Endocrinology, Vol 135, 1963-1971, Copyright © 1994 by Endocrine Society

ARTICLES

Hormonal regulation of rat 17 beta-hydroxysteroid dehydrogenase type 1 in cultured rat granulosa cells: effects of recombinant follicle- stimulating hormone, estrogens, androgens, and epidermal growth factor

S Ghersevich, M Poutanen, J Tapanainen and R Vihko
Biocenter Oulu, University of Oulu, Finland.

Ovarian estradiol (E2) production is regulated by complex interaction of different hormones, such as gonadotropins, steroids, and growth factors. Despite the key role of 17 beta-hydroxysteroid dehydrogenase (17HSD) in E2 biosynthesis, little is known about its regulation in the ovary. Recently, we have characterized the structure of rat 17HSD type 1 and demonstrated that its expression is regulated by gonadotropins and diethylstilbestrol (DES) in rat ovary in vivo. In the present study, the hormonal regulation of 17HSD type 1, and the expression of cytochrome P450 aromatase were examined in parallel in cultured granulosa cells obtained from DES-primed immature rats. Under these conditions, the cells show high expression of 17HSD type 1. Both the enzyme activity and 17HSD type 1 messenger RNA expression in these cells decreased over 2 days of culture in serum-free medium. However, recombinant FSH (recFSH) partially prevented the decreases in enzyme activity and messenger RNA expression in a dose-dependent manner. This effect appears to be mediated by a cAMP-dependent pathway. In contrast to recFSH, neither estrogens (DES or E2) nor androgens (testosterone or dihydrotestosterone) alone affected expression of the enzyme in the cultured cells. However, both estrogens and androgens clearly enhanced the effect of recFSH on 17HSD type 1 expression and 17HSD activity in a dose-dependent manner. Among the growth factors, epidermal growth factor (EGF) has previously been shown to decrease the expression of cytochrome P450 aromatase and E2 biosynthesis in granulosa cells. In the present study, we found that treatment with EGF caused a marked decrease in the effect of recFSH on 17HSD type 1 expression and 17HSD activity. The fact that 17HSD type 1 expression and 17HSD activity always behaved in parallel suggests that 17HSD type 1 is the major 17HSD enzyme involved in estradiol biosynthesis in rat granulosa cells. In conclusion, these data indicate that expression of 17HSD type 1 in rat granulosa cells is under multihormonal regulation. The enzyme is regulated by FSH, via cAMP, and the effect of FSH is modulated by estrogens, androgens, and EGF.

This article has been cited by other articles:

				P.-G. Blanchard and V. Luu-The Differential androgen and estrogen substrates specificity in the mouse and primates type 12 17{beta}-hydroxysteroid dehydrogenase J. Endocrinol., August 1, 2007; 194(2): 449 - 455. [Abstract] [Full Text] [PDF]

				C. Stocco, C. Telleria, and G. Gibori The Molecular Control of Corpus Luteum Formation, Function, and Regression Endocr. Rev., February 1, 2007; 28(1): 117 - 149. [Abstract] [Full Text] [PDF]

				J. F. Couse, M. M. Yates, K. F. Rodriguez, J. A. Johnson, D. Poirier, and K. S. Korach The Intraovarian Actions of Estrogen Receptor-{alpha} Are Necessary to Repress the Formation of Morphological and Functional Leydig-Like Cells in the Female Gonad Endocrinology, August 1, 2006; 147(8): 3666 - 3678. [Abstract] [Full Text] [PDF]

				K. L. Britt, P. G. Stanton, M. Misso, E. R. Simpson, and J. K. Findlay The Effects of Estrogen on the Expression of Genes Underlying the Differentiation of Somatic Cells in the Murine Gonad Endocrinology, August 1, 2004; 145(8): 3950 - 3960. [Abstract] [Full Text] [PDF]

				J. F. Couse, M. M. Yates, V. R. Walker, and K. S. Korach Characterization of the Hypothalamic-Pituitary-Gonadal Axis in Estrogen Receptor (ER) Null Mice Reveals Hypergonadism and Endocrine Sex Reversal in Females Lacking ER{alpha} But Not ER{beta} Mol. Endocrinol., June 1, 2003; 17(6): 1039 - 1053. [Abstract] [Full Text] [PDF]

				S.A. Whitehead and M. Lacey Phytoestrogens inhibit aromatase but not 17{beta}-hydroxysteroid dehydrogenase (HSD) type 1 in human granulosa-luteal cells: evidence for FSH induction of 17{beta}-HSD Hum. Reprod., March 1, 2003; 18(3): 487 - 494. [Abstract] [Full Text] [PDF]

				S. Leivonen, Y.-s. Piao, H. Peltoketo, P. Numchaisrika, R. Vihko, and P. Vihko Identification of Essential Subelements in the hHSD17B1 Enhancer: Difference in Function of the Enhancer and That of the hHSD17BP1 Analog Is due to -480C and -486G Endocrinology, August 1, 1999; 140(8): 3478 - 3487. [Abstract] [Full Text]

				D. Haynes-Johnson, M.-T. Lai, C. Campen, and S. Palmer Diverse Effects of Tyrosine Kinase Inhibitors on Follicle-Stimulating Hormone-Stimulated Estradiol and Progesterone Production from Rat Granulosa Cells in Serum-Containing Medium and Serum-Free Medium Containing Epidermal Growth Factor Biol Reprod, July 1, 1999; 61(1): 147 - 153. [Abstract] [Full Text]

				M. V. J. Mustonen, V. V. Isomaa, T. Vaskivuo, J. Tapanainen, M. H. Poutanen, F. Stenbäck, R. K. Vihko, and P. T. Vihko Human 17{beta}-Hydroxysteroid Dehydrogenase Type 2 Messenger Ribonucleic Acid Expression and Localization in Term Placenta and in Endometrium during the Menstrual Cycle J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1319 - 1324. [Abstract] [Full Text]

				F. Otsuka, S. Yamamoto, G. F. Erickson, and S. Shimasaki Bone Morphogenetic Protein-15 Inhibits Follicle-stimulating Hormone (FSH) Action by Suppressing FSH Receptor Expression J. Biol. Chem., March 30, 2001; 276(14): 11387 - 11392. [Abstract] [Full Text] [PDF]