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The Privileges of a Nobel Laureate
Vol. 64, No.2, August 1995
FERTILITY AND STERILITY Copyright
0
1995 American Society for Reproductive Medicine
The Privileges of a Nobel Laureate
To the Editor: A recent letter (1) cites the misuse ofthe terminology ofluteinizing hormone-releasing hormone (LHRH) antagonists and a confusion in the scientific literature. We feel that this is caused not by the issues whether LH-RH receptors are "down-regulated" or not by the LH-RH antagonists, but by the problems with the nomenclature for the hypothalamic hormone that causes the liberation of both LH and FSH from the anterior pituitary gland. These problems about the nomenclature ofLH-RH are becoming more and more acute. Because one of us (S.M.M.e.) discovered LH-RH (2) and the other (A.V.S.) led a team that isolated LH-RH in pure state, determined its structure, synthesized it, and carried out original physiological and collaborative clinical studies (3, 4), we believe that we should be allowed to express our views about the nomenclature of LH-RH and the use of the abbreviation GnRH. Having worked not only on LH-RH, but also on somatostatin and growth hormone-releasing hormone (GH-RH) and their analogues, we recommend the use of the abbreviation LH-RH for luteinizing hormone-releasing hormone and GH-RH for growth hormone-releasing hormone. This recommendation was already made in various reviews (5). It is now well known that LH-RH releases FSH in addition to LH, as it was first shown in 1971 (3). One of us (A.V.S.) was, in fact, the first to propose the name gonadotropin-releasing hormone, abbreviated as GnRH in 1971 (3), but much confusion is caused by this abbreviation. Moreover, the secretion of LH and FSH under acute conditions can be dissociated, so that there can be another FSH-RH (6). Growth hormone (GH) is already used in IVF-ET (Assisted Reproductive Technology) methods and agonistic analogues of GHRH may be used soon (6). The abbreviation GnRH is creating confusion not only when speaking, but also in writing and might even lead to accidents. Recently, FDA sent a memorandum meaning LHRH or GnRH, but they wrote GH-RH. In addition, there are already antagonists of GH-RH (6). As a matter of fact, we warned 22 years ago, that the abbreviation GnRH for gonadotropin-releasing hormone will be confusing, because it is too similar to GH-RH (5). In conclusion, because LH-RH agonists and antag452
Letters-to-the-editor
Printed on acid·free paper in U. S. A.
onists are increasingly used in gynecology and oncology, we recommend that the abbreviation GnRH should be discontinued, at least for the analogues, and LH-RH be used instead.
Andrew V. Schally, Ph.D., M.Dhc. Endocrine, Polypeptide, and Cancer Institute VA Medical Center and Department of Medicine Tulane University School of Medicine New Orleans, Louisiana Samuel M. (Don) McCann, M.D. Department of Physiology University of Texas Southwestern Medical Center Dallas, Texas January 11, 1995 REFERENCES 1. Gordon K. Terminology for GnRH antagonists. Fertil Steril 1994;61:994-5. 2. McCann SM, Taleisnik S, Friedman HN. LH releasing activity in hypothalamic extracts. Proc Soc Exp BioI Med 1960; 104:432-4. 3. Schally AV, Arimura A, Kastin AJ, Matsuo H, Baba Y, Redding TW, et al. The gonadotropin-releasing hormone: one polypeptide regulates the secretion ofluteinizing and follicle stimulating hormones. Science 1971; 173:1036-8. 4. Schally AV, Kastin AJ, Arimura A Hypothalamic folliclestimulating hormone (FSH) and luteinizing hormone (LH)regulating hormone: structure, physiology and clinical studies. Fertil Steril 1971;22:703-21. 5. Schally AV, Kastin AJ, Arimura A FSH-releasing hormone and LH-releasing hormone. Vitamins Hormones 1972;30:83164.
Note. Additional other references available upon request.
The author elected not to respond. Paul G. McDonough, M.D., Editor, Letters Editorial Comment The Privileges of a Nobel Laureate
Among the privileges of a Nobel laureate is the right to suggest a proper name or at least an operational name for a substance that one has isolated. The original isolation of luteinizing hormone-releasing hormone (LH-RH) by Andrew Schally required 160,000 porcine hypothalami in order to produce just 250 micrograms of the putative substance. ConsiderFertility and Sterility
ing the limited analytical methods available at the time it is remarkable that the structure of LH-RH was deduced from this small amount of starting material. The final structural analysis and the synthesis of the candidate peptide from this starting material was accomplished by a remarkable Japanese chemist working with Schally by the name of Hisayuki Matsuo. Akira Arimura, a physiologist, was responsible for verifying the biological activity of the newly synthesized LH-RH. Today his task may seem like "a piece of cake," but in 1971 the only available techniques to quantitate the LH and FSH response to the final test material provided by Matsuo were bioassays. These gonadotropin bioassays were difficult, problematic, and plagued with inconsistent results. It was a "twist of fate" that brought Gordon Niswender to his rescue. Doctor Niswender developed and provided to Doctor Arimura the first rabbit antiovine LH antibodies. These antibodies cross-reacted with LH from all mammalian species and were provided by Doctor Niswender under the by line of serum #15. The development of a reliable solid-phase RIA for LH paved the way for the final isolation of LHRH. Doctor Roger Guillemin and his group (Max Amoss, Roger Burgess, Catherine Rivers, Wylie Vale, Richard Blackwell, and Thomas Dunn), who had recently moved en masse to the Salk Institute, chemically synthesized LH-RH at almost the same time as Schally's group in New Orleans. The race to isolate this intriguing brain peptide was obviously a photo finish. Dr. Andrew Schally and Roger Guillemin received the Nobel prize in 1977 for the synthesis of LH-RH. The clinical studies of this compound were carried out by Arturo Zarate of Mexico City in collaboration Schally and other investigators around the world. Since 1971 Dr. Schally and his group at the Veterans Hospital at Tulane have been actively involved in the development of LH-RH antagonists. One of these antagonists, Cetrorelix (SB-75) (ASTA Medica, Frankfurt am Main, Germany) appears to have many uses, but is especially valuable to prevent premature LH surges when used in the context of an IVF-ET
Vol. 64, No.2, August 1995
program. There is also some interesting evidence to suggest that this antagonist may have a suppressive effect upon the growth of epithelial ovarian cancers and endometrial malignancies. The antagonists developed by Dr. Schally appear to be both potent and long-acting. All of these contributions and many more give clear evidence of Andrew Schally's unique contributions to the reproductive sciences. Similarly, Dr. Sam McCann can now be classified as one of the pioneers in neuroendocrinology and was responsible for elucidating a considerable amount of the physiology of GnRH release prior to the actual synthesis of LH-RH. It is remarkable to think that next year will be the 25th anniversary of the isolation and synthesis of LH-RH. The isolation and synthesis of LH-RH has made it possible to synthesize large quantities of the decapeptide, agonists, and now antagonists for clinical use. Dr. Schally's peptide laboratory at the VA Hospital in Tulane is still a remarkable beehive of activity. It is inconspicuously located in a series of quonset huts off the Tulane campus, but it has been one of the most productive neuroendocrine laboratories in the world. Like many great scientists Doctor Schally is somewhat of a maverick, and even irreverent at times. In fact his critical energy and the stringency of his scientific thought can quickly exhaust the less endowed. His contributions to science and indirectly to the care of women certainly give him the poetic license privilege to call LH-RH anything that he deems appropriate. Paul G. McDonough, M.D., Editor, Letters Addendum
For additional related correspondence from Dr. Schally and associates see the July issue of Fertility and Sterility CSchally AV, Halmos G, Pinski J. Terminology for Luteinizing Hormone-Releasing Hormone Antagonists. [Letter] Fertil Steril 1995;64: 226.)
Letters-to-the-editor
453
!,
FERTILITY AND STERILITY Copyright
0
1995 American Society for Reproductive Medicine
The Privileges of a Nobel Laureate
To the Editor: A recent letter (1) cites the misuse ofthe terminology ofluteinizing hormone-releasing hormone (LHRH) antagonists and a confusion in the scientific literature. We feel that this is caused not by the issues whether LH-RH receptors are "down-regulated" or not by the LH-RH antagonists, but by the problems with the nomenclature for the hypothalamic hormone that causes the liberation of both LH and FSH from the anterior pituitary gland. These problems about the nomenclature ofLH-RH are becoming more and more acute. Because one of us (S.M.M.e.) discovered LH-RH (2) and the other (A.V.S.) led a team that isolated LH-RH in pure state, determined its structure, synthesized it, and carried out original physiological and collaborative clinical studies (3, 4), we believe that we should be allowed to express our views about the nomenclature of LH-RH and the use of the abbreviation GnRH. Having worked not only on LH-RH, but also on somatostatin and growth hormone-releasing hormone (GH-RH) and their analogues, we recommend the use of the abbreviation LH-RH for luteinizing hormone-releasing hormone and GH-RH for growth hormone-releasing hormone. This recommendation was already made in various reviews (5). It is now well known that LH-RH releases FSH in addition to LH, as it was first shown in 1971 (3). One of us (A.V.S.) was, in fact, the first to propose the name gonadotropin-releasing hormone, abbreviated as GnRH in 1971 (3), but much confusion is caused by this abbreviation. Moreover, the secretion of LH and FSH under acute conditions can be dissociated, so that there can be another FSH-RH (6). Growth hormone (GH) is already used in IVF-ET (Assisted Reproductive Technology) methods and agonistic analogues of GHRH may be used soon (6). The abbreviation GnRH is creating confusion not only when speaking, but also in writing and might even lead to accidents. Recently, FDA sent a memorandum meaning LHRH or GnRH, but they wrote GH-RH. In addition, there are already antagonists of GH-RH (6). As a matter of fact, we warned 22 years ago, that the abbreviation GnRH for gonadotropin-releasing hormone will be confusing, because it is too similar to GH-RH (5). In conclusion, because LH-RH agonists and antag452
Letters-to-the-editor
Printed on acid·free paper in U. S. A.
onists are increasingly used in gynecology and oncology, we recommend that the abbreviation GnRH should be discontinued, at least for the analogues, and LH-RH be used instead.
Andrew V. Schally, Ph.D., M.Dhc. Endocrine, Polypeptide, and Cancer Institute VA Medical Center and Department of Medicine Tulane University School of Medicine New Orleans, Louisiana Samuel M. (Don) McCann, M.D. Department of Physiology University of Texas Southwestern Medical Center Dallas, Texas January 11, 1995 REFERENCES 1. Gordon K. Terminology for GnRH antagonists. Fertil Steril 1994;61:994-5. 2. McCann SM, Taleisnik S, Friedman HN. LH releasing activity in hypothalamic extracts. Proc Soc Exp BioI Med 1960; 104:432-4. 3. Schally AV, Arimura A, Kastin AJ, Matsuo H, Baba Y, Redding TW, et al. The gonadotropin-releasing hormone: one polypeptide regulates the secretion ofluteinizing and follicle stimulating hormones. Science 1971; 173:1036-8. 4. Schally AV, Kastin AJ, Arimura A Hypothalamic folliclestimulating hormone (FSH) and luteinizing hormone (LH)regulating hormone: structure, physiology and clinical studies. Fertil Steril 1971;22:703-21. 5. Schally AV, Kastin AJ, Arimura A FSH-releasing hormone and LH-releasing hormone. Vitamins Hormones 1972;30:83164.
Note. Additional other references available upon request.
The author elected not to respond. Paul G. McDonough, M.D., Editor, Letters Editorial Comment The Privileges of a Nobel Laureate
Among the privileges of a Nobel laureate is the right to suggest a proper name or at least an operational name for a substance that one has isolated. The original isolation of luteinizing hormone-releasing hormone (LH-RH) by Andrew Schally required 160,000 porcine hypothalami in order to produce just 250 micrograms of the putative substance. ConsiderFertility and Sterility
ing the limited analytical methods available at the time it is remarkable that the structure of LH-RH was deduced from this small amount of starting material. The final structural analysis and the synthesis of the candidate peptide from this starting material was accomplished by a remarkable Japanese chemist working with Schally by the name of Hisayuki Matsuo. Akira Arimura, a physiologist, was responsible for verifying the biological activity of the newly synthesized LH-RH. Today his task may seem like "a piece of cake," but in 1971 the only available techniques to quantitate the LH and FSH response to the final test material provided by Matsuo were bioassays. These gonadotropin bioassays were difficult, problematic, and plagued with inconsistent results. It was a "twist of fate" that brought Gordon Niswender to his rescue. Doctor Niswender developed and provided to Doctor Arimura the first rabbit antiovine LH antibodies. These antibodies cross-reacted with LH from all mammalian species and were provided by Doctor Niswender under the by line of serum #15. The development of a reliable solid-phase RIA for LH paved the way for the final isolation of LHRH. Doctor Roger Guillemin and his group (Max Amoss, Roger Burgess, Catherine Rivers, Wylie Vale, Richard Blackwell, and Thomas Dunn), who had recently moved en masse to the Salk Institute, chemically synthesized LH-RH at almost the same time as Schally's group in New Orleans. The race to isolate this intriguing brain peptide was obviously a photo finish. Dr. Andrew Schally and Roger Guillemin received the Nobel prize in 1977 for the synthesis of LH-RH. The clinical studies of this compound were carried out by Arturo Zarate of Mexico City in collaboration Schally and other investigators around the world. Since 1971 Dr. Schally and his group at the Veterans Hospital at Tulane have been actively involved in the development of LH-RH antagonists. One of these antagonists, Cetrorelix (SB-75) (ASTA Medica, Frankfurt am Main, Germany) appears to have many uses, but is especially valuable to prevent premature LH surges when used in the context of an IVF-ET
Vol. 64, No.2, August 1995
program. There is also some interesting evidence to suggest that this antagonist may have a suppressive effect upon the growth of epithelial ovarian cancers and endometrial malignancies. The antagonists developed by Dr. Schally appear to be both potent and long-acting. All of these contributions and many more give clear evidence of Andrew Schally's unique contributions to the reproductive sciences. Similarly, Dr. Sam McCann can now be classified as one of the pioneers in neuroendocrinology and was responsible for elucidating a considerable amount of the physiology of GnRH release prior to the actual synthesis of LH-RH. It is remarkable to think that next year will be the 25th anniversary of the isolation and synthesis of LH-RH. The isolation and synthesis of LH-RH has made it possible to synthesize large quantities of the decapeptide, agonists, and now antagonists for clinical use. Dr. Schally's peptide laboratory at the VA Hospital in Tulane is still a remarkable beehive of activity. It is inconspicuously located in a series of quonset huts off the Tulane campus, but it has been one of the most productive neuroendocrine laboratories in the world. Like many great scientists Doctor Schally is somewhat of a maverick, and even irreverent at times. In fact his critical energy and the stringency of his scientific thought can quickly exhaust the less endowed. His contributions to science and indirectly to the care of women certainly give him the poetic license privilege to call LH-RH anything that he deems appropriate. Paul G. McDonough, M.D., Editor, Letters Addendum
For additional related correspondence from Dr. Schally and associates see the July issue of Fertility and Sterility CSchally AV, Halmos G, Pinski J. Terminology for Luteinizing Hormone-Releasing Hormone Antagonists. [Letter] Fertil Steril 1995;64: 226.)
Letters-to-the-editor
453
!,