Sandhoff T W, McLean M P
Department of Obstetrics and Gynecology, University of South Florida College of Medicine, 4 Columbia Drive, Rm 529, 33606, Tampa, FL.
Endocrine. 1996 Jun;4(3):259-67. doi: 10.1007/BF02738692.
Steroidogenic acute regulatory (StAR) protein is thought to mediate the rapid increase in steroid hormone biosynthesis in response to tropic hormones by facilitating cholesterol transport to the inner mitochondrial membrane where the P450 side-chain cleavage enzyme (P450scc) is located. Since cholesterol delivery is the regulated step in steroidogenesis and is dependent onde novo protein synthesis, StAR mRNA levels were examined in response to the tropic hormones, pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). The results of this investigation revealed that major StAR mRNA transcripts of 3.4 and 1.6 kb and a less abundant transcript of 1.2 kb were detected in the adrenal, ovary, and testis. Within the ovary, StAR mRNA levels were regulated by PMSG and hCG. The two major transcripts were increased in the immature rat ovary following PMSG administration and in the ovary, 8 d after ovulation, in response to stimulation by hCG. Serum progesterone levels were increased following hCG treatment in parallel with the enhanced expression of StAR. Following PMSG treatment, ovarian StAR transcripts at 3.4 and 1.6 kb were each increased twofold. In the ovary, 8 d following ovulation, basal ovarian StAR mRNA levels were elevated up to sixfold relative to the preovulatory StAR mRNA levels. Even with the enhanced basal level of StAR mRNA within the ovary 8 d postovulation, hCG administration still resulted in a 2.5- and 7-fold increase in the 3.4 and 1.6 kb (p<0.025) transcripts, respectively, and a 58% increase in serum progesterone. In contrast to the dramatic alterations in StAR mRNA expression following hormonal stimulation, P450scc mRNA levels remained unchanged in response to hCG stimulation. The levels of serum progesterone paralleled the change in ovarian StAR mRNA in all experiments. This study provides the first evidence that StAR mRNA expression in the rat ovary is mediated by gonadotropins, further supporting its important role in the regulation of steroid hormone biosynthesis.
类固醇生成急性调节（StAR）蛋白被认为通过促进胆固醇转运至线粒体内膜（P450侧链裂解酶（P450scc）所在位置），从而介导甾体激素生物合成在对促性腺激素反应时的快速增加。由于胆固醇转运是类固醇生成中的调节步骤且依赖于从头合成蛋白质，因此检测了StAR mRNA水平对促性腺激素——孕马血清促性腺激素（PMSG）和人绒毛膜促性腺激素（hCG）的反应。本研究结果显示，在肾上腺、卵巢和睾丸中检测到了3.4 kb和1.6 kb的主要StAR mRNA转录本以及一个丰度较低的1.2 kb转录本。在卵巢内，StAR mRNA水平受PMSG和hCG调节。在未成熟大鼠卵巢中，给予PMSG后以及排卵后8天的卵巢中，在hCG刺激下，两种主要转录本均增加。hCG处理后血清孕酮水平升高，与StAR表达增强平行。给予PMSG处理后，卵巢中3.4 kb和1.6 kb的StAR转录本各自增加了两倍。在排卵后8天的卵巢中，基础卵巢StAR mRNA水平相对于排卵前StAR mRNA水平升高了高达六倍。即使在排卵后8天卵巢内StAR mRNA基础水平增强的情况下，给予hCG仍分别导致3.4 kb和1.6 kb转录本增加2.5倍和7倍（p<0.025），血清孕酮增加58%。与激素刺激后StAR mRNA表达的显著变化相反，P450scc mRNA水平在hCG刺激下保持不变。在所有实验中，血清孕酮水平与卵巢StAR mRNA的变化平行。本研究首次提供证据表明，大鼠卵巢中StAR mRNA表达由促性腺激素介导，进一步支持了其在甾体激素生物合成调节中的重要作用。
