Use of GnRH in preference to LH-RH terminology in scientific papers

Andrew V. Schally

Professor of Medicine, Head, Section of Experimental Medicine, Tulane University School of Medicine, Chief, Endocrine, Polypeptide, and Cancer Institute, The Veterans Affairs Medical Center, New Orleans, Louisiana, USA Distinguished Medical Research Scientist, Department of Veteran Affairs Nobel Prize in Medicine, 1977

Dear Sir,

I was disappointed by your recommendation to use GnRH in preferene to LH-RH.

As you probably know, the official journals of the Endocrine Society, Endocrinology and Journal of Clinical Endocrinology and Metabolism (JCEM) allow the use of both names and abbreviations, i.e. GnRH as well as LH-RH. All the other top journals in this field that specialise in peptides, including Peptides itself and Regulatory Peptides, and even the prestigious Proceedings of the National Academy of Sciences all allow LH-RH and GnRH. The European Journal of Endocrinology and other European journals also permit LH-RH.

In our previous articles published in Human Reproduction (Emons and Schally, 1994Go; Reissmann et al., 1994Go, 1995Go; Gonzales-Barcena et al., 1997) the name luteinizing hormone-releasing hormone and the abbreviation LH-RH were allowed. The terminology of gonadotrophin releasing hormone versus luteinizing hormone releasing hormone for the analogues of LH-RH has been the subject of my various articles and Letters to the Editors for the past years (Schally et al., 1971aGo, 1972Go; Schally and McCann, 1995Go; Schally, 1999aGo). The name lulliliberin proposed by IUPAC (International Union of Pure and Applied Chemistry) was not accepted by the Endocrine Society and is not used.

As you know, in 1971 my laboratory was the first to accomplish the isolation, elucidation of structure and synthesis of hypothalamic LH-RH, winning the race with other groups (Baba et al., 1971Go; Matsuo et al., 1971aGo,bGo; Schally et al., 1971aGo,bGo,cGo,dGo,eGo,fGo). Because both natural LH-RH and synthetic decapeptide corresponding to its structure possessed major FSH-releasing as well as LH-releasing activity, we put forward a concept that one hypothalamic hormone, designated LH-RH/FSH-RH or simply gonadotrophin releasing hormone (GnRH), controls the secretion of both gonadotrophins from the pituitary gland (Schally et al., 1971dGo). The expression gonadotrophin releasing hormone was thus first used in our article (Schally et al., 1971dGo) reporting the structure of LH-RH. The expression gonadotrophin-releasing hormone was used again in another article on confirmation of structure (Nair and Schally, 1972Go). The abbreviation GnRH may have been used for the first time in my article on isolation and structure of LH and FSH releasing hormone (Schally et al., 1971aGo), which was kindly invited by yourselves. The concept formulated by us, that one hypothalamic hormone regulates the secretion of both gonadotrophins from the pituitary gland, is now supported by much experimental and clinical evidence and LH-RH is now accepted as the main FSH-releasing hormone (Schally et al., 1972Go; Schally, 1999aGo,bGo). However, the abbreviation GnRH for gonadotrophin-releasing hormone is confusing, since it is too similar to GH-RH (growth hormone-releasing hormone, for which many agnostic and antagonistic analogues already exist (Schally and Varga, 1999Go). GH-RH and its analogues are of great importance in many areas of endocrinology and may also be involved in reproductive medicine (Bagnato et al., 1992Go; Ciampani et al., 1992Go; Schally and Varga, 1999Go). Thus, it has been demonstrated that endogenous GH-RH enhances the actions of FSH on granulosa cell differentiation (Bagnato et al., 1992Go). It was also shown that GH-RH is produced by rat Leydig cell and acts as a positive regulator of Leydig cell function (Ciampani et al., 1992Go). GH has been used in IVF–embryo transfer methods and agonistic analogues of GH-RH may be also employed. In addition, there are already antagonists of GH-RH, which should have important uses in oncology as tumour inhibitors (Schally and Varga, 1999Go). The abbreviation GnRH is creating confusion not only in discussion but also in the literature and might even lead to accidents. A few years ago, the Food and Drug Administration sent a memorandum meaning LH-RH or GnRH, but they wrote GH-RH. As a matter of fact, we warned 29 years ago, that the abbreviation GnRH may prove troublesome because it is too similar to GH-RH (Schally et al., 1972Go) and would lead to a communication failure to clearly distinguish between these two hormones.

Because I led a team that was the first to isolate LH-RH in the pure state, determine its structure, synthesise it, and carry out original physiological and collaborative clinical studies, I believe that I should be allowed to express my views about its nomenclature. Although we were the first to propose the name gonadotrophin-releasing hormone, abbreviated to GnRH in 1971 (Schally et al., 1971aGo,dGo), much confusion is caused by this abbreviation for those also working on GH-RH analogues. Thus, I again recommend that the abbreviation GnRH should be discontinued, at least for the analogues, and LH-RH be used instead, as it already is by many investigators. Because this proposal may not be accepted by many of those working in this field, who like convenient abbreviations, at least an option should be given to those who are purists at heart to use the nomenclature based on LH-RH.

References

Baba, Y., Matuso, H. and Schally, A.V. (1971) Structure of the porcine LH- and FSH-releasing hormone. II. Confirmation of the proposed structure by conventional sequential analysis. Biochem Biophys Res Commun., 44, 459–463.[ISI][Medline]

Bagnato, A., Costanzo, M., Ohnishi, J. et al. (1992) Expression of the growth hormone-releasing hormone gene and its peptide product in the rat ovary. Endocrinology, 130, 1097–1102.[Abstract]

Ciampani, T., Fabbri, A. , Isidori, A. and Dufau, M.L. (1992) Growth hormone-releasing hormone is produced by rat Leydig cell in culture and acts as a positive regulator of Leydig cell function. Endocrinology, 131, 2785–2792.[Abstract]

Emons, G. and Schally, A.V. (1994) The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers. Hum. Reprod., 9, 1364–1369.[Abstract]

Gonzalez-Barcena, D., Alvarez, E.P.O., Cornejo, I.C. et al. (1997) Treatment of uterine leiomyomas with luteinizing hormone-releasing hormone antagonist Cetrorelix. Hum. Reprod., 12, 2028–2035.[Abstract]

Matsuo, H., Arimura, A. and Schally, A.V. (1971a) Synthesis of the porcine LH- and FSH-releasing hormone by the solid-phase method. Biochem. Biophys. Res. Commun., 45, 822–827.[ISI][Medline]

Matsuo, H., Baba, Y., Nair, R.M.G. et al. (1971b) Structure of the porcine LH- and FSH-releasing hormone. I. The proposed amino acid sequence. Biochem. Biophys. Res. Commun., 43, 1334–1339.[ISI][Medline]

Nair, R.M.G. and Schally, A.V. (1972) Structure of a hypothalamic peptide possessing gonadotropin-releasing activity. Int. J. Peptide Protein Res., 4, 421–430.[ISI][Medline]

Reissmann, Th., Diedrich, K., Comaru-Schally, A.M. and Schally, A.V. (1994) Introduction of LH-RH-antagonists into the treatment of gynaecological disorders. Hum. Reprod., 9, 767–768.[ISI]

Reissmann, Th., Felberbaum, R., Diedrich, K. et al. (1995) Development and applications of luteinizing hormone-releasing hormone antagonists in the treatment of infertility. Hum. Reprod., 10, 1974–1981.[Abstract]

Schally, A.V., Arimura, A. and Kastin, A.J. (1971a) Isolation, structural determination and synthesis of hypothalamic LH and FSH releasing hormone. Res. Reprod., 3, 1.

Schally, A.V., Arimura, A., Baba, Y. et al. (1971b) Purification and properties of the LH and FSH- releasing hormone from porcine hypothalamai. Program of the 53rd meeting of the Endocrine Society, San Francisco, California, June 24–26, Abstract no.55, p. A70.

Schally, A.V., Arimura, A., Baba, Y. et al. (1971c) Isolation and properties of the FSH- and LH-releasing hormone. Biochem. Biophys. Res. Commun., 43, 393–399.[ISI][Medline]

Schally, A.V., Arimura, A., Kastin, A.J. et al. (1971d) Gonadotropin-releasing hormone: one polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science, 173, 1036–1038.[ISI][Medline]

Schally, A.V., Kastin, A.J. and Arimura, A. (1971e) Hypothalamic FSH and LH-regulating hormones, structure, physiology, and clinical studies. Fertil. Steril., 22, 703–721.[ISI][Medline]

Schally, A.V., Nair, R.M.G., Redding, T.W. and Arimura, A. (1971f) Isolation of the LH- and FSH-releasing hormone from porcine hypothalamai. J. Biol. Chem., 246, 7230–7236.[Abstract/Free Full Text]

Schally, A.V., Kastin, A.J., and Arimura, A. (1972) FSH-releasing hormone and LH-releasing hormone. Vit. Horm., 30, 83–164.[Medline]

Schally, A.V. and McCann, S.M. (1995) The privileges of a Nobel laureate: letters to the Editor. Fertil. Steril., 64, 452–453.[Medline]

Schally, A.V. (1999a) Luteinizing hormone-releasing hormone analogs: their impact on the control of tumorigenesis. Peptides, 20, 1247–1262.[ISI][Medline]

Schally A.V. (1999b) LH-RH analogues 1: their impact on reproductive medicine. Gynecol. Endocrinol., 13, 401–409.[ISI][Medline]

Schally, A.V. and Varga, J.L. (1999) Antagonistic analogs of growth hormone-releasing hormone: new potential antitumor agents. TEM., 10, 383–390.[Medline]