This Article Full Text Full Text (PDF) All Versions of this Article: 18/8/2085    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Luo, C.-W. Articles by Hsueh, A. J. W. Search for Related Content PubMed PubMed Citation Articles by Luo, C.-W. Articles by Hsueh, A. J. W.

Paracrine Regulation of Ovarian Granulosa Cell Differentiation by Stanniocalcin (STC) 1: Mediation through Specific STC1 Receptors

Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305

Address all correspondence and requests for reprints to: Aaron J. W. Hsueh, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305-5317. E-mail: aaron.hsueh{at}stanford.edu.

Stanniocalcin (STC) in fish maintains calcium and phosphate homeostasis, whereas mammalian STC1 shows a diverse tissue expression pattern with ovary exhibiting the highest level. Based on the known expression of STC1 in theca/interstitial cells of the ovary, we generated recombinant N-glycosylated STC1 protein and tested its ability to modulate granulosa cell differentiation. In cultured rat granulosa cells obtained from early antral follicles, treatment with STC1 suppressed FSH-stimulated progesterone biosynthesis with minimal effects on estradiol and cAMP production. In mature granulosa cells, treatment with STC1 also suppressed human chorionic gonadotropin-induced progesterone production. The inhibitory effect of STC1 was accompanied by a pronounced suppression of the CYP11A transcripts and the FSH induction of functional LH receptors. In addition, STC1 was found to act downstream of adenyl cyclases in suppressing progesterone biosynthesis. We also tested the regulation of STC1 gene expression by gonadotropins. Treatment with pregnant mare serum gonadotropin decreased STC1 transcript levels in theca cells of maturing follicles, whereas subsequent treatment with human chorionic gonadotropin led to sustained suppression in the corpora lutea. Using radiolabeled recombinant STC1, receptor assays showed specific STC1 binding with a high affinity to granulosa cells. Because STC1 is expressed in ovarian theca/interstitial cells, the present demonstration of receptor binding and the specific actions of STC1 in granulosa cells suggest the existence of a follicular paracrine system in which theca cell-derived STC1 dampens the gonadotropin stimulation of granulosa cell differentiation. The observed STC1 suppression of progesterone, but not estradiol, production further suggests the potential role of this paracrine hormone as a luteinization inhibitor.

This article has been cited by other articles:

				S. Raulic, Y. Ramos-Valdes, and G. E DiMattia Stanniocalcin 2 expression is regulated by hormone signalling and negatively affects breast cancer cell viability in vitro J. Endocrinol., June 1, 2008; 197(3): 517 - 529. [Abstract] [Full Text] [PDF]

				P. Zhao, A. De, Z. Hu, J. Li, S. M. Mulders, M. D. Sollewijn Gelpke, E.-K. Duan, and A. J. W. Hsueh Gonadotropin Stimulation of Ovarian Fractalkine Expression and Fractalkine Augmentation of Progesterone Biosynthesis by Luteinizing Granulosa Cells Endocrinology, June 1, 2008; 149(6): 2782 - 2789. [Abstract] [Full Text] [PDF]

				G. Dole, E. E Nilsson, and M. K Skinner Glial-derived neurotrophic factor promotes ovarian primordial follicle development and cell-cell interactions during folliculogenesis Reproduction, May 1, 2008; 135(5): 671 - 682. [Abstract] [Full Text] [PDF]

				K. J Johnson, J. B Hensley, M. D Kelso, D. G Wallace, and K. W Gaido Mapping Gene Expression Changes in the Fetal Rat Testis Following Acute Dibutyl Phthalate Exposure Defines a Complex Temporal Cascade of Responding Cell Types Biol Reprod, December 1, 2007; 77(6): 978 - 989. [Abstract] [Full Text] [PDF]

				S.-H. Hsu and C.-W. Luo Molecular dissection of G protein preference using Gs{alpha} chimeras reveals novel ligand signaling of GPCRs Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1021 - E1029. [Abstract] [Full Text] [PDF]

				K. W. Gaido, J. B. Hensley, D. Liu, D. G. Wallace, S. Borghoff, K. J. Johnson, S. J. Hall, and K. Boekelheide Fetal Mouse Phthalate Exposure Shows that Gonocyte Multinucleation is Not Associated with Decreased Testicular Testosterone Toxicol. Sci., June 1, 2007; 97(2): 491 - 503. [Abstract] [Full Text] [PDF]

				A. Chakraborty, H. Brooks, P. Zhang, W. Smith, M. R. McReynolds, J. B. Hoying, R. Bick, L. Truong, B. Poindexter, H. Lan, et al. Stanniocalcin-1 regulates endothelial gene expression and modulates transendothelial migration of leukocytes Am J Physiol Renal Physiol, February 1, 2007; 292(2): F895 - F904. [Abstract] [Full Text] [PDF]

				A. De, J.-I. Park, K. Kawamura, R. Chen, C. Klein, R. Rauch, S. M. Mulders, M. D. Sollewijn Gelpke, and A. J. W. Hsueh Intraovarian Tumor Necrosis Factor-Related Weak Inducer of Apoptosis/Fibroblast Growth Factor-Inducible-14 Ligand-Receptor System Limits Ovarian Preovulatory Follicles from Excessive Luteinization Mol. Endocrinol., October 1, 2006; 20(10): 2528 - 2538. [Abstract] [Full Text] [PDF]

				G. Song, F. W. Bazer, G. F. Wagner, and T. E. Spencer Stanniocalcin (STC) in the Endometrial Glands of the Ovine Uterus: Regulation by Progesterone and Placental Hormones Biol Reprod, May 1, 2006; 74(5): 913 - 922. [Abstract] [Full Text] [PDF]

				C.-W. Luo, E. M. Dewey, S. Sudo, J. Ewer, S. Y. Hsu, H.-W. Honegger, and A. J. W. Hsueh Bursicon, the insect cuticle-hardening hormone, is a heterodimeric cystine knot protein that activates G protein-coupled receptor LGR2 PNAS, February 22, 2005; 102(8): 2820 - 2825. [Abstract] [Full Text] [PDF]

				C.-W. Luo, M. D. Pisarska, and A. J. W. Hsueh Identification of a Stanniocalcin Paralog, Stanniocalcin-2, in Fish and the Paracrine Actions of Stanniocalcin-2 in the Mammalian Ovary Endocrinology, January 1, 2005; 146(1): 469 - 476. [Abstract] [Full Text] [PDF]

				A. D. Gagliardi, E. Y. W. Kuo, S. Raulic, G. F. Wagner, and G. E. DiMattia Human stanniocalcin-2 exhibits potent growth-suppressive properties in transgenic mice independently of growth hormone and IGFs Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E92 - E105. [Abstract] [Full Text] [PDF]