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This Article Full Text Full Text (PDF) All Versions of this Article: 71/2/579    most recent biolreprod.104.027300v1 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 My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rao, Ch.V. Articles by Lei, Z.M. Search for Related Content PubMed PubMed Citation Articles by Rao, Ch.V. Articles by Lei, Z.M. Agricola Articles by Rao, Ch.V. Articles by Lei, Z.M.

Functional Luteinizing Hormone/Chorionic Gonadotropin Receptors in Human Adrenal Cortical H295R Cells

Division of Research, Department of Obstetrics, Gynecology and Women's Health, University of Louisville Health Sciences Center, Louisville, Kentucky 40292

Previous studies have suggested that activation of normal human adrenal and adrenal tumor luteinizing hormone (LH)/chorionic gonadotropin (hCG) receptors results in an increased secretion of steroid hormones. Since it is not feasible to test this suggestion on normal human adrenal cells, we used human adrenal cortical carcinoma H295R cells, which are similar in some respects to normal adrenal cortical cells. These cells contained LH/hCG receptor transcripts and receptor protein that can bind ¹²⁵I-hCG in a hormone-specific manner. Culturing the cells with highly purified hCG resulted in a time- and dose-dependent significant increase in dehydroepiandrosterone sulfate (DHEAS) secretion as compared with the controls. The DHEAS response was hormone as well as steroid specific. Since hCG treatment did not increase DHEA secretion, we suspected that the hCG might increase DHEA sulfotransferase (ST). Consistent with this possibility, hCG treatment increased steady-state DHEA-ST mRNA levels. The hCG effects require its receptors, as inhibition of their synthesis by treatment with antisense phosphorothioate oligodeoxynucleotides (ODN) made from the LH/hCG receptor sequence resulted in loss of DHEA-ST and DHEAS responses. The findings that 1) hCG treatment increased cAMP levels and activated protein kinase A (PKA), 2) 8-bromo cAMP mimicked hCG, and 3) blocking PKA activation prevented hCG as well as 8-bromo cAMP from increasing both DHEA-ST mRNA and DHEAS levels suggested that cAMP/PKA signaling was involved in the hCG actions. In conclusion, H295R cells contain LH/hCG receptors, which are coupled to increasing DHEAS secretion through upregulating the ST enzyme mRNA level. This action is mediated by the cAMP/PKA signaling pathway. These findings support the concept that adrenal function in normal and pathological conditions could be influenced by LH and hCG.

¹ Correspondence: Ch. V. Rao, Division of Research, Department of Obstetrics, Gynecology, and Women's Health, 438 MDR Building, 511 South Floyd St., University of Louisville Health Sciences Center, Louisville, KY 40292. FAX: 502 852 0881; cvrao001{at}gwise.louisville.edu

² Current address: Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30322

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