title: [Qualitative and quantitative hormonal regulation in castration-resistant prostate cancer].
abstract: BACKGROUND
  Despite initial sensitivity to androgen deprivation, most metastatic prostate cancer patients will experience recurrence or progression. This evolution, which occurs while seric testosterone level is low, is called castration resistant prostate cancer (CRPC).
  
  
  METHODS
  MEDLINE database was requested for French or English articles published until September 2012 responding to the following keywords: "castration resistant", "prostatic neoplasms", "androgens", "testosterone", "regulat*". Here is a summary of relevant data concerning both qualitative and quantitative hormonal regulation.
  
  
  RESULTS
  androgen blood testing is not related to tissue concentrations, as prostate cancer cells exhibit higher hormones levels. Despite its higher biological efficiency, dihydrotestosterone is not the only mediator of androgen-dependent transcription. Androgen synthesis implies many pathways including lot of alternative ones. Steroïdogenesis can occur out of the testicles and the adrenals, and maybe in tumor cell or tissue. Major and minor androgens levels, as those of co-repressors and activators inside the tumor cell leads to a smooth androgen activity modulation. Many drugs have the ability to block those different steps.
  
  
  CONCLUSIONS
  Castration resistance reflects an androgen activity in tumor cells while major androgen pathway activators are lowered. Alternate pathway include steroids pumps, de novo synthesis by tumor cells or their environment, minor androgens activation by co-factors regulation. Many drugs are known to inhibit those escaping ways. Nowadays they are not efficient enough, because of other minor pathways becoming dominant. Investigations are required but would need new detection techniques of low androgen concentrations in blood as in tissues.
authors: Service d'urologie et transplantation rénale, hôpital Lapeyronie, CHU de Montpellier, 371 avenue du Doyen-Gaston-Giraud, 34295 Montpellier Cedex 5, France. Electronic address: t-murez@chu-montpellier.fr.
authors: T
authors: T
authors: Murez
authors: V
authors: V
authors: Basset
authors: F
authors: F
authors: Audenet
authors: T
authors: T
authors: Lebret
authors: J
authors: J
authors: Branchereau
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens / Q000378:metabolism*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D013196:Dihydrotestosterone / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D013196:Dihydrotestosterone
keywords: Cancer de la prostate; Castration; Hormonal therapy; Hormonothérapie; Prostate cancer; Résistance à la castration; Steroidogenesis; Stéroïdogenèse