Association of luteinizing hormone receptor gene expression with cell cycle progression in granulosa cells

• Published in: American journal of physiology: endocrinology and metabolism Vol. 296; no. 6; pp. E1392 - E1399
• Main Authors: Cannon, Jennifer D, Seekallu, Srinivas V, VandeVoort, Catherine A, Chaffin, Charles L
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.06.2009
• Subjects: Animals; Cell cycle; Cell Division - drug effects; Cell Division - physiology; Cell Line, Tumor; Cells; Chorionic Gonadotropin - pharmacology; Colforsin - pharmacology; Female; G1 Phase - drug effects; G1 Phase - physiology; Gene expression; Gene Expression Regulation - physiology; Genes; Gonadotropins, Equine - pharmacology; Granulosa Cells - cytology; Granulosa Cells - drug effects; Granulosa Cells - physiology; Hormones; Leydig Cell Tumor; Macaca mulatta; Male; Mice; Mimosine - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, LH - genetics; Ribonucleic acid; RNA; RNA, Messenger - metabolism; S Phase - drug effects; S Phase - physiology; Testicular Neoplasms
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.90965.2008

1 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, Maryland; 2 Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and 3 California National Primate Research Center, University of California, Davis, California Submitted 1 December 2008 ; accepted in final form 14 March 2009 During hormonally induced ovarian follicle growth, granulosa cell proliferation increases and returns to baseline prior to the administration of an ovulatory stimulus. Several key genes appear to follow a similar pattern, including the luteinizing hormone receptor (LHCGR), suggesting an association between cell cycle progression and gene expression. The expression of LHCGR mRNA in granulosa cells isolated from immature rats and treated in culture with FSH increased in a time-dependent manner, whereas administration of the cell cycle inhibitor mimosine completely suppressed expression. Although forskolin was able to induce luteinization in cells treated with mimosine, human chorionic gonadotropin had no effect, indicating the functional loss of LHCGR. The effects of mimosine on cell cycle progression and LHCGR mRNA expression were reversible within 24 h of mimosine removal. Cell cycle inhibition did not alter the stability of LHCGR mRNA, indicating that the primary effect was at the transcriptional level. To determine whether the relationship between LHCGR expression and cell cycle were relevant in vivo, immature rats were given a bolus of PMSG, followed by a second injection of either saline or PMSG 24 h later to augment levels of proliferation. The expression of LHCGR mRNA was elevated in the ovaries of animals receiving a supplement of PMSG. Mimosine also blocked cell cycle progression and LHCGR mRNA expression in macaque granulosa cells isolated following controlled ovarian stimulation cycles and in two different mouse Leydig tumor lines. These data collectively indicate that LHCGR mRNA is expressed as a function of the passage of cells across the G1-S phase boundary. granulosa cell; gene expression; ovary; proliferation Address for reprint requests and other correspondence: C. L. Chaffin, Dept. of Obstetrics, Gynecology, & Reproductive Sciences, Univ. of Maryland School of Medicine, Baltimore, MD 21201 (e-mail: cchaffin{at}upi.umaryland.edu )