Receptor-binding affinity of gonadotropin-releasing hormone analogs: analysis by radioligand-receptor assay.

A recently developed radioligand-receptor assay for pituitary gonadotropin-releasing hormone (GnRH) receptors, employing a radioiodinated superagonist analog as the ligand, was used to analyze the receptor-binding properties of several GnRH analogs. This receptor assay is specific for GnRH and related peptides with agonist or antagonist activity. All superagonist analogs had equilibrium association constants (Ka) between 4- and 8-fold greater than that of the natural GnRH decapeptide (Ka = 6.6 × 108 m−1). Conversely, weak agonists and inactive analogs were bound with affinities 0.003–0.05 times that of GnRH. Weak antagonists, such as [D-Phe2]GnRH and [DPhe2, D-Phe6]GnRH, had lower binding constants, while the most potent antagonist, [D-pGlu1, D-Phe2, D-Trp3,6]GnRH, exhibited 8-fold higher affinity than GnRH for pituitary receptors. There was a general positive correlation between receptor-binding affinity and relative biological activity, whether agonist or antagonist, for the several GnRH analogs tested....

[1]  D. Rodbard,et al.  Radioiodinated nondegradable gonadotropin-releasing hormone analogs: new probes for the investigation of pituitary gonadotropin-releasing hormone receptors. , 1979, Endocrinology.

[2]  K. Catt,et al.  Angiotensin II receptors in adrenal cortex and uterus. Binding and activation properties of angiotensin analogues. , 1979, The Journal of biological chemistry.

[3]  R. Clayton,et al.  Luteinizing hormone-releasing hormone inactivation by purified pituitary plasma membranes: effects of receptor-binding studies. , 1979, Endocrinology.

[4]  A. Schally,et al.  Cyclic analogues of luteinizing hormone-releasing hormone with significant biological activities. , 1978, Journal of medicinal chemistry.

[5]  W. Vale,et al.  [D-pGlu1,D-Phe2,D-Trp3,6]-LRF. A potent luteinizing hormone releasing factor antagonist in vitro and inhibitor of ovulation in the rat. , 1978, Life sciences.

[6]  D. Rodbard,et al.  Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. , 1978, The American journal of physiology.

[7]  C. Bergquist,et al.  Inhibition of ovulation in women by chronic treatment with a stimulatory LRH analogue--a new approach to birth control? , 1978, Contraception.

[8]  D. Heber,et al.  Pituitary receptor binding activity of active, inactive, superactive and inhibitory analogs of gonadotropin-releasing hormone. , 1978, Biochemical and biophysical research communications.

[9]  C. Beattie,et al.  The anti-reproductive pharmacology of LH-RH and agonistic analogues. , 1978, International journal of fertility.

[10]  A. Schally,et al.  Binding capacity of luteinizing hormone-releasing hormone and its analogues for pituitary receptor sites. , 1977, Biochemical and biophysical research communications.

[11]  A. Schally,et al.  Uptake of iodinated luteinizing hormone releasing hormone analogs in the pituitary. , 1977, Endocrinology.

[12]  J. Marshall,et al.  LHRH‐PITUITARY PLASMA MEMBRANE BINDING: THE PRESENCE OF SPECIFIC BINDING SITES IN OTHER TISSUES , 1976, Clinical endocrinology.

[13]  A. Schally,et al.  Antagonistic activity of analogs of luteinizing hormone-releasing hormone (LH-RH) in vitro , 1976, Molecular and Cellular Endocrinology.

[14]  W. White,et al.  Delay of puberty and inhibition of reproductive processes in the rat by a gonadotropin-releasing hormone agonist analog. , 1976, Fertility and sterility.

[15]  A. Schally,et al.  Blockade of ovulation in rats by inhibitory analogs of luteinizing hormone-releasing hormone , 1976 .

[16]  Momany Fa,et al.  Conformational energy analysis of the molecule, luteinizing hormone-releasing hormone. I. Native decapeptide. , 1976 .

[17]  F. Momany.  Conformational energy analysis of the molecule, luteinizing hormone-releasing hormone. 2. Tetrapeptide and decapeptide analogues. , 1976, Journal of the American Chemical Society.

[18]  A. Schally,et al.  Analogs of luteinizing hormone-releasing hormone with increased biological activity produced by D-amino acid substitutions in position 6. , 1976, Journal of medicinal chemistry.

[19]  A. Schally,et al.  Inhibition of luteinizing hormone release by analogs of luteinizing hormone-releasing hormone (LHRH) in vitro. , 1976, Endocrinology.

[20]  N. Ling,et al.  PHARMACOLOGY OF HYPOTHALAMIC REGULATORY PEPTIDES , 1976, Clinical endocrinology.

[21]  A. Kastin,et al.  Edward T. Tyler Prize Oration: LH-releasing hormone and its analogues: recent basic and clinical investigations. , 1976, International journal of fertility.

[22]  V. Garsky,et al.  Luteinizing hormone-releasing hormone. Antiovulatory activity of analogs substituted in positions 2 and 6. , 1975, Journal of medicinal chemistry.

[23]  A. Schally,et al.  LH-releasing activity of potent LH-RH analogs in vitro. , 1975, Biochemical and Biophysical Research Communications - BBRC.

[24]  J. Marshall,et al.  Preparation of Biologically Active 125I LH-RH Suitable for Membrane-Binding Studies , 1975 .

[25]  A. Corbin,et al.  Inhibition of the pre-ovulatory proestrous gonadotropin surge, ovulation and pregnancy with a peptide analogue of luteinizing hormone releasing hormone , 1975 .

[26]  A. Schally,et al.  Stereoisomers of luteinizing hormone-releasing hormone. , 1974, Biochemical and biophysical research communications.

[27]  W. Vale,et al.  Synthetic analogs of the hypothalamic luteinizing hormone releasing factor with increased agonist or antagonist properties. , 1973, Biochemistry.

[28]  D Rodbard,et al.  Computer analysis of radioligand assay and radioimmunoassay data. , 1970, Acta endocrinologica. Supplementum.