The transcriptional activity of progestins used in contraception and menopausal hormone therapy via progesterone receptor A is dependent on the density of the receptor

Cartwright, Meghan; Toit, Renate Louw-du; Africander, Donita

doi:10.1016/j.bbrc.2022.11.077

Cited by 4 publications

(2 citation statements)

References 29 publications

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“…Synthetic estrogens act by modulating the transcription of target genes (Coons and Korach, 2023), as well as progestins (Cartwright et al, 2023). Previous studies presented in this review suggest that genes expressed in the hippocampus and/or amygdala and implicated in ASD (amygdala) and psychosis (both brain regions) may be affected by in utero exposure to progestins and/or synthetic estrogens.…”

Section: Discussion and Conclusion: Other Avenues To Explorementioning

confidence: 82%

“…Like natural progesterone, progestins activate the two progesterone receptor (PR) isoforms: PR-A and PR-B. Cartwright et al wrote that "Both isoforms can regulate transcription by the classical mechanism of either enhancing gene expression via the direct binding to progesterone response elements in the promoter region of specific target genes or by repressing gene expression through tethering to DNA-bound transcription factors" (Cartwright et al, 2023). Moreover, the authors suggested that progestin effects via PR-A are influenced by the receptor density.…”

Section: Synthetic Progestogens (Progestins)mentioning

confidence: 99%

See 1 more Smart Citation

Effects of prenatal exposure to synthetic sex hormones on neurodevelopment: a biological mechanism.

Soyer-Gobillard,

Gaspari,

Paris

et al. 2023

Front. Mol. Neurosci.

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Since the middle of the 20th century, synthetic sex hormones (estrogens and progestins) have been administered to millions of pregnant or not women worldwide, mainly to avoid miscarriage or for comfort, although their mode of action and their effects on the mother and fetus were ignored. Despite the alerts and the description of somatic and psychiatric disorders in children exposed in utero, synthetic estrogens were prohibited for pregnant women only in the 1970s and 1980s, but some progestins are still authorized. In this review, we summarize the psychiatric disorders described in children exposed in utero to such hormones, focusing particularly on schizophrenia, bipolar disorders, severe depression, eating disorders, suicide and suicide attempts. Moreover, only in 2017 the mechanism of action of these xenohormones has started to be deciphered. Some studies showed that in the fetus exposed in utero, they alter the DNA methylation profile (mainly hypermethylation), and consequently the expression of genes implicated in neurodevelopment and in regulating the sexual organ morphogenesis and also of the promoter of estrogen receptors, located in the amygdala. These deleterious effects may be transmitted also to the next generations, thus affecting the children directly exposed and also the following generations.

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Section: Discussion and Conclusion: Other Avenues To Explorementioning

confidence: 82%

Section: Synthetic Progestogens (Progestins)mentioning

confidence: 99%