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Department of Biological Chemistry (T.R.-F., R.T., J.O.), The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel; Department of Cell Biology and Biochemistry (S.R.K., D.M.S.), Texas Tech University Health Sciences Center, Lubbock, Texas 79430; and Department of Physiology (K.H.H., D.B.H.), University of Illinois at Chicago, Chicago, Illinois 60612-7342
Address all correspondence and requests for reprints to: Dr. Joseph Orly, Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. E-mail: orly{at}vms.huji.ac.il
The steroidogenic acute regulatory protein (StAR) is a vital mitochondrial protein that is indispensable for the synthesis of steroid hormones in the steroidogenic cells of the adrenal cortex and the gonads. Recent studies have shown that StAR enhances the conversion of the substrate for all steroid hormones, cholesterol, into pregnenolone, probably by facilitating cholesterol entry into the inner compartment of the mitochondria where the steroidogenic cytochrome P450scc complex resides. To study the potential of StAR to affect ovarian steroidogenesis during follicular development, we examined the time-dependent expression of StAR protein and messenger RNA in PMSG/human CG (hCG)-treated immature rats. Western blot analyses and immunohistochemical and RT-PCR methodologies have revealed a biphasic expression of StAR in the ovaries responding to hormones. The first peak of StAR expression was generated by PMSG administration and lasted for 24 h. Furthermore, it was restricted to the entire network of the ovarian secondary interstitial tissue, as well as to a fewer scattered theca-interna cells. The second burst of StAR expression was observed in response to the LH surge, as simulated by hCG. This time, StAR was expressed in the entire theca-interna and interstitial tissue, as well as in those granulosa cells that were confined to periovulatory follicles. Immunoelectron microscopy studies revealed the over 90% of StAR antigenic sites are localized in the inner compartments of the mitochondrion, suggesting a rapid removal of StAR precursor from the mitochondrial surface, where it is believed to exert its activity. Altogether, our observations portray dynamic acute alterations of StAR expression during the process of follicular maturation in this animal model. Furthermore, if StAR indeed determines steroidogenic capacities in the ovary, our findings imply that, in immature rats undergoing hormonally induced first ovulation: 1) the early phases of follicular development are supported by androgen production originating from nonfollicular cells; 2) estrogen production in the granulosa cells of Graafian follicles is nourished by a submaximal androgenic output in the theca-interstitial compartments of the ovary.
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T.-J. Huang and P. Shirley Li Dexamethasone Inhibits Luteinizing Hormone-Induced Synthesis of Steroidogenic Acute Regulatory Protein in Cultured Rat Preovulatory Follicles Biol Reprod, January 1, 2001; 64(1): 163 - 170. [Abstract] [Full Text]
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D. Boerboom and J. Sirois Equine P450 Cholesterol Side-Chain Cleavage and 3{beta}-Hydroxysteroid Dehydrogenase/{{Delta}}5-{{Delta}}4 Isomerase: Molecular Cloning and Regulation of Their Messenger Ribonucleic Acids in Equine Follicles During the Ovulatory Process Biol Reprod, January 1, 2001; 64(1): 206 - 215. [Abstract] [Full Text]
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E. V. Solovyeva, M. Hayashi, K. Margi, C. Barkats, C. Klein, A. Amsterdam, A. J.W. Hsueh, and A. Tsafriri Growth Differentiation Factor-9 Stimulates Rat Theca-Interstitial Cell Androgen Biosynthesis Biol Reprod, October 1, 2000; 63(4): 1214 - 1218. [Abstract] [Full Text]
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 C.L. Chaffin, G.A. Dissen, and R.L. Stouffer Hormonal regulation of steroidogenic enzyme expression in granulosa cells during the peri-ovulatory interval in monkeys Mol. Hum. Reprod., January 1, 2000; 6(1): 11 - 18. [Abstract] [Full Text] [PDF]
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J.-G. Lehoux, D. B. Hales, A. Fleury, N. Brière, D. Martel, and L. Ducharme The in Vivo Effects of Adrenocorticotropin and Sodium Restriction on the Formation of Different Species of Steroidogenic Acute Regulatory Protein in Rat Adrenal Endocrinology, November 1, 1999; 140(11): 5154 - 5164. [Abstract] [Full Text]
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J. Arensburg, A. H. Payne, and J. Orly Expression of Steroidogenic Genes in Maternal and Extraembryonic Cells During Early Pregnancy in Mice Endocrinology, November 1, 1999; 140(11): 5220 - 5232. [Abstract] [Full Text]
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 L. K. Christenson, P. F. Johnson, J. M. McAllister, and J. F. Strauss III CCAAT/Enhancer-binding Proteins Regulate Expression of the Human Steroidogenic Acute Regulatory Protein (StAR) Gene J. Biol. Chem., September 10, 1999; 274(37): 26591 - 26598. [Abstract] [Full Text] [PDF]
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E. Silverman, S. Eimerl, and J. Orly CCAAT Enhancer-binding Protein beta and GATA-4 Binding Regions within the Promoter of the Steroidogenic Acute Regulatory Protein (StAR) Gene Are Required for Transcription in Rat Ovarian Cells J. Biol. Chem., June 18, 1999; 274(25): 17987 - 17996. [Abstract] [Full Text] [PDF]
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 W. E. Thompson, J. Powell, K. H. Thomas, and J. A. Whittaker Immunolocalization and Expression of the Steroidogenic Acute Regulatory Protein During the Transitional Stages of Rat Follicular Differentiation J. Histochem. Cytochem., June 1, 1999; 47(6): 769 - 776. [Abstract] [Full Text]
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S. Gräs, J. Hannibal, and J. Fahrenkrug Pituitary Adenylate Cyclase-Activating Polypeptide Is an Auto/Paracrine Stimulator of Acute Progesterone Accumulation and Subsequent Luteinization in Cultured Periovulatory Granulosa/Lutein Cells Endocrinology, May 1, 1999; 140(5): 2199 - 2205. [Abstract] [Full Text]
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 C. L. Chaffin, D. L. Hess, and R. L. Stouffer Dynamics of periovulatory steroidogenesis in the rhesus monkey follicle after ovarian stimulation Hum. Reprod., March 1, 1999; 14(3): 642 - 649. [Abstract] [Full Text] [PDF]
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A. Kerban, D. Boerboom, and J. Sirois Human Chorionic Gonadotropin Induces an Inverse Regulation of Steroidogenic Acute Regulatory Protein Messenger Ribonucleic Acid in Theca Interna and Granulosa Cells of Equine Preovulatory Follicles Endocrinology, February 1, 1999; 140(2): 667 - 674. [Abstract] [Full Text]
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K. M. Ogilvie, K. Held Hales, M. E. Roberts, D. Buchanan Hales, and C. Rivier The Inhibitory Effect of Intracerebroventricularly Injected Interleukin 1฿ on Testosterone Secretion in the Rat: Role of Steroidogenic Acute Regulatory Protein Biol Reprod, February 1, 1999; 60(2): 527 - 533. [Abstract] [Full Text] [PDF]
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H. A. LaVoie, J. C. Garmey, and J. D. Veldhuis Mechanisms of Insulin-Like Growth Factor I Augmentation of Follicle-Stimulating Hormone-Induced Porcine Steroidogenic Acute Regulatory Protein Gene Promoter Activity in Granulosa Cells Endocrinology, January 1, 1999; 140(1): 146 - 153. [Abstract] [Full Text]
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X. Wang, Z. Liu, S. Eimerl, R. Timberg, A. M. Weiss, J. Orly, and D. M. Stocco Effect of Truncated Forms of the Steroidogenic Acute Regulatory Protein on Intramitochondrial Cholesterol Transfer Endocrinology, September 1, 1998; 139(9): 3903 - 3912. [Abstract] [Full Text] [PDF]
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