Development and potential clinical uses of human prolactin receptor antagonists

被引:165
作者
Goffin, V
Bernichtein, S
Touraine, P
Kelly, PA
机构
[1] Fac Med Necker Enfants Malad, INSERM, U584, F-75730 Paris, France
[2] Univ Paris 05, F-75730 Paris, France
[3] Hop Necker Enfants Malad, Serv Endocrinol & Med Reprod, F-75743 Paris, France
关键词
D O I
10.1210/er.2004-0016
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
There is a large body of literature showing that prolactin (PRL) exerts growth-promoting activities in breast cancer, and possibly in prostate cancer and prostate hyperplasia. In addition, increasing evidence argues for the involvement of locally produced ( autocrine) PRL, perhaps even more than pituitary-secreted ( endocrine) PRL, in tumor growth. Because dopamine analogs are unable to inhibit PRL production in extrapituitary sites, alternative strategies need investigation. To that end, several PRL receptor antagonists have been developed by introducing various mutations into its natural ligands. For all but one of these analogs, the mechanism of action involves a competition with endogenous PRL for receptor binding. Such compounds are thus candidates to counteract the undesired actions of PRL, not only in tumors, but also in dopamine-resistant prolactinomas. In this review, we describe the different versions of antagonists that have been developed, with emphasis on the controversies regarding their characterization, and the limits for their potential development as a drug. The most recently developed antagonist, Delta 1 - 9-G129R-hPRL, is the only one that is totally devoid of residual agonistic activity, meaning it acts as pure antagonist. We discuss to what extent this new molecule could be considered as a lead compound for inhibiting the actions of human PRL in the above-mentioned diseases. We also speculate on the multiple questions that could be addressed with respect to the therapeutic use of PRL receptor antagonists in patients.
引用
收藏
页码:400 / 422
页数:23
相关论文
共 156 条
  • [101] MILLER WL, 1983, ENDOCR REV, V4, P97, DOI 10.1210/edrv-4-2-97
  • [102] The human growth hormone (hGH) antagonist (G120R)hGH does not antagonize GH in the rat, but has paradoxical agonist activity, probably via the prolactin receptor
    Mode, A
    Tollet, P
    Wells, T
    Carmignac, DF
    Clark, RG
    Chen, WY
    Kopchick, JJ
    Robinson, ICAF
    [J]. ENDOCRINOLOGY, 1996, 137 (02) : 447 - 454
  • [103] Dopamine resistance of prolactinomas
    Mark E. Molitch
    [J]. Pituitary, 2003, 6 (1) : 19 - 27
  • [104] Medical management of prolactin-secreting pituitary adenomas
    Molitch M.E.
    [J]. Pituitary, 2002, 5 (2) : 55 - 65
  • [105] HORMONES AND MAMMARY CARCINOGENESIS IN MICE, RATS, AND HUMANS - A UNIFYING HYPOTHESIS
    NANDI, S
    GUZMAN, RC
    YANG, J
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (09) : 3650 - 3657
  • [106] Prolactin regulates mammary epithelial cell proliferation via autocrine/paracrine mechanism
    Naylor, MJ
    Lockefeer, JA
    Horseman, ND
    Ormandy, CJ
    [J]. ENDOCRINE, 2003, 20 (1-2) : 111 - 114
  • [107] Prolactin and prolactin receptors are expressed and functioning in human prostate
    Nevalainen, MT
    Valve, EM
    Ingleton, PM
    Nurmi, M
    Martikainen, PM
    Harkonen, PL
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1997, 99 (04) : 618 - 627
  • [108] Expression and hormone regulation of prolactin receptors in rat dorsal and lateral prostate
    Nevalainen, MT
    Valve, EM
    Ingleton, PM
    Harkonen, PL
    [J]. ENDOCRINOLOGY, 1996, 137 (07) : 3078 - 3088
  • [109] NICOLL CS, 1986, ENDOCR REV, V7, P169, DOI 10.1210/edrv-7-2-169
  • [110] Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer
    Ormandy, CJ
    Hall, RE
    Manning, DL
    Robertson, JFR
    Blamey, RW
    Kelly, PA
    Nicholson, RI
    Sutherland, RL
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1997, 82 (11) : 3692 - 3699