Abstract
The basic assumption in developing competitive inhibitors of luteinizing hormone/follicle stimulating hormone-releasing hormone (LH/FSH-RH), the structure of which is shown in Figure 1, was that analogs could be designed which could retain the ability to bind to pituitary receptor sites whilst being devoid of gonadotropin-releasing activity. The first indication that this approach was valid came out of work by Vale et al. (1972) who found that removal of histidine from the peptide chain gave a nonapeptide of very low LH-RH activity which was capable of inhibiting the action of LH-RH on cultures of anterior pituitary cells. This inhibition was, however, weak and subsequently could not be demonstrated in vivo in rats (Vilchez-Martinez et al., 1974a). Other inhibitors based on the original decapeptide sequence were shown (Vilchez-Martinez et al., 1974a) to be active in vivo; however, these were also too weak to be of practical value. It became obvious, therefore, that ways must be found to substantially raise the binding affinity of an inhibitor, again without increasing agonistic activity to any great extent.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Arimura, A., Vilchez-Martinez, J.A., Coy, D.H., Coy, E.J., Hirotsu, Y., and Schally, A.V. (1974) Endocrinology 95, 1174–1177.
Corbin, A., and Beattie, C.W. (1975) Endocrine Res. Commun. 2, 1–23.
Coy, D.H., Coy, E.J., Schally, A.V., Vilchez-Martinez, J.A., Debeljuk, L., Carter, W.H., and Arimura, A. (1974a) Biochemistry 13, 323–326.
Coy, D.H., Coy, E.J., Schally, A.V., Vilchez-Martinez, J.A., Hirotsu, Y., and Arimura, A (1974b) Biochem. Biophys. Res. Commun. 57, 335–340.
Coy, D.H., Vilchez-Martinez, J.A., Coy, E.J., Arimura, A., and Schally, A.V. (1976), J. Med. Chem., in press.
Coy, D.H., Vilchez-Martinez, J.A., Coy, E.J., Nishi, N., Arimura, A., and Schally, A.V. (1975) Biochemistry 14, 1848–1851.
de la Cruz, A., Arimura, A., and Schally, A.V. (1976a) Endocrinology, in press.
de la Cruz, A., Coy, D.H., Schally, A.V., Coy, E.J., de la Cruz, K.G., and Arimura, A. (1975) Proc.Soc.Exp.Biol.Med. 149, 576–579.
de la Cruz, A., Coy, D.H., Vilchez-Martinez, A.J., Arimura, A., and Schally, A.V. (1976), Science, in press.
Foell, T.J. and Yardley, J.P. (1974) U.S. Patent 3,855,199.
Fujino, M., Fukuda, T., Shinagawa, S., Kobayashi, S., Yamakazi, I., Nakagama, R., Seely, J.H., White, W.F., Rippel, R.H. (1974a) Biochem.Biophys. Res.Commun. 60, 406–413.
Fujino, M., Kobayashi, S., Obayashi, M., Shinagawa, S., Fukuda, T., Kitada, C., Nakagawa, R., Yamakazi, I., White, W.F., and Rippel, R.H. (1972) Biochem.Biophys.Res.Commun. 49, 863–869.
Fujino, M., Yamakazi, S., Kobayashi, S., Fukuda, T., Shinagawa, S., Nakayama, R., White, W.F., and Rippel, R.H. (1974) Biochem. Biophys. Res. Commun. 57, 1248–1256.
Monahan, M., Amoss, M.S., Anderson, H.A., and Vale, W. (1973), Biochemistry 12, 4616–4620.
Rees, R.W.A., Foell, T.J., Chai, S.Y., and Grant, N. (1974) J.Med. Chem..17, 1016–1019.
Vale, W., Grant, G., Rivier, J., Monahan, M., Amoss, M., Blackwell, R., Burgus, R., and Guillemin, R. (1972). Science 176, 933–934.
Vilchez-Martinez, J.A., Coy, D.H., Arimura, A., Coy, E.J., Hirtosu, Y., and Schally, A.V. (1974c) Biochem.Biophys.Res.Commun. 59, 1226–1232.
Vilchez-Martinez, J.A., Coy, D.H., Coy, E.J., Arimura, A., and Schally, A.V. (1976) Endocrinology, in press.
Vilchez-Martinez, J.A., Coy, D.H., Coy, E.J., Schally, A.V., and Arimura, A. (1975) Fert.Ster. 26, 554–559.
Vilchez-Martinez, J.A., Schally, A.V., Coy, D.H., Coy, E.J., Debeljuk, L., and Arimura, A. (1974b) Endocrinology 95, 213–218.
Vilchez-Martinez, J.A., Schally, A.V., Debeljuk, L., Coy, D.H., Coy, E.J., Arimura, A., and Yanaihara, N. (1974a) Neuroendocrinol. 14, 121–128.
Zeballos, G. and McCann, S.M. (1975) Endocrinology 96, 1377–1385.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1976 Plenum Press, New York
About this chapter
Cite this chapter
Coy, D.H., Coy, E.J., Vilchez-Martinez, J.A., de la Cruz, A., Arimura, A., Schally, A.V. (1976). Suppression of Gonadotropin Release and Ovulation in Animals by Inhibitory Analogs of Luteinizing Hormone-Releasing Hormone. In: Labrie, F., Meites, J., Pelletier, G. (eds) Hypothalamus and Endocrine Functions. Current topics in Molecular Endocrinology, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-2598-7_18
Download citation
DOI: https://doi.org/10.1007/978-1-4684-2598-7_18
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-2600-7
Online ISBN: 978-1-4684-2598-7
eBook Packages: Springer Book Archive