 or SF-1 together with constitutively active protein kinase B in the absence of FSH stimulated progesterone production and mRNAs for 3beta-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage enzyme but did not stimulate estrogen production or mRNA for aromatase. These findings demonstrate that LRH-1 and SF-1 have qualitatively similar actions on FSH-stimulated estrogen and progesterone production, which would suggest that these factors may have overlapping actions in the regulation of steroidogenesis that accompanies granulosa cell differentiation.
颗粒细胞表达密切相关的孤儿核受体类固醇生成因子-1（SF-1）和肝脏受体同源物-1（LRH-1）。为了确定SF-1和LRH-1对类固醇生成是否有不同影响，我们比较了过表达LRH-1和SF-1对未分化大鼠颗粒细胞雌激素和孕酮生成的影响。腺病毒介导的LRH-1或SF-1过表达具有定性相似的作用。单独的LRH-1和SF-1均未刺激雌激素或孕酮生成，但与促卵泡激素（FSH）和睾酮联合使用时，二者均显著增加了孕酮生成以及胆固醇侧链裂解酶和3β-羟基类固醇脱氢酶的mRNA水平，且高于单独使用FSH时观察到的水平，其中SF-1比LRH-1更有效。LRH-1未增加FSH刺激的雌激素生成，而SF-1仅使FSH刺激的雌激素生成略有增加（约30%）。剂量敏感性性反转、先天性肾上腺发育不全、X染色体关键区域基因1的过表达降低了二者的刺激作用。在无FSH的情况下，LRH-1或SF-1与组成型活性蛋白激酶B一起表达可刺激孕酮生成以及3β-羟基类固醇脱氢酶和胆固醇侧链裂解酶的mRNA水平，但不刺激雌激素生成或芳香化酶的mRNA水平。这些发现表明，LRH-1和SF-1对FSH刺激的雌激素和孕酮生成具有定性相似的作用，这表明这些因子在伴随颗粒细胞分化的类固醇生成调节中可能具有重叠作用。
