This Article Full Text Full Text (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 Donadeu, F. X. Articles by Ascoli, M. Search for Related Content PubMed PubMed Citation Articles by Donadeu, F. X. Articles by Ascoli, M.

The Differential Effects of the Gonadotropin Receptors on Aromatase Expression in Primary Cultures of Immature Rat Granulosa Cells Are Highly Dependent on the Density of Receptors Expressed and the Activation of the Inositol Phosphate Cascade

Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242

Address all correspondence and requests for reprints to: Dr. Mario Ascoli, Department of Pharmacology, Carver College of Medicine, 2-319B BSB, 51 Newton Road, The University of Iowa, Iowa City, Iowa 52242. E-mail: mario-ascoli{at}uiowa.edu.

Signaling pathways mediating the divergent effects of FSH and LH on aromatase in immature rat granulosa cells were studied by infecting cells with increasing amounts of adenoviral vectors for the human LH receptor (hLHR) or FSH receptor (hFSHR). Increasing amounts of Ad-hLHR, used at a multiplicity of infection (MOI) of 20 or 200 viable viral particles/cell, increased human chorionic gonadotropin (hCG) binding and hCG-induced cAMP and Akt phosphorylation, but inositol phosphates only increased in response to hCG in cells infected with 200 MOI Ad-hLHR. In contrast, hCG increased aromatase expression in cells infected with 20, but not in cells infected with 200, MOI Ad-hLHR. Cells infected with 20 or 200 MOI Ad-hFSHR showed increased hFSH binding and hFSH-induced Akt phosphorylation, but the hFSH-induced cAMP response was unchanged relative to control cells. However, hFSH was able to stimulate the inositol phosphate cascade in the Ad-hFSHR-infected cells, and the hFSH induction of aromatase was abolished. We also found that activation of C kinase or expression of a constitutively active form of Gq inhibited the induction of aromatase by hFSH or 8Br-cAMP. We conclude that the differential effects of FSH and LH on aromatase in immature granulosa cells are highly dependent on gonadotropin receptor density and on the signaling pathways activated. We propose that aromatase is induced by common signals generated by activation of the FSHR and LHR (possibly cAMP and Akt) and that the activation of the inositol phosphate cascade in cells expressing a high density of LHR or FSHR antagonizes this induction.

This article has been cited by other articles:

				N. Andric and M. Ascoli The Luteinizing Hormone Receptor-Activated Extracellularly Regulated Kinase-1/2 Cascade Stimulates Epiregulin Release from Granulosa Cells Endocrinology, November 1, 2008; 149(11): 5549 - 5556. [Abstract] [Full Text] [PDF]

				K. Shiraishi and M. Ascoli Lutropin/Choriogonadotropin Stimulate the Proliferation of Primary Cultures of Rat Leydig Cells through a Pathway that Involves Activation of the Extracellularly Regulated Kinase 1/2 Cascade Endocrinology, July 1, 2007; 148(7): 3214 - 3225. [Abstract] [Full Text] [PDF]

				B.K. Campbell, N.R. Kendall, and D.T. Baird The Effect of the Presence and Pattern of Luteinizing Hormone Stimulation on Ovulatory Follicle Development in Sheep Biol Reprod, April 1, 2007; 76(4): 719 - 727. [Abstract] [Full Text] [PDF]

				J M Silva, M Hamel, M Sahmi, and C A Price Control of oestradiol secretion and of cytochrome P450 aromatase messenger ribonucleic acid accumulation by FSH involves different intracellular pathways in oestrogenic bovine granulosa cells in vitro. Reproduction, December 1, 2006; 132(6): 909 - 917. [Abstract] [Full Text] [PDF]

				N. Andric and M. Ascoli A Delayed Gonadotropin-Dependent and Growth Factor-Mediated Activation of the Extracellular Signal-Regulated Kinase 1/2 Cascade Negatively Regulates Aromatase Expression in Granulosa Cells Mol. Endocrinol., December 1, 2006; 20(12): 3308 - 3320. [Abstract] [Full Text] [PDF]

				M. Xu, E. West, L. D. Shea, and T. K. Woodruff Identification of a Stage-Specific Permissive In Vitro Culture Environment for Follicle Growth and Oocyte Development Biol Reprod, December 1, 2006; 75(6): 916 - 923. [Abstract] [Full Text] [PDF]

				A. D. Burkart, A. Mukherjee, and K. E. Mayo Mechanism of Repression of the Inhibin {alpha}-Subunit Gene by Inducible 3',5'-Cyclic Adenosine Monophosphate Early Repressor Mol. Endocrinol., March 1, 2006; 20(3): 584 - 597. [Abstract] [Full Text] [PDF]