Adrenocorticotropic hormone is involved in regulation of androgen synthesis in men receiving androgen deprivation therapy for localized prostate cancer

J Urol. 2010 Nov;184(5):1971-6. doi: 10.1016/j.juro.2010.06.115.

Abstract

Purpose: We elucidated the regulatory mechanism of adrenal androgen synthesis and examined the influence of pituitary-adrenal axis activity on prostate specific antigen during androgen deprivation therapy.

Materials and methods: A total of 72 patients with localized prostate cancer were prospectively studied based on blood samples before and after androgen deprivation therapy for 6 months. Serum pituitary hormones, androgens and prostate specific antigen were measured using highly sensitive assays.

Results: After androgen deprivation therapy serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, dehydroepiandrosterone sulfate, androstenedione and prostate specific antigen decreased compared with those at the baseline (all values p <0.001). No difference was noted between serum levels before and after androgen deprivation therapy in growth hormone (p = 0.098) and adrenocorticotropic hormone (p = 0.101). Each serum level of luteinizing hormone, follicle-stimulating hormone and growth hormone after androgen deprivation therapy was not correlated with the serum levels of androgens or prostate specific antigen. The serum adrenocorticotropic hormone level after androgen deprivation therapy was correlated with the serum levels of testosterone (p = 0.002), dehydroepiandrosterone sulfate (p = 0.002), androstenedione (p = 0.006) and prostate specific antigen (p <0.001). Serum dehydroepiandrosterone sulfate and androstenedione levels were also correlated with serum prostate specific antigen (p <0.001 and p = 0.002, respectively).

Conclusions: In patients treated with androgen deprivation therapy the pituitary-adrenal axis mediated by adrenocorticotropic hormone has a central role in the regulation of androgen synthesis. Serum adrenocorticotropic hormone and adrenal androgen concentrations were correlated with the posttreatment prostate specific antigen. Adrenocorticotropic hormone mediated androgen synthesis is a potential target for advanced androgen deprivation therapy.

MeSH terms

  • Adrenocorticotropic Hormone / physiology*
  • Aged
  • Androgen Antagonists / therapeutic use*
  • Androgens / biosynthesis*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Flutamide / therapeutic use*
  • Goserelin / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism*

Substances

  • Androgen Antagonists
  • Androgens
  • Antineoplastic Agents, Hormonal
  • Goserelin
  • Flutamide
  • Adrenocorticotropic Hormone