Hormonal properties of norethisterone, 7α-methyl-norethisterone and their derivatives

@article{Schoonen2000HormonalPO,
  title={Hormonal properties of norethisterone, 7$\alpha$-methyl-norethisterone and their derivatives},
  author={Willem G.E.J. Schoonen and Godefrides H Deckers and Marcel Evert De Gooijer and R de Ries and Helenius Jan Kloosterboer},
  journal={The Journal of Steroid Biochemistry and Molecular Biology},
  year={2000},
  volume={74},
  pages={213-222}
}
Norethisterone (NET) is a progestagenic compound with very weak androgenicity and estrogenicity. These low androgenic and estrogenic activities may be attributed to NET itself or induced by metabolites of NET. In order to improve the bioactivity of NET, the effects of a 7alpha-methyl substitution were studied. Thus this study has two objectives: first the comparison between biological activities of NET and 7alpha-methyl-NET (MeNET), and second the biological activity of tentative metabolites of… Expand
View on Elsevier
doi.org
70 Citations
Highly Influential Citations
6
Background Citations
17
Methods Citations
6
Results Citations
1

70 Citations

Citation Type

Citation Type

Estrogenic effects of 7α-methyl-17α-ethynylestradiol: a newly discovered tibolone metabolite
Abstract Tibolone is a synthetic steroid that is prescribed to postmenopausal women for relief of climacteric symptoms and prevention of osteoporosis. It has been reported to be metabolized in a… Expand
A comparative study of the androgenic properties of progesterone and the progestins, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-A)
TLDR
This study is the first to determine accurate apparent Ki values for Prog, MPA and NET-A toward the human AR in COS-1 cells, and reveals that these ligands have a similar binding affinity for the AR to that of the natural androgen 5α-dihydrotestosterone (DHT). Expand
Synthetic progestins used in HRT have different glucocorticoid agonist properties
TLDR
Results suggest that the differences in biological activity of the progestins are not merely due to differences in their affinity for the GR but also due to the induction of different conformational changes in the liganded-GR. Expand
An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells
TLDR
NOMAC is a progestin that has greater steroid receptor selectivity compared to MPA or some other synthetic progestins and may provide a better pharmacological profile than those progests currently in use in HRT and OC. Expand
Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue
TLDR
This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients. Expand
Nomegestrol acetate, a novel progestogen for oral contraception
TLDR
In a phase III study, NOMAC/E2 provided consistent and robust ovulation inhibition, with contraceptive effects that compared favorably with those of drospirenone 3mg/ethinyl estradiol (EE) 30 μg. Expand
Effects of progesterone and norethindrone on female fathead minnow (Pimephales promelas) steroidogenesis.
TLDR
Overall, this study showed that exposure to a natural progestogen (progesterone) and synthetic progestin (norethindrone), was capable of modulating LHβ (in brain) and mPRβ expression (in ovary). Expand
Induction of androgen receptor activity by norgestimate and norelgestromin in MDA-MB 231 breast cancer cells
TLDR
The data suggest that norgestimate and its metabolite norelgestromin possess weak androgen-like properties and the use of these compounds for clinical application may be of great advantage in the treatment of breast cancer as well as hyperandrogenism in women. Expand
Norethisterone is bioconverted to oestrogenic compounds that activate both the oestrogen receptor α and oestrogen receptor β in vitro
TLDR
It is demonstrated that CV-1 and T-47D cells possess the enzymatic machinery to bioconvert norethisterone into the 5α-reduced, 3α-hydroxylated form and that neither 3α,5α- or 3β,5 α-norethistersone exhibit preference or selectivity towards a particular oestrogen receptor isoform to induce a particular Oestrogenic effect in these cell lines. Expand
Differential regulation of endogenous pro-inflammatory cytokine genes by medroxyprogesterone acetate and norethisterone acetate in cell lines of the female genital tract.
TLDR
This study is the first to show ligand-, promoter- and cell-specific regulation of IL-6, IL-8 and RANTES gene expression by Prog, MPA and NET-A in these cell lines, and highlights the importance of choice of progestins for immune function in the cervicovaginal environment. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 25 REFERENCES
Norethisterone metabolites modulate the uteroglobin and progesterone receptor gene expression in prepubertal rabbits.
TLDR
The inhibition of UG synthesis and PR down-regulation by 5 alpha- NET and 3 beta,5 alpha-NET indicates that these NET metabolites possess antiprogestational properties. Expand
The metabolism of 19-nor contraceptive progestins modulates their biological activity at the neuroendocrine level.
TLDR
Findings underline the importance of the metabolic rate of NET for the expression of its biological effects at the hypothalamic-pituitary unit and the observed in vivo estrogenic effects of the parent compound. Expand
Intrinsic estrogenicity of some progestagenic drugs
TLDR
A recently developed in vitro method to estimate estrogenic activities is applied, which is based on measurements of the estrogen-stimulated alkaline phosphatase activity in cells of the Ishikawa-Var I human endometrial adenocarcinoma line, a response not influenced by progestins. Expand
The biological activity of 7 alpha-methyl-19-nortestosterone is not amplified in male reproductive tract as is that of testosterone.
TLDR
Observations show that 7 alpha-methylated androgens can maintain muscle mass and normal gonadotropin levels in androgen deficient rats without hyperstimulating the prostate, suggesting that these androgens may offer some health benefits to men who require androgen treatment. Expand
Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens
Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive tract (androgenic effects) and growth of non-reproductive… Expand
Endocrinological studies with (7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14).
A novel steroid, (7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14), is described which has concomitant weak estrogenic, progestational and androgenic activities.… Expand
A comparison of the potencies and activities of progestogens used in contraceptives.
TLDR
Levonorgestrel was more androgenic than desogestrel, and P, norethindrone, norgestimate and MPA were essentially devoid of androgen activity, demonstrating clear differences in the potencies and activities of these progestogens and in their selectivity for target organs. Expand
In vitro evaluation of estrogenic, estrogen antagonistic and progestagenic effects of a steroidal drug (Org OD-14) and its metabolites on human endometrium.
TLDR
The estrogenic and progestagenic actions of these compounds are in general agreement with their relative affinity for binding to the estradiol and progesterone receptors, although their actions may be influenced by intracellular metabolism in the endometrial tissue. Expand
In Vitro Metabolism of 7α-Methyl-19-Nortestosterone by Rat Liver, Prostate, and Epididymis
TLDR
The in vitro metabolism of 7α-methyl- 19-nortestosterone was investigated in male rat liver, ventral prostate, and epididymis and it is concluded that the androgenic potency of the steroid is not dependent on its further conversion to 5α-dihydro-metabolites. Expand
Metabolic profiles of endogenous and ethynyl steroids in plasma and urine from women during administration of oral contraceptives.
TLDR
The concentrations of steroids in plasma during contraception were similar to those during the follicular and mid phases of the menstrual cycle, whereas levels of progesterone metabolites were higher in the luteal phase and urinary excretion of steroids was 15-30% lower during the contraceptive cycle. Expand
...
1
2
3
...