This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted 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 Barni, T. Articles by Vannelli, G. B. Search for Related Content PubMed PubMed Citation Articles by Barni, T. Articles by Vannelli, G. B.

Sex Steroids and Odorants Modulate Gonadotropin-Releasing Hormone Secretion in Primary Cultures of Human Olfactory Cells¹

Departments of Human Anatomy and Histology (T.B., G.F., M.G., G.C.B., G.B.V.) and Clinical Physiopathology, Endocrinology (S.G., R.M., E.M., M.L., C.R., M.S.) and Andrology (M.M.) Units, Institute of Internal Medicine (F.M.), University of Florence, 50134 Florence, Italy

Address all correspondence and requests for reprints to: Gabriella B. Vannelli, M.D., Department of Human Anatomy and Histology, University of Florence, Violex Morgagni 85, 50134 Florence, Italy. E-mail: vannelli{at}cesit1.unifi.it

Olfactory neurons and GnRH neurons share a common origin during development. In the nasal epithelia, GnRH neurons persist throughout fetal life and adulthood. The fate and function of these neurons in vivo have remained unknown. In a previous in vitro study, we isolated, cloned, and propagated primary long term cell cultures from the olfactory neuroepithelium of 8- to 12-week-old human fetuses. These cells expressed both neural proteins as well as olfactory genes and were responsive to odorant stimuli. We now report that these human olfactory cells also express the GnRH gene and protein. Combined HPLC and RIA studies have indicated that these cells release authentic GnRH in spent media. The release of GnRH was time dependent and was positively affected by sex steroids and odorants. Immunohistochemical data demonstrated the presence of sex steroid receptors in these cells. The presence of the - and ß-subtypes of the estrogen receptor was also demonstrated by RT-PCR and Western blot analysis. When the cells were stimulated with increasing concentrations of 17ß-estradiol in the presence of a fixed concentration of progesterone (10^-7 mol/L), the combination of the two steroids induced a 3- to 4-fold increase in GnRH secretion. This stimulatory effect was completely blunted by tamoxifen. Neither 17ß-estradiol nor progesterone was effective when tested separately. Treatment with increasing concentrations of the odorant, l-carvone, induced a time- and dose-dependent dramatic increase in GnRH protein release (1000-fold increase) and gene expression. Repeated application of the stimulus resulted in a progressive lower responsiveness of the cells. To our knowledge, this is the first time that primary cell cultures from human fetal olfactory neuroepithelium have been shown to express and release GnRH. Our results also demonstrate that these cultures, which are sensitive to sex steroids and odorants, can be useful models in the study of the complex array of regulatory factors that finely tune GnRH secretion in humans.

This article has been cited by other articles:

				H. Pick, S. Etter, O. Baud, R. Schmauder, L. Bordoli, T. Schwede, and H. Vogel Dual Activities of Odorants on Olfactory and Nuclear Hormone Receptors J. Biol. Chem., October 30, 2009; 284(44): 30547 - 30555. [Abstract] [Full Text] [PDF]

				A. Peri and M. Serio Neuroprotective effects of the Alzheimer's disease-related gene seladin-1 J. Mol. Endocrinol., November 1, 2008; 41(5): 251 - 261. [Abstract] [Full Text] [PDF]

				P. Luciani, C. Deledda, F. Rosati, S. Benvenuti, I. Cellai, F. Dichiara, M. Morello, G. B. Vannelli, G. Danza, M. Serio, et al. Seladin-1 Is a Fundamental Mediator of the Neuroprotective Effects of Estrogen in Human Neuroblast Long-Term Cell Cultures Endocrinology, September 1, 2008; 149(9): 4256 - 4266. [Abstract] [Full Text] [PDF]

				C. K. Cheng and P. C. K. Leung Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans Endocr. Rev., April 1, 2005; 26(2): 283 - 306. [Abstract] [Full Text] [PDF]

				S. Benvenuti, P. Luciani, G. B. Vannelli, S. Gelmini, E. Franceschi, M. Serio, and A. Peri Estrogen and Selective Estrogen Receptor Modulators Exert Neuroprotective Effects and Stimulate the Expression of Selective Alzheimer's Disease Indicator-1, a Recently Discovered Antiapoptotic Gene, in Human Neuroblast Long-Term Cell Cultures J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1775 - 1782. [Abstract] [Full Text] [PDF]

				N. Pitteloud, J. S. Acierno Jr., A. U. Meysing, A. A. Dwyer, F. J. Hayes, and W. F. Crowley Jr. Reversible Kallmann Syndrome, Delayed Puberty, and Isolated Anosmia Occurring in a Single Family with a Mutation in the Fibroblast Growth Factor Receptor 1 Gene J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1317 - 1322. [Abstract] [Full Text] [PDF]

				B.-S. An, J.-H. Choi, K.-C. Choi, and P. C. K. Leung Differential Role of Progesterone Receptor Isoforms in the Transcriptional Regulation of Human Gonadotropin-Releasing Hormone I (GnRH I) Receptor, GnRH I, and GnRH II J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1106 - 1113. [Abstract] [Full Text] [PDF]

				R. G. Romanelli, T. Barni, M. Maggi, M. Luconi, P. Failli, A. Pezzatini, E. Pelo, F. Torricelli, C. Crescioli, P. Ferruzzi, et al. Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons: AN AUTOCRINE GnRH LOOP UNDERLIES NEURONAL MIGRATION J. Biol. Chem., January 2, 2004; 279(1): 117 - 126. [Abstract] [Full Text] [PDF]

				C. Crescioli, M. Maggi, G. B. Vannelli, P. Ferruzzi, S. Granchi, R. Mancina, M. Muratori, G. Forti, M. Serio, and M. Luconi Expression of Functional Estrogen Receptors in Human Fetal Male External Genitalia J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1815 - 1824. [Abstract] [Full Text] [PDF]

				S. Filippi, M. Luconi, S. Granchi, L. Vignozzi, S. Bettuzzi, P. Tozzi, F. Ledda, G. Forti, and M. Maggi Estrogens, But Not Androgens, Regulate Expression and Functional Activity of Oxytocin Receptor in Rabbit Epididymis Endocrinology, November 1, 2002; 143(11): 4271 - 4280. [Abstract] [Full Text] [PDF]

				M. Maggi, T. Barni, G. Fantoni, R. Mancina, C. Pupilli, M. Luconi, C. Crescioli, M. Serio, and G. B. Vannelli Expression and Biological Effects of Endothelin-1 in Human Gonadotropin-Releasing Hormone-Secreting Neurons J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1658 - 1665. [Abstract] [Full Text]