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 Lee, P. S. N. Articles by Leung, P. C. K. Search for Related Content PubMed PubMed Citation Articles by Lee, P. S. N. Articles by Leung, P. C. K.

Intracellular Calcium Mobilization in Response to the Activation of Human Wild-Type and Chimeric Gonadotropin Receptors

Departments of Obstetrics and Gynecology (P.S.N.L., B.H.Y., P.C.K.L.) and Physiology (A.M.J.B.), University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5; and Division of Reproductive Biology, Stanford University Medical Center (A.J.W.H.), Stanford, California 94305

Address all correspondence and requests for reprints to: Dr. Peter C. K. Leung, Department of Obstetrics and Gynecology, University of British Columbia, 2H30-4490 Oak Street, Vancouver, British Columbia, Canada V6H 3V5. E-mail: . peleung{at}interchange.ubc.ca

It is well established that LH action is mediated primarily by adenylate cyclase/cAMP. However, the role of inositol phosphate/calcium in LH signaling is less well established. We examined the effects of gonadotropins in primary culture human granulosa-lutein cells and in HEK293 cells transiently transfected with human wild-type or chimeric gonadotropin receptors. The intracellular free calcium concentration was measured using fura-2 microspectrofluorometric techniques. Human (h) LH (2–4 µg/ml) and CG (10 IU/ml) consistently evoked oscillatory calcium signals in HEK293 cells transfected with hLH receptor, whereas hFSH (2–4 µg/ml) failed to elicit any response. Conversely, both hLH and hFSH failed to elicit a calcium response from HEK293 cells transfected with hFSHR, indicating the specificity of the response to the LH receptor. Pretreatment of transfected HEK293 cells with pertussis toxin (100 ng/ml) attenuated all gonadotropin-evoked calcium mobilization.

Studies with chimeric LH receptor showed that the sequence of the long extracellular portion of the receptor was not critical for stimulation of PLC activity, but maintained agonist binding specificity. The C-terminal sequence of the receptor was clearly important for the generation of the basal calcium oscillations, but the precise extent of the critical sequence has yet to be identified. Although various subdivisions of this region were capable of stimulating calcium transients, an intact carboxyl-terminal third of the receptor was required for normal and sustained intracellular calcium signaling. Our study unequivocally shows that the hLH receptor is coupled to the inositol phosphate/calcium signaling pathway via a pertussis toxin-sensitive G protein-coupled receptor.

This article has been cited by other articles:

				P. Olivero, E. Leiva-Salcedo, L. Devoto, and A. Stutzin Activation of Cl- Channels by Human Chorionic Gonadotropin in Luteinized Granulosa Cells of the Human Ovary Modulates Progesterone Biosynthesis Endocrinology, September 1, 2008; 149(9): 4680 - 4687. [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]

				M. N. Diouf, K. Sayasith, R. Lefebvre, D. W. Silversides, J. Sirois, and J. G. Lussier Expression of Phospholipase A2 Group IVA (PLA2G4A) Is Upregulated by Human Chorionic Gonadotropin in Bovine Granulosa Cells of Ovulatory Follicles Biol Reprod, June 1, 2006; 74(6): 1096 - 1103. [Abstract] [Full Text] [PDF]

				E.V. Younglai, T. K. Kwan, C.-Y. Kwan, D.K. Lobb, and W.G. Foster Dichlorodiphenylchloroethylene Elevates Cytosolic Calcium Concentrations and Oscillations in Primary Cultures of Human Granulosa-Lutein Cells Biol Reprod, June 1, 2004; 70(6): 1693 - 1700. [Abstract] [Full Text] [PDF]

				E. V. Younglai, A. C. Holloway, G. E. Lim, and W. G. Foster Synergistic effects between FSH and 1,1-dichloro-2,2-bis(P-chlorophenyl)ethylene (P,P'-DDE) on human granulosa cell aromatase activity Hum. Reprod., May 1, 2004; 19(5): 1089 - 1093. [Abstract] [Full Text] [PDF]

				S. Dabizzi, I. Noci, P. Borri, E. Borrani, M. Giachi, M. Balzi, G. L. Taddei, M. Marchionni, G. F. Scarselli, and A. Arcangeli Luteinizing Hormone Increases Human Endometrial Cancer Cells Invasiveness through Activation of Protein Kinase A Cancer Res., July 15, 2003; 63(14): 4281 - 4286. [Abstract] [Full Text] [PDF]