Presence and characteristics of receptors for [D-Trp⁶]luteinizing hormone releasing hormone and epidermal growth factor in human ovarian cancer

This study was undertaken to establish the presence and characteristics of receptors for [D-Trp⁶]LH-RH on the membranes of human ovarian cancer. Specific binding of [¹²⁵I, D-Trp⁶]LH-RH was found in 29 of 37 (78.4%) ovarian cancers and in 6 of 11 (54.5%) non-malignant human ovaries. Ligand binding was dependent on time and plasma membrane concentration in a fashion expected of a peptide hormone. Saturation, kinetic and displacement data were consistent with the presence of a highly specific, single class of noncooperative binding site. On the basis of receptors affinity, LH-RH-receptor-positive ovarian cancers could be divided into two groups: high affinity group (K(d)=2.71±0.60 nM; B(max)=0.46±0.07 pmol/mg membrane protein) comprising 55% of tumors, and low affinity group (K(d)=78.0±19.6 nM; B(max)=9.44±2.68 pmol/mg membrane protein) which included 45% of tumors. LH-RH antagonist Cetrorelix showed an affinity to LH-RH receptors on ovarian cancers 14 times higher than the agonist [D-Trp⁶]LH-RH. Using ¹²⁵I-epidermal growth factor, specific high affinity receptors were also detected in membranes from 13 of 24 (54%) ovarian cancers and 5 of 11 (45%) non-malignant ovaries. The demonstration of LH-RH receptors in human ovarian cancers provides a rationale for the use of therapeutic approaches based on LH-RH analogues in this malignancy. The probable involvement of growth factors in the development of ovarian cancers suggests the merit of trying a combined therapy based on analogs of LH-RH and somatostatin for this carcinoma.