Endocrinology, Vol 135, 569-575, Copyright © 1994 by Endocrine Society

ARTICLES

Mesenchymal-epithelial interactions in the ovarian follicle involve keratinocyte and hepatocyte growth factor production by thecal cells and their action on granulosa cells

JA Parrott, JL Vigne, BZ Chu and MK Skinner
Reproductive Endocrinology Center, University of California, San Francisco 94143-0556.

Mesenchymal-epithelial cell interactions between thecal and granulosa cells in bovine ovarian follicles were investigated. Experiments were designed to examine the local production and action of two mesenchymal (stromal)-derived growth factors, keratinocyte and hepatocyte growth factors (KGF and HGF). Using reverse transcription-polymerase chain reaction, gene expression for KGF and HGF was detected in the mesenchymal-derived thecal cells, but not in the epithelial granulosa cells. The bovine polymerase chain reaction products for KGF and HGF were sequenced and found to be similar to known mouse, rat, and human sequences. The bovine KGF sequence was found to have a high degree of identity (86-95%) with the other species, whereas bovine HGF has a lesser degree of identity (60-63%). Immunoprecipitation of radiolabeled thecal cell secreted proteins with a KGF antibody demonstrated production of the 28-kilodalton (kDa) KGF protein. An immunoblot of thecal cell secreted proteins with HGF antibodies detected the 87-kDa HGF as well as relevant 69- and 34-kDa subunits. Therefore, thecal cells were found to express the genes and secrete the proteins for KGF and HGF. Granulosa cells had no detectable KGF or HGF expression. Treatment with recombinant KGF or HGF stimulated the proliferation of granulosa cells, but not thecal cells. Therefore, the actions of KGF and HGF in the ovarian follicle appear to be restricted to granulosa cells. The combined results indicate that KGF and HGF are produced locally in the bovine ovarian follicle by thecal cells, and that both of these growth factors can act on granulosa cells to influence cell proliferation. These observations demonstrate that KGF and HGF can mediate mesenchymal-epithelial cell interactions between thecal and granulosa cells. The potential importance that the mesenchymal derived thecal cells may have in ovarian follicle development is discussed.

This article has been cited by other articles:

				D. Schams, V. Steinberg, M. Steffl, H. H D Meyer, and B. Berisha Expression and possible role of fibroblast growth factor family members in porcine antral follicles during final maturation Reproduction, July 1, 2009; 138(1): 141 - 149. [Abstract] [Full Text] [PDF]

				R. Zachow and M. Uzumcu The hepatocyte growth factor system as a regulator of female and male gonadal function J. Endocrinol., December 1, 2007; 195(3): 359 - 371. [Abstract] [Full Text] [PDF]

				J Buratini Jr., M.G.L Pinto, A.C Castilho, R.L Amorim, I.C Giometti, V.M Portela, E.S Nicola, and C.A Price Expression and Function of Fibroblast Growth Factor 10 and Its Receptor, Fibroblast Growth Factor Receptor 2B, in Bovine Follicles Biol Reprod, October 1, 2007; 77(4): 743 - 750. [Abstract] [Full Text] [PDF]

				A. E. Drummond, M. Tellbach, M. Dyson, and J. K. Findlay Fibroblast Growth Factor-9, a Local Regulator of Ovarian Function Endocrinology, August 1, 2007; 148(8): 3711 - 3721. [Abstract] [Full Text] [PDF]

				M. Uzumcu, Z. Pan, Y. Chu, P. E Kuhn, and R. Zachow Immunolocalization of the hepatocyte growth factor (HGF) system in the rat ovary and the anti-apoptotic effect of HGF in rat ovarian granulosa cells in vitro. Reproduction, August 1, 2006; 132(2): 291 - 299. [Abstract] [Full Text] [PDF]

				H. Shiina, T. Matsumoto, T. Sato, K. Igarashi, J. Miyamoto, S. Takemasa, M. Sakari, I. Takada, T. Nakamura, D. Metzger, et al. From the Cover: Premature ovarian failure in androgen receptor-deficient mice PNAS, January 3, 2006; 103(1): 224 - 229. [Abstract] [Full Text] [PDF]

				P. Kezele, E. E. Nilsson, and M. K. Skinner Keratinocyte Growth Factor Acts as a Mesenchymal Factor That Promotes Ovarian Primordial to Primary Follicle Transition Biol Reprod, November 1, 2005; 73(5): 967 - 973. [Abstract] [Full Text] [PDF]

				S. Lenie, R. Cortvrindt, T. Adriaenssens, and J. Smitz A Reproducible Two-Step Culture System for Isolated Primary Mouse Ovarian Follicles as Single Functional Units Biol Reprod, November 1, 2004; 71(5): 1730 - 1738. [Abstract] [Full Text] [PDF]

				R. Wu, K. H. Van der Hoek, N. K. Ryan, R. J. Norman, and R. L. Robker Macrophage contributions to ovarian function Hum. Reprod. Update, March 1, 2004; 10(2): 119 - 133. [Abstract] [Full Text] [PDF]

				S. Oomizu, K. Chaturvedi, and D. K. Sarkar Folliculostellate Cells Determine the Susceptibility of Lactotropes to Estradiol's Mitogenic Action Endocrinology, March 1, 2004; 145(3): 1473 - 1480. [Abstract] [Full Text] [PDF]

				E. E. Nilsson and M. K. Skinner Bone Morphogenetic Protein-4 Acts as an Ovarian Follicle Survival Factor and Promotes Primordial Follicle Development Biol Reprod, October 1, 2003; 69(4): 1265 - 1272. [Abstract] [Full Text] [PDF]

				Q. Wu, S. Sucheta, S. Azhar, and K. M. J. Menon Lipoprotein Enhancement of Ovarian Theca-Interstitial Cell Steroidogenesis: Relative Contribution of Scavenger Receptor Class B (Type I) and Adenosine 5'-Triphosphate- Binding Cassette (Type A1) Transporter in High-Density Lipoprotein-Cholesterol Transport and Androgen Synthesis Endocrinology, June 1, 2003; 144(6): 2437 - 2445. [Abstract] [Full Text] [PDF]

				R. J. Zachow and J. K. Woolery Effects of Hepatocyte Growth Factor on Cyclic Nucleotide-Dependent Signaling and Steroidogenesis in Rat Ovarian Granulosa Cells In Vitro Biol Reprod, August 1, 2002; 67(2): 454 - 459. [Abstract] [Full Text] [PDF]

				N. Auersperg, A. S. T. Wong, K.-C. Choi, S. K. Kang, and P. C. K. Leung Ovarian Surface Epithelium: Biology, Endocrinology, and Pathology Endocr. Rev., April 1, 2001; 22(2): 255 - 288. [Abstract] [Full Text]

				E. Nilsson and M. K. Skinner Cellular Interactions That Control Primordial Follicle Development and Folliculogenesis Reproductive Sciences, January 1, 2001; 8(1_suppl): S17 - S20. [Abstract] [PDF]

				R. J. Zachow, B. E. Ramski, and H. Lee Modulation of Estrogen Production and 17{beta}-Hydroxysteroid Dehydrogenase-Type 1, Cytochrome P450 Aromatase, c-Met, and Protein Kinase B{alpha} Messenger Ribonucleic Acid Content in Rat Ovarian Granulosa Cells by Hepatocyte Growth Factor and Follicle-Stimulating Hormone Biol Reprod, June 1, 2000; 62(6): 1851 - 1857. [Abstract] [Full Text]

				R. Z. Spaczynski, A. Arici, and A. J. Duleba Tumor Necrosis Factor-{alpha} Stimulates Proliferation of Rat Ovarian Theca-Interstitial Cells Biol Reprod, October 1, 1999; 61(4): 993 - 998. [Abstract] [Full Text]

				L. M. Senturk, E. Seli, L. S. Gutierrez, G. Mor, H. B. Zeyneloglu, and A. Arici Monocyte chemotactic protein-1 expression in human corpus luteum Mol. Hum. Reprod., August 1, 1999; 5(8): 697 - 702. [Abstract] [Full Text] [PDF]

				Y. Osuga, O. Tsutsumi, M. Momoeda, R. Okagaki, H. Matsumi, H. Hiroi, A. Suenaga, T. Yano, and Y. Taketani Evidence for the presence of hepatocyte growth factor expression in human ovarian follicles Mol. Hum. Reprod., August 1, 1999; 5(8): 703 - 707. [Abstract] [Full Text] [PDF]

				D. Chamoun, M. D. DeMoura, E. Levitas, C. E. Resnick, S. E. Gargosky, R. G. Rosenfeld, T. Matsumoto, and E. Y. Adashi Transcriptional and Posttranscriptional Regulation of Intraovarian Insulin-Like Growth Factor-Binding Proteins by Interleukin-1{beta} (IL-1{beta}): Evidence for IL-1{beta} as an Antiatretic Principal Endocrinology, August 1, 1999; 140(8): 3488 - 3495. [Abstract] [Full Text]

				S. Hess, R. Gulati, and J. J. Peluso Hepatocyte Growth Factor Induces Rat Ovarian Surface Epithelial Cell Mitosis or Apoptosis Depending on the Presence or Absence of an Extracellular Matrix Endocrinology, June 1, 1999; 140(6): 2908 - 2916. [Abstract] [Full Text]

				A. J. Duleba, R. Z. Spaczynski, A. Arici, R. Carbone, and H. R. Behrman Proliferation and Differentiation of Rat Theca-Interstitial Cells: Comparison of Effects Induced by Platelet-Derived Growth Factor and Insulin-Like Growth Factor-I Biol Reprod, March 1, 1999; 60(3): 546 - 550. [Abstract] [Full Text]

				U. Salli, F.F. Bartol, A.A. Wiley, B.J. Tarleton, and T.D. Braden Keratinocyte Growth Factor Expression by the Bovine Corpus Luteum Biol Reprod, July 1, 1998; 59(1): 77 - 83. [Abstract] [Full Text]

				J. A. Parrott and and M. K. Skinner Developmental and Hormonal Regulation of Hepatocyte Growth Factor Expression and Action in the Bovine Ovarian Follicle Biol Reprod, July 1, 1998; 59(3): 553 - 560. [Abstract] [Full Text]

				J. Gubbay, J. P. Doyle, M. Skinner, and N. Heintz Changing Patterns of Gene Expression Identify Multiple Steps During Regression of Rat Prostate in Vivo Endocrinology, June 1, 1998; 139(6): 2935 - 2943. [Abstract] [Full Text] [PDF]

				M. Lail-Trecker, R. Gulati, and J. J. Peluso A Role for Hepatocyte Growth Factors/Scatter Factor in Regulating Normal and Neoplastic Cells of Reproductive Tissues Reproductive Sciences, May 1, 1998; 5(3): 114 - 121. [Abstract] [PDF]

				J. A. Parrott and M. K. Skinner Thecal Cell-Granulosa Cell Interactions Involve a Positive Feedback Loop among Keratinocyte Growth Factor, Hepatocyte Growth Factor, and Kit Ligand during Ovarian Follicular Development Endocrinology, May 1, 1998; 139(5): 2240 - 2245. [Abstract] [Full Text] [PDF]

				V. K. Pedchenko and W. T. Imagawa Mammogenic Hormones Differentially Modulate Keratinocyte Growth Factor (KGF)-Induced Proliferation and KGF Receptor Expression in Cultured Mouse Mammary Gland Epithelium Endocrinology, May 1, 1998; 139(5): 2519 - 2526. [Abstract] [Full Text] [PDF]

				J. A. Parrott and M. K. Skinner Developmental and Hormonal Regulation of Keratinocyte Growth Factor Expression and Action in the Ovarian Follicle Endocrinology, January 1, 1998; 139(1): 228 - 235. [Abstract] [Full Text] [PDF]

				M. L. Casey and P. C. MacDonald Keratinocyte Growth Factor Expression in the Mesenchymal Cells of Human Amnion J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3319 - 3323. [Abstract] [Full Text] [PDF]

				J. A. Parrott and M. K. Skinner Direct Actions of Kit-Ligand on Theca Cell Growth and Differentiation During Follicle Development Endocrinology, September 1, 1997; 138(9): 3819 - 3827. [Abstract] [Full Text] [PDF]

				R. Gulati and J. J. Peluso Opposing Actions of Hepatocyte Growth Factor and Basic Fibroblast Growth Factor on Cell Contact, Intracellular Free Calcium Levels, and Rat Ovarian Surface Epithelial Cell Viability Endocrinology, May 1, 1997; 138(5): 1847 - 1856. [Abstract] [Full Text] [PDF]

				R. J. Zachow, S. R. Weitsman, and D. A. Magoffin Hepatocyte Growth Factor Regulates Ovarian Theca-Interstitial Cell Differentiation and Androgen Production Endocrinology, February 1, 1997; 138(2): 691 - 697. [Abstract] [Full Text] [PDF]