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Inhibiting 3βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer

Zemin Hou1, Shengsong Huang2, Zejie Mei1

  • 1State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.

Cell Reports. Medicine
|May 2, 2022
PubMed

Insights

Prostate cancer progression is linked to progesterone, not just androgens. Inhibiting progesterone production may offer new therapeutic strategies for patients, as elevated levels indicate poor outcomes.

Area of Science:

  • Endocrinology
  • Oncology
  • Metabolomics

Background:

  • Prostate cancer growth is typically linked to androgens.
  • The progression of prostate cancer after androgen deprivation suggests other contributing factors, termed oncometabolites.
  • The role of progesterone in prostate cancer has not been fully elucidated.

Purpose of the Study:

  • To investigate the potential oncogenic effects of progesterone in prostate cancer.
  • To identify therapeutic strategies targeting progesterone production or action.

Main Methods:

  • Mass-spectrometry-based screening of clinical specimens.
  • Retrospective analysis of clinical data from prostate cancer patients.
  • Investigated the effects of progesterone on androgen receptor (AR) target genes and cell proliferation via GATA2.

Main Results:

  • Progesterone, at high doses, activates both canonical and non-canonical AR target genes.
  • Physiological levels of progesterone promote cell proliferation through GATA2.
  • Inhibitors of 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) were found to suppress progesterone generation.
  • Increased progesterone levels correlate with poorer clinical outcomes and may serve as a predictive biomarker.

Conclusions:

  • Progesterone acts as an oncogenic hormone in prostate cancer.
  • Targeting progesterone generation or its effects presents a potential therapeutic avenue for prostate cancer patients.
  • Progesterone may be a useful predictive biomarker for prostate cancer prognosis.
Keywords:
3βHSD1GATA2abirateronebiochanin Adrug resistanceoncometabolitepredictive biomarkerprogesteroneprostate cancer

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