Molecular and structural basis of androgen receptor responses to dihydrotestosterone, medroxyprogesterone acetate and Δ4-tibolone

Bianco‐Miotto, Tina; Trotta, Andrew P.; Need, Eleanor F.; Lee, Alice M. C.; Ochnik, Aleksandra M.; Giorgio, Lauren; Leach, Damien A.; Swinstead, Erin E.; O’Loughlin, Melissa A.; Newman, Michelle R.; Birrell, Stephen N.; Butler, Lisa M.; Harris, Jonathan M.; Buchanan, Grant

doi:10.1016/j.mce.2013.11.002

Cited by 2 publications

(1 citation statement)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MPA has been described as an AR-agonist harboring either androgenic or anti-androgenic effects, dependent on dose and context. MPA binds with a similar affinity to AR as the native ligand 5alfadihydrotestosterone and can disrupt AR signaling [ 19 – 21 ]. However, while a role for the AR in colorectal cancer has been proposed [ 22 ], we have previously shown that the AR is not expressed in colonic epithelial cells [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Colorectal tumor prevention by the progestin medroxyprogesterone acetate is critically dependent on postmenopausal status

et al. 2018

View full text Add to dashboard Cite

The large randomized placebo controlled trials of the Women’s Health Initiative have shown that the combination of estrogen and progestin medroxyprogesterone acetate (MPA) protects from colorectal cancer in postmenopausal women. No effect was observed in women treated with estrogen alone. This suggests that progesterone, or more specifically the progestin MPA may have chemopreventive activity. The effect of MPA on colorectal carcinogenesis has been difficult to study in animal models. Most models are not affected by either depleting female hormones by ovariectomy or treatment with MPA. Importantly, an ovariectomy fails to reproduce one of the hall marks of the postmenopausal state in women with intact ovaries. That is, the continued production of androgens by the atrophic postmenopausal ovaries. Here we show that adenoma incidence is increased in the vinyl cylcohexene diepoxide (VCD) mouse model of the menopause compared to age matched fertile female mice. Treatment with MPA protected VCD treated mice from adenomagenesis, but had no effect on adenoma numbers in age-matched fertile female mice. Our data show that the protective effect of MPA depends on the postmenopausal state and suggest that MPA monotherapy may be studied as a chemopreventive agent in postmenopausal women.

show abstract