| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Reproductive Endocrinology Center, University of California, San Francisco, California 94143-0556; and Center for Reproductive Biology, Department of Genetics and Cell Biology, Washington State University, Pullman, Washington 99164-4231
Address all correspondence and requests for reprints to: Michael K. Skinner, Center for Reproductive Biology, Department of Genetics and Cell Biology, Washington State University, Pullman, Washington 99164-4231. E-mail: skinner{at}mail.wsu.edu
The developing ovarian follicle is one of the most rapidly proliferating normal tissues in vivo. Mesenchymal-epithelial cell interactions between theca cells and granulosa cells are essential for this follicular expansion. Ovarian hormones (i.e. estrogen and LH) may promote follicular development by regulating the local production of mesenchymal inducer proteins that mediate theca cell-granulosa cell interactions. Recently, theca cells were shown to produce keratinocyte growth factor (KGF) that can act in a paracrine manner to stimulate granulosa cell growth. In this study, the developmental and hormonal regulation of KGF was examined during follicular development in the bovine ovary. Expression of KGF in theca cells and the KGF receptor (KGFR, or splice variant of the fibroblast growth factor family receptor family, FGFR-2) in granulosa cells was examined using RT-PCR. Both KGF and KGFR were detected throughout follicular development in small (<5 mm), medium (5–10 mm), and large (>10 mm) follicles. Quantitative RT-PCR assays were used to determine steady-state levels of KGF and KGFR messenger RNAs. Developmental regulation of KGF and KGFR was analyzed in freshly isolated theca cells and granulosa cells from small, medium, and large follicles. Observations demonstrated that expression of KGF (in theca cells) and KGFR (in granulosa cells) was highest in large follicles. These results suggest that KGF actions are important for the rapid proliferation of granulosa cells in large follicles. Estrogen and LH are the primary endocrine hormones that regulate theca cell function in vivo. Therefore, hormonal regulation of KGF was analyzed by treating serum-free theca cell cultures with estrogen and human CG (hCG, an LH agonist). Results showed that both estrogen and hCG stimulated KGF gene expression in theca cells. These results suggest that estrogen and LH may promote follicular growth (i.e. granulosa cell proliferation), in part, by stimulating the local production of KGF. Effects of KGF on granulosa cell differentiated functions were examined. Treatment with KGF reduced basal levels and FSH-stimulated levels of aromatase activity in bovine and rat granulosa cells. In addition, KGF inhibited the ability of hCG to stimulate progesterone production by granulosa cells. The inhibition of granulosa cell steroid production by KGF was likely the indirect effect of promoting cellular proliferation. Therefore, KGF directly stimulates granulosa cell proliferation and indirectly inhibits granulosa cell differentiated functions. Combined results suggest that theca cell production of KGF may be important for ovarian folliculogenesis. This is the first report of the regulation of KGF expression in the ovary. The developmental and hormonal regulation of KGF and KGFR during folliculogenesis provides evidence that KGF may be important for hormone-induced granulosa cell proliferation. As a result, KGF may be essential for establishing the microenvironment required for oocyte maturation in the ovary.
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 B. Berisha, M. Steffl, W. Amselgruber, and D. Schams Changes in fibroblast growth factor 2 and its receptors in bovine follicles before and after GnRH application and after ovulation Reproduction, February 1, 2006; 131(2): 319 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Buratini Jr, A B Teixeira, I B Costa, V F Glapinski, M G L Pinto, I C Giometti, C M Barros, M Cao, E S Nicola, and C A Price Expression of fibroblast growth factor-8 and regulation of cognate receptors, fibroblast growth factor receptor-3c and -4, in bovine antral follicles Reproduction, September 1, 2005; 130(3): 343 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I Demeestere, J Centner, C Gervy, Y Englert, and A Delbaere Impact of various endocrine and paracrine factors on in vitro culture of preantral follicles in rodents Reproduction, August 1, 2005; 130(2): 147 - 156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Perry, M. F. Smith, M. C. Lucy, J. A. Green, T. E. Parks, M. D. MacNeil, A. J. Roberts, and T. W. Geary From the Cover: Relationship between follicle size at insemination and pregnancy success PNAS, April 5, 2005; 102(14): 5268 - 5273. [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]
|
|
|
|
 |
|
 F. Taniguchi, T. Harada, Y. Sakamoto, N. Yamauchi, S. Yoshida, T. Iwabe, and N. Terakawa Activation of Mitogen-Activated Protein Kinase Pathway by Keratinocyte Growth Factor or Fibroblast Growth Factor-10 Promotes Cell Proliferation in Human Endometrial Carcinoma Cells J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 773 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Doraiswamy, J. A. Parrott, and M. K. Skinner Expression and Action of Transforming Growth Factor Alpha in Normal Ovarian Surface Epithelium and Ovarian Cancer Biol Reprod, September 1, 2000; 63(3): 789 - 796. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. Parrott, R. Mosher, G. Kim, and M. K. Skinner Autocrine Interactions of Keratinocyte Growth Factor, Hepatocyte Growth Factor, and Kit-Ligand in the Regulation of Normal Ovarian Surface Epithelial Cells Endocrinology, July 1, 2000; 141(7): 2532 - 2539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ka, T. E. Spencer, G. A. Johnson, and F. W. Bazer Keratinocyte Growth Factor: Expression by Endometrial Epithelia of the Porcine Uterus Biol Reprod, June 1, 2000; 62(6): 1772 - 1778. [Abstract] [Full Text]
|
|
|
|
|
|
H. Yada, K. Hosokawa, K. Tajima, Y. Hasegawa, and F. Kotsuji Role of Ovarian Theca and Granulosa Cell Interaction in Hormone Productionand Cell Growth During the Bovine Follicular Maturation Process Biol Reprod, December 1, 1999; 61(6): 1480 - 1486. [Abstract] [Full Text]
|
|
|
|
 |
|
 P Gillis, U Savla, O. Volpert, B Jimenez, C. Waters, R. Panos, and N. Bouck Keratinocyte growth factor induces angiogenesis and protects endothelial barrier function J. Cell Sci., January 6, 1999; 112(12): 2049 - 2057. [Abstract] [PDF]
|
|
|
|
|
|
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. 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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
