Abstract: The present invention is directed to the neutralizing prolactin receptor antibody 006-H08, as well as maturated forms thereof, and antigen-binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

Abstract: The present invention is directed to the neutralizing prolactin receptor antibody 005-C04, as well as maturated forms thereof, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

Abstract: The present invention is directed to the neutralizing prolactin receptor antibody 006-H08, as well as maturated forms thereof, and antigen-binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

Abstract: The present invention is directed to the neutralizing prolactin receptor antibody 002-H06, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

Abstract: The present invention is directed to the neutralizing prolactin receptor antibody 005-C04, as well as maturated forms thereof, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

Abstract: The present invention is directed to the neutralizing prolactin receptor antibody 006-H07, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

Abstract: The present invention is directed to pharmaceutical compositions containing one or more neutralizing prolactin receptor antibodies and antigen binding fragments, and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The composition of the invention blocks prolactin receptor-mediated signaling.

Abstract: The present invention is directed to the neutralizing prolactin receptor antibody 002-H08, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

Abstract: Novel co-modulator proteins, designated ARAP3 polypeptides, for nuclear receptors, especially the androgen receptor, are described, which are useful in methods of detecting and treating steroid hormone-dependent diseases that are due to a deficiency of these co-modulator proteins. By measuring the levels of ARAP3 polypeptide expression in tissue samples from an individual a steroid hormone-dependent disease, such as breast cancer, can be detected. The levels of ARAP3 polypeptide expression in the tissue samples can be measured by immunohistochemistry methods, by ELISA methods, by radioimmuno tests, by Northern blot techniques, or by Western blot techniques A method of treating steroid hormone-dependent diseases due to a deficiency of an ARAP3 co-modulator protein in various tissues of an individual includes incorporating ARAP3 co-modulator protein in the tissues using a vector.

Abstract: In the method of determining hormonal effects of substances, a test substance is contacted with Ewing sarcoma protein (EWS) or a derivative of it and with an androgen receptor (NR) or a derivative of it; and the effect of the test substance on binding of EWS with the androgen receptor or its derivative or on ligand-induced activity of the androgen receptor is determined, preferably in a cellular system. A method for determining interference in the co-modulator mechanism between androgen receptor and EWS, which includes measurement of androgen receptor and EWS concentrations, is described. A method for identification and characterization of substances that influence the activity of a nuclear receptor, especially androgen receptor, using EWS or a derivative of it is disclosed.

Abstract: A method for in vitro screening a group of test substances for a ligand using two assay systems, i.e. a cellular or tissue assay system and an enzymatic assay system, is described. First, those test substances are selected which have transcriptional ER-mediated activity measured by an ER-driven reporter gene in the cellular or tissue assay system with an EC50(ER)(half-maximally effective ligand concentration) lower than or equal to 10 nmol/l. Then in an enzymatic assay system the selected test substances having the required transcriptional ER-mediated activity are tested by measuring a physical-chemical interaction (recruitment) of SRC-1 and the ER in the presence of the test substances. The selected ligand activates the ER and induces interaction with the co-present SRC-1 with an E50(ER+SRC) higher than or equal to 100 nmol/l.

Abstract: The method for testing of substances for hormonal effects, especially for androgenic or anti-androgenic effects, includes exposing cells transfected with two vectors to the substances, wherein one vector contains a DNA, which codes for a nuclear receptor protein, or a fragment thereof, especially a human nuclear receptor protein, or a fragment thereof, and the other vector contains a DNA, which codes for the HSRNAAM co-modulator, or a fragment thereof; and measuring transcription activity, which the nuclear receptor protein, or its fragment, activates or releases in the presence of the HSRNAAM co-modulator, or its fragment, and/or measuring the influence of the substance on the interaction between the nuclear receptor protein, or its fragment, and the HSRNAAM co-modulator, or its fragment, by protein-protein interaction or by protein-protein-DNA interaction. Also a method for determining interference in the co-modulation mechanism between androgen receptor protein and HSRNAAM co-modulator is described.

Abstract: In the method of determining hormonal effects of substances, a test substance is contacted with Ewing sarcoma protein (EWS) or a derivative of it and with a nuclear receptor (NR) or a derivative of it; and the effect of the test substance on binding of EWS with the nuclear receptor or its derivative or on ligand-induced activity of the nuclear receptor is determined, preferably in a cellular system. A method for determining interference in the co-modulator mechanism between androgen receptor and EWS, which includes measurement of androgen receptor and EWS concentrations, is described. A method for identification and characterization of substances that influence the activity of a nuclear receptor, especially androgen receptor, using EWS or a derivative of it is disclosed.

Abstract: The method for testing of substances for hormonal effects, especially for androgenic or anti-androgenic effects, includes exposing cells transfected with two vectors to the substances, wherein one vector contains a DNA, which codes for a nuclear receptor protein, or a fragment thereof, especially a human nuclear receptor protein, or a fragment thereof, and the other vector contains a DNA, which codes for the FOXG1C co-modulator, or a fragment thereof; and measuring transcription activity, which the nuclear receptor protein, or its fragment, activates or releases in the presence of the FOXG1C co-modulator, or its fragment, and/or measuring the influence of the substance on the interaction between the nuclear receptor protein, or its fragment, and the FOXG1C co-modulator, or its fragment, by protein-protein interaction or protein-protein-DNA interaction. Further a method for determining interference in the co-modulation mechanism between androgen receptor protein and FOXG1C co-modulator is described.

Abstract: The method for testing of substances for hormonal effects, especially for androgenic or anti-androgenic effects, includes exposing cells transfected with two vectors to the substances, wherein one vector contains a DNA, which codes for a nuclear receptor protein, or a fragment thereof, especially a human nuclear receptor protein, or a fragment thereof, and the other vector contains a DNA, which codes for the HSRNAAM co-modulator, or a fragment thereof; and measuring transcription activity, which the nuclear receptor protein, or its fragment, activates or releases in the presence of the HSRNAAM co-modulator, or its fragment, and/or measuring the influence of the substance on the interaction between the nuclear receptor protein, or its fragment, and the HSRNAAM co-modulator, or its fragment, by protein-protein interaction or by protein-protein-DNA interaction. Also a method for determining interference in the co-modulation mechanism between androgen receptor protein and HSRNAAM co-modulator is described.

Abstract: A method for testing the hormonal effect, especially the androgenic or antiandrogenic effect, of substances is described, in which (a) cells which are transfected with two vectors, one of these vectors containing DNA which codes for a nuclear receptor protein or a fragment thereof, whereas the other vector contains DNA which codes for a co-modulator or a fragment thereof, are exposed to the substance; and (b) the transcription activity which the nuclear receptor or its fragment induces in the presence of the co-modulator or its fragment and/or the effect of the substance on the interaction between the receptor or its fragment and the co-modulator or its fragment is measured by the protein-protein interaction or the protein-protein-DNA interaction. In addition, a method for determining defects in the co-modulation mechanism and means suitable for performing this method are provided.

Abstract: A method of an in vitro screening for a ligand using two assay systems i.e. in a first cellular or tissue assay system, selecting the ligand with transcriptional ER-mediated activity measured by an ER-driven reporter gene, whereby in the first assay system the ligand activates the potency with an EC50(ER) (half-maximally effective ligand concentration) lower than to 10 nmol/l, and, in a second enzymatic assay system, selecting the physical-chemical interaction (recruitment) of SRC-1, wherein the ligand activates the ER and induces interaction with the co-present SRC-1 with an EC50(ER+SRC) higher than to 100 nmol/l.

Abstract: A testing system for identifying effectors of polypeptides (ARAP3 variants) having the respective amino acid sequences represented in Seq. ID Nos. 14 to 18 and 20. In this test system a reporter gene is expressed in a cell transfected with a nucleic acid or in a cell transfected with a vector containing at least one copy of this nucleic acid; the cell, if it contains no nuclear receptor or only a small amount thereof, is also transfected with a vector containing DNA of the nuclear receptor; the cell is cultured in the presence of a plurality of test substances and a change in expression of the reporter gene is measured to find the effectors. The nucleic acid codes one of the polypeptides (ARAP3 variants), or has a nucleotide sequence represented in one of Seq. ID Nos. 1 to 13 and 19, or has a nucleotide sequence hybridized with one of Seq. ID Nos. 1 to 13 and 19 and/or one of the nucleic acid sequences coding polypeptides with an amino acid sequence represented in one of Seq. ID Nos.