Classification and pharmacology of progestins

Schindler, A. E.; Campagnoli, C; Druckmann, René; Huber, Johannes; Pasqualini, Jörge R.; Schweppe, K.-W.; Thijssen, J. H. H.

doi:10.1016/j.maturitas.2003.09.014

Cited by 571 publications

(415 citation statements)

References 16 publications

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“…62−64 Besides progestagenic activity, synthetic norgestrel could also exhibit androgenic activity. 10,11 In addition to the parent compounds, those biodegradation products might have different biological effects. For example, the four androgens (Products 1−4) generated from progesterone could cause masculization of fish.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Degradation of Norgestrel by Bacteria from Activated Sludge: Comparison to Progesterone

Liu¹,

Ying²,

Yousheng³

et al. 2013

Environ. Sci. Technol.

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Natural and synthetic progestagens in the environment have become a concern due to their adverse effects on aquatic organisms. Laboratory studies were performed to investigate aerobic biodegradation of norgestrel by bacteria from activated sludge in comparison with progesterone, and to identify their degradation products and biotransformation pathways. The degradation of norgestrel followed first order reaction kinetics (T 1/2 = 12.5 d), while progesterone followed zero order reaction kinetics (T 1/2 = 4.3 h). Four and eight degradation products were identified for norgestrel and progesterone, respectively. Six norgestrel-degrading bacterial strains (Enterobacter ludwigii, Aeromonas hydrophila subsp. dhakensis, Pseudomonas monteilii, Comamonas testosteroni, Exiguobacterium acetylicum, and Chryseobacterium indologenes) and one progesterone-degrading bacterial strain (Comamonas testosteroni) were successfully isolated from the enrichment culture inoculated with aerobic activated sludge. To our best knowledge, this is the first report on the biodegradation products and degrading bacteria for norgestrel under aerobic conditions.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Degradation of Norgestrel by Bacteria from Activated Sludge: Comparison to Progesterone

Liu¹,

Ying²,

Yousheng³

et al. 2013

Environ. Sci. Technol.

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“…Although PgR seems to be important for the effects mediated by progestins, at least in a cell line harbouring high expression levels of the receptor such as T47D, there is a possibility that other steroid receptors could be involved when PgR is low or absent, and this may in part explain why the different cell lines respond differently to progesterone and different progestins. In addition to PgR, progestins have been reported to bind to GR, AR and MR, and also ER, and the extent to which these receptors are activated by different progestins may be dose dependent [23][24][25][26][27]. The failure of MPA to induce 17βHSD1-expression in T47D could be an indication that this progestin operates on other steroid receptors, e.g.…”

Section: Discussionmentioning

confidence: 99%

Progesterone and levonorgestrel regulate expression of 17βHSD-enzymes in progesterone receptor positive breast cancer cell line T47D

Sivik

Jansson

2012

Biochemical and Biophysical Research Communications

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The use of combined hormone replacement therapy (HRT) with oestrogens and progestins in postmenopausal women has been associated with an increased risk for developing breast cancer. The reasons are not fully understood, but influence of HRT on endogenous conversion of female sex hormones may be involved. The expression of 17 beta hydroxysteroid dehydrogenases (17βHSD), which are enzymes catalysing the conversion between more or less potent oestrogens, may partly be regulated by progestins. The breast cancer cell lines T47D, MCF-7 and ZR75-1 were treated with progesterone, medroxyprogesterone acetate (MPA) or levonorgestrel for 48 and 72 hours at 10 -7 M and 10 -9 M to investigate influence on 17βHSD1, 17βHSD2 and 17βHSD5 mRNA expression measured by real time PCR. The expression of 17βHSD1 increased in progesterone and levonorgestrel treated T47D cells (48h 10 -7 M P=0.002; P<0.001) and 17βHSD5 increased after progesterone treatment (48 h 10 -7 M P=0.003), whereas the expression of 17βHSD2 decreased after the (48 h 10 -7 M P=0.003; P<0.001). Similar, but less prominent effects were seen in MCF7 and ZR75-1. The progestin effects on 17βHSD-expression were lost when T47D-cells were co-treated with progestins and the progesterone receptor (PgR) inhibitor mifprestone. We show that both reductive (17βHSD1 and 17βHSD5) and oxidative (17βHSD2) members of the 17βHSD-family are under control of progesterone and progestins in breast cancer cell lines. This is most clear in T47D cells which have high PgR expression. 17βHSD enzymes are important players in the regulation of sex steroids locally in breast tumours and tumoural expression of various 17βHSD-enzymes have prognostic and treatment predictive relevance. We propose a mechanism for increased breast cancer risk after HRT in which hormone replacement affects the expression of 17βHSD-enzymes, favouring the expression of reductive enzymes, which in turn could increase levels of bioactive and mitogenic estrogens in local tissue, e.g. breast tissue.

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“…The deletion of the CH 3 radical in position C19 of the hydroxyprogesterone skeleton confers to the 19-norpregnane derivatives higher progestational potency when compared with pregnane, making these molecules to bind more selectively to the PGR. In particular, nomegestrol acetate, 19-norprogesterone and promegestone (R5020) are the most selective agonists of the PGR, with little or no activity for other steroid receptors (Sitruk-Ware 2002, Schindler et al 2003, García-Becerra et al 2004.…”

Section: Progestins Structurally Related To Progesteronementioning

confidence: 99%

“…Among these, there are the third-generation progestins (desogestrel or gestodene), derived from LNG group, developed to decrease androgenic activity (LeBlanc & Laws 1999), and the fourth-generation progestins. In this latter group, nomegestrol acetate exhibits partial anti-androgenic activity (Lello 2010, Van Diepen et al 2011) DNG, DRSP, and trimegestone have a significant anti-androgenic activity, whereas nestorone has no activity via the AR (Fotherby 1990, Philibert et al 1999, Schindler et al 2003.…”

Section: Figurementioning

confidence: 99%

The other side of progestins: effects in the brain

Giatti

Melcangi

Pesaresi

2016

Journal of Molecular Endocrinology

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Progestins are a broad class of progestational agents widely differing in their chemical structures and pharmacological properties. Despite emerging data suggest that progestins, besides their action as endometrial protection, can also have multiple nonreproductive functions, much remains to be discovered regarding the actions exerted by these molecules in the nervous system. Here, we report the role exerted by different progestins, currently used for contraception or in postmenopausal hormone replacement therapies, in regulating cognitive functions as well as social behavior and mood. We provide evidence that the effects and mechanisms underlying their actions are still confusing due to the use of different estrogens and progestins as well as different doses, duration of exposure, route of administration, baseline hormonal status and age of treated women. We also discuss the emerging issue concerning the relevant increase of these substances in the environment, able to deeply affect aquatic wildlife as well as to exert a possible influence in humans, which may be exposed to these compounds via contaminated drinking water and seafood. Finally, we report literature data showing the neurobiological action of progestins and in particular their importance during neurodegenerative events. This is extremely interesting, since some of the progestins currently used in clinical practice exert neuroprotective and anti-inflammatory effects in the nervous system, opening new promising opportunities for the use of these molecules as therapeutic agents for trauma and neurodegenerative disorders.

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Classification and pharmacology of progestins

Cited by 571 publications

References 16 publications

Degradation of Norgestrel by Bacteria from Activated Sludge: Comparison to Progesterone

Degradation of Norgestrel by Bacteria from Activated Sludge: Comparison to Progesterone

Progesterone and levonorgestrel regulate expression of 17βHSD-enzymes in progesterone receptor positive breast cancer cell line T47D

The other side of progestins: effects in the brain

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