+ 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

Gonadotropin-releasing hormone (GnRH)-binding sites in human breast cancer cell lines and inhibitory effects of GnRH antagonists

Gonadotropin-releasing hormone (GnRH)-binding sites in human breast cancer cell lines and inhibitory effects of GnRH antagonists

Journal of Clinical Endocrinology and Metabolism 64(3): 425-432

GnRH-binding sites have previously been described in human breast tumors, and a GnRH agonist has been shown to inhibit growth of the MCF-7 human breast cancer cell line. We have investigated the presence of GnRH-binding sites in ZR-75-1, MDA-MB-231, Sk Br 3, MDA-MB-157, and MCF-7 human breast cancer cell lines and the effect of GnRH analogs on the incorporation of [3H]thymidine and 14C-labeled amino acids into DNA and protein. Specific GnRH-binding sites were present in membrane preparations of all five human breast carcinoma cell lines. Studies in three cell lines indicated low affinity (Kd, 1.6-3.0 X 10(-6) M) GnRH binding similar to that reported in human placenta and corpus luteum. In contrast, human pituitary GnRH receptors were of high affinity (Kd, 4.8 X 10(-9) M). Breast carcinoma cell GnRH-binding sites also differed from the pituitary receptor in their inability to discriminate between GnRH and superactive analogs. Binding of a [125I]GnRH analog to ZR-75-1 breast cancer cells and pituitary membranes was affected similarly by various cations. GnRH antagonists rapidly inhibited [3H]thymidine incorporation into DNA (within 3 hr), and this effect was reversible. GnRH antagonists also inhibited cell growth, but only after 6 days. GnRH agonists did not alter either thymidine incorporation or growth. The present observations of low affinity GnRH-binding sites in breast cancer cell lines and inhibitory effects of GnRH antagonists point to the possibility of an autocrine regulatory role of GnRH-like peptides in mammary cells.

Please choose payment method:

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

Accession: 040224832

Download citation: RISBibTeXText

PMID: 3029154

DOI: 10.1210/jcem-64-3-425

Related references

Characterization of gonadotropin releasing hormone gnrh analogue binding sites in human breast cancer. Journal of Cancer Research and Clinical Oncology 116(Suppl. Part 1): 22, 1990

Mutations remote from the human gonadotropin-releasing hormone (GnRH) receptor-binding sites specifically increase binding affinity for GnRH II but not GnRH I: evidence for ligand-selective, receptor-active conformations. Journal of Biological Chemistry 280(33): 29796-29803, 2005

Inhibitory effect of pure 31-kilodalton bovine inhibin on gonadotropin-releasing hormone (GnRH)-induced up-regulation of GnRH binding sites in cultured rat anterior pituitary cells. Endocrinology 124(1): 363-368, 1989

Expression of gonadotropin-releasing hormone II (GnRH-II) receptor in human endometrial and ovarian cancer cells and effects of GnRH-II on tumor cell proliferation. Journal of Clinical Endocrinology and Metabolism 87(3): 1427-1430, 2002

Characterization of a 3H-GnRH method for the measurement of GnRH binding sites in human breast cancer and breast cancer cell lines. International Journal of Oncology 7(2): 371-375, 1995

Regulation of gonadotropin subunit messenger ribonucleic acid expression in gonadotropin-releasing hormone (GnRH)-deficient female rats: effects of GnRH, galanin, GnRH-associated peptide, neuropeptide-Y, and thyrotropin-releasing hormone. Biology of Reproduction 53(1): 1-7, 1995

Expression of gonadotropin-releasing hormone type-I (GnRH-I) and type-II (GnRH-II) in human peripheral blood mononuclear cells (PMBCs) and regulation of B-lymphoblastoid cell proliferation by GnRH-I and GnRH-II. Experimental and Clinical Endocrinology and Diabetes 112(10): 587-594, 2004

Estradiol regulates gonadotropin-releasing hormone (GnRH) and its receptor gene expression and antagonizes the growth inhibitory effects of GnRH in human ovarian surface epithelial and ovarian cancer cells. Endocrinology 142(2): 580-588, 2001

Identification of Phe313 of the gonadotropin-releasing hormone (GnRH) receptor as a site critical for the binding of nonpeptide GnRH antagonists. Molecular Endocrinology 14(5): 671-681, 2000

Gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists do not alter endogenous GnRH secretion in short-term castrated rams. Endocrinology 127(5): 2523-2529, 1990

Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death. Journal of Clinical Endocrinology and Metabolism 90(7): 4287-4298, 2005

Two forms of gonadotropin-releasing hormone (GnRH) are expressed in human breast tissue and overexpressed in breast cancer: a putative mechanism for the antiproliferative effect of GnRH by down-regulation of acidic ribosomal phosphoproteins P1 and P2. Cancer Research 62(4): 1036-1044, 2002

Neuropeptide Y modulates the binding of a gonadotropin-releasing hormone (GnRH) analog to anterior pituitary GnRH receptor sites. Endocrinology 128(5): 2309-2316, 1991

Presence of gonadotropin-releasing hormone (GnRH) binding sites and compounds with GnRH-like activity in the ovary of African catfish, Clarias gariepinus. Biology of Reproduction 50(3): 643-652, 1994