+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Regulation of luteinizing hormone-releasing hormone receptor binding by heterologous and autologous receptor-stimulated tyrosine phosphorylation



Regulation of luteinizing hormone-releasing hormone receptor binding by heterologous and autologous receptor-stimulated tyrosine phosphorylation



Proceedings of the National Academy of Sciences of the United States of America 88(6): 2244-2248



Pancreatic cancers overexpress tyrosine kinase and luteinizing hormone-releasing hormone (LH-RH) receptor (LH-RHR)-mediated tyrosine phosphatase. LH-RHR is a 60-kDa protein. One of the substrates of epidermal growth factor (EGF)-stimulated tyrosine kinase activity and LH-RH- and somatostatin-stimulated tyrosine phosphatase activity is also a 60-kDa protein. This suggests the possibility that LH-RHR regulation by tyrosine phosphatase and tyrosine kinase is mediated by (de)phosphorylation of existing LH-RHR. To test this hypothesis, membranes of MIA PaCa-2 cells, a human dedifferentiated pancreatic cancer cell line, were incubated without hormone (control) or with 0.1 microM EGF or somatostatin analogue RC-160 for 1 hr at 4 degrees C to phosphorylate the 60-kDa protein. Competition binding experiments with I125-labeled [D-Trp6]LH-RH by displacement with a nonradioactive ligand showed that the LH-RH binding in 69% of the points was increased by EGF and 85% was decreased by RC-160 compared with controls (n = 61; both significant, P less than 0.001). The specific binding was altered, increasing 50-150% after preincubation with EGF and decreasing 60-70% after RC-160. No change was seen in the binding affinity constant after pretreatment with EGF or RC-160. This shows that phosphorylation regulates binding of LH-RH and may explain the up-regulation by EGF and down-regulation by RC-160 and by LH-RH of the LH-RH response.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 018090289

Download citation: RISBibTeXText

PMID: 1672452

DOI: 10.1073/pnas.88.6.2244


Related references

Synthesis, luteinizing hormone-releasing activity, and receptor binding of chicken hypothalamic luteinizing hormone-releasing hormone. Endocrinology 113(4): 1364-1369, 1983

Down regulation of testicular androgen biosynthesis and luteinizing hormone receptor levels by a luteinizing hormone releasing hormone agonist role of prolactin. Clinical Research 26(6): 839A, 1978

Clinical treatment of infertility using luteinizing hormone releasing hormone analogs studies of luteinizing hormone receptor regulation. Clinical Chemistry 26(7): 1020, 1980

Inhibition of ovarian receptor levels and function by treatment with luteinizing hormone releasing hormone or its agonists in the rat and possible luteolytic effects of luteinizing hormone releasing hormone in normal women. Tolis, G Et Al (Ed ) Clinical Neuroendocrinology: A Pathophysiological Approach Xviii+474p Raven Press: New York, N Y , Usa Illus P115-128, 1979

Effect of pre incubation with different concentrations of luteinizing hormone releasing hormone on subsequent luteinizing hormone release caused by supramaximally active amounts of luteinizing hormone releasing hormone role of luteinizing hormone releasing hormone induced protein synthesis. Life Sciences 21(11): 1621-1628, 1977

Luteinizing hormone receptor binding inhibitor an inhibitor of in vitro luteinizing hormone binding to ovarian receptors and luteinizing hormone stimulated progesterone synthesis by ovary. Spilman, Charles H And John W Wilks (Ed ) Novel Aspects Of Reproductive Physiology Proceedings Of The 7th Brook Lodge Workshop on Problems Of Reproductive Physiology Xvi+397p Illus Spectrum Publications, Inc: New York, N Y , Usa; London, England (Dist By Halsted Press/Wiley: New York, N Y , Usa) ISBN 0-89335-050-8; ISBN 0-470-26368-7: 61-80, 1978

In vivo comparison of luteinizing hormone releasing hormone and follicle stimulating hormone releasing hormone activities of de glycine 10 proline 9 ethylamide luteinizing hormone releasing hormone glycine 10 proline 9 propylamide luteinizing hormone releasing hormone and luteinizing hormone releasing hormone using immature male rats. Proceedings of the Society for Experimental Biology & Medicine 146(1): 17-20, 1974

Dynamics of gonadotropin releasing hormone stimulated luteinizing hormone release in vitro as related to the behavior of gonadotropin releasing hormone receptor in solution. Clinical Research 28(2): 271A, 1980

Further Evidence that Most Luteinizing Hormone-Releasing Hormone Neurons are not Directly Estrogen-Responsive: Simultaneous Localization of Luteinizing Hormone-Releasing Hormone and Estrogen Receptor Immunoreactivity in the Guinea-Pig Brain. Journal of Neuroendocrinology 4(3): 311-317, 1992

The metabolic serum clearance of luteinizing hormone releasing hormone as an indicator of the endogenous luteinizing hormone releasing hormone level influence of a chronic treatment with a potent luteinizing hormone releasing hormone analog. Acta Endocrinologica Suppl. (225): 228, 1979

Regulation of luteinizing hormone receptor expression: evidence of translational suppression in vitro by a hormonally regulated mRNA-binding protein and its endogenous association with luteinizing hormone receptor mRNA in the ovary. Journal of Biological Chemistry 280(52): 42809-42816, 2005

Effect of enzymic digestion and specific chemical treatment on antibody binding of luteinizing hormone releasing hormone and a presumptive luteinizing hormone releasing hormone pro hormone. South African Journal of Science 73(11): II, 1977

Involvement of H1 histamine receptor in basal and estrogen-stimulated luteinizing hormone-releasing hormone secretion in rats in vitro. Neuroendocrinology 45(3): 191-196, 1987

Factor c luteinizing hormone inhibitory hormone which inhibits the luteinizing hormone from basal release and from synthetic luteinizing hormone releasing hormone and studies on purification of follicle stimulating hormone releasing hormone. Biochemical & Biophysical Research Communications 63(1): 62-68, 1975

A method to measure the distribution pattern of specific nerve terminals in sampled regions studies on tyrosine hydroxylase luteinizing hormone releasing hormone thyroid stimulating hormone releasing hormone and growth hormone release inhibiting hormone immuno fluorescence. Journal of Histochemistry and Cytochemistry 25(11): 1222-1236, 1977