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1 June 2000 Modulation of Estrogen Production and 17β-Hydroxysteroid Dehydrogenase-Type 1, Cytochrome P450 Aromatase, c-Met, and Protein Kinase Bα Messenger Ribonucleic Acid Content in Rat Ovarian Granulosa Cells by Hepatocyte Growth Factor and Follicle-Stimulating Hormone
Rob J. Zachow, Brian E. Ramski, Howard Lee
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Abstract

Hepatocyte growth factor (HGF) suppresses FSH-dependent estradiol-17β (E2) production in ovarian granulosa cells (GC). The mechanisms of action for HGF in GC are unknown; however, activation of the HGF receptor, c-Met, can induce c-Akt/protein kinase B (PKB)-mediated signal transduction in nonovarian cells. Using immature rat GC, the present study investigated the effects of HGF within the estrogen biosynthetic pathway, concomitant with changes in c-Met and PKBα mRNA expression. Granulosa cells were incubated with androstenedione and FSH, HGF, and/or dibutyryl-cAMP (Bu2-cAMP). Follicle-stimulating hormone and Bu2-cAMP each stimulated estrone (E1) and E2 synthesis at 48 h. Hepatocyte growth factor suppressed FSH-dependent E2, but not E1, synthesis. Semiquantitative reverse transcription–polymerase chain reaction showed that HGF impaired FSH-supported 17β-hydroxysteroid dehydrogenase type-1 (17β-HSD) and cytochrome P450 aromatase (P450arom) mRNA levels. Hepatocyte growth factor did not reduce E2 synthesis or 17β-HSD and P450arom mRNA expression in the presence of Bu2-cAMP at 48 h. The FSH and HGF each down-modulated c-Met mRNA accumulation, whereas Bu2-cAMP increased c-Met mRNA content. Between 0 and 48 h a biphasic change in PKBα mRNA content occurred with either FSH or HGF; however, PKBα mRNA accumulation was augmented by HGF. Collectively, results suggest that HGF can suppress E2 production in GC by disrupting cAMP-dependent 17β-HSD and P450arom. Changes in c-Met and PKBα mRNA content provide a potential link between HGF signaling and the FSH-dependent mechanisms that control the steroidogenic differentiation of GC.

Rob J. Zachow, Brian E. Ramski, and Howard Lee "Modulation of Estrogen Production and 17β-Hydroxysteroid Dehydrogenase-Type 1, Cytochrome P450 Aromatase, c-Met, and Protein Kinase Bα Messenger Ribonucleic Acid Content in Rat Ovarian Granulosa Cells by Hepatocyte Growth Factor and Follicle-Stimulating Hormone," Biology of Reproduction 62(6), 1851-1857, (1 June 2000). https://doi.org/10.1095/biolreprod62.6.1851
Received: 26 October 1999; Accepted: 1 January 2000; Published: 1 June 2000
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