Characterisation of progestins used in hormonal contraception and progesterone via the progesterone receptor

Enfield, Kim; Cartwright, Meghan; Toit, Renate Louw-du; Avenant, Chanel; Africander, Donita; Hapgood, Janet P.

doi:10.1016/j.bbrc.2020.09.058

Cited by 7 publications

(1 citation statement)

References 31 publications

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“…In particular, their differential activities versus the progesterone receptor (PR), androgen receptor (AR), glucocorticoid, and mineralocorticoid receptor have been characterized with reporter assays. A recent side-by-side comparison of various progestins used in OCs revealed cell line-and transfection-related differences (Enfield et al, 2020) pointing to the limited value of such in vitro models for making clinical predictions and the need for better models. Indeed, little is known about the effects of different progestins on the breast epithelium because we lacked adequate models to study hormone action (Ö zdemir et al, 2018;Brisken & Scabia, 2020).…”

Section: Introductionmentioning

confidence: 99%

Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation

et al. 2021

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Hormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progesterone and progestins affect the breast epithelium is poorly understood because we lack adequate models to study this. We hypothesized that individual progestins differentially affect breast epithelial cell proliferation and hence breast cancer risk. Using mouse mammary tissue ex vivo, we show that testosterone-related progestins induce the PR target and mediator of PR signaling-induced cell proliferation receptor activator of NF-κB ligand (Rankl), whereas progestins with anti-androgenic properties in reporter assays do not. We develop intraductal xenografts of human breast epithelial cells from 36 women, show they remain hormone-responsive and that progesterone and the androgenic progestins, desogestrel, gestodene, and levonorgestrel, promote proliferation but the anti-androgenic, chlormadinone, and cyproterone acetate, do not. Prolonged exposure to androgenic progestins elicits hyperproliferation with cytologic changes. Androgen receptor inhibition interferes with PR agonist-and levonorgestrelinduced RANKL expression and reduces levonorgestrel-driven cell proliferation. Thus, different progestins have distinct biological activities in the breast epithelium to be considered for more informed choices in hormonal contraception.

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Section: Introductionmentioning

confidence: 99%