Abstract:
:Trimegestone (TMG) is a novel 19-norpregnane progestin under development for hormone replacement therapy and oral contraception. The objective of the current study was to characterize the potency and steroid receptor selectivity of TMG in several in vitro assays and to compare its activity to that of medroxyprogesterone acetate (MPA). TMG and MPA had a similar competitive binding affinity for human and rabbit progesterone receptor (PR). However, TMG had a significantly higher affinity for rat PR (IC(50) = 3.3 nM) than MPA (IC(50) = 53.3 nM). In T47D cells, both compounds increased alkaline phosphatase activity and cell proliferation with comparable potencies (EC(50s) of 0.1 nM and of 0.02 nM, respectively). To further characterize the progestational activity and steroid receptor selectivity, we established an immortalized human endometrial stromal cell line (HESC-T). This cell line lacks endogenous estrogen receptor (ER) and PR but does have functional glucocorticoid receptors (GR). When ER is transiently expressed in the cells, 17beta-estradiol (E(2)) induces PR, allowing the study of PR-regulated genes. In HESC-T cells expressing exogenous ER, and therefore PR, both TMG and MPA increased HRE-tk-luciferase activity tenfold with an EC(50) of 0.2 nM. In HESC-T cells without exogenous ER, and therefore no PR, TMG did not induce HRE-tk-luciferase activity, whereas MPA induced the reporter activity with an EC(50) of about 10 nM. This MPA-induced reporter activity is believed to be mediated through GR. The steroid receptor selectivity of TMG was further evaluated using the HRE-tk-luciferase assay in the human lung carcinoma cell line A549, which contains GR but no PR. In these cells TMG had no effect on luciferase activity, whereas MPA increased the reporter activity in a dose-dependent manner with an EC(50) of approximately 30 nM. Furthermore, HRE-tk-luciferase assay in mouse fibroblast cell line L929, which expresses androgen receptor (AR) but no PR, showed that TMG had weak antiandrogenic activity whereas MPA had androgenic activity. In summary, data from several in vitro assays demonstrate that TMG is a potent progestin with a better receptor selectivity profile than MPA.
journal_name
Steroidsjournal_title
Steroidsauthors
Zhang Z,Lundeen SG,Zhu Y,Carver JM,Winneker RCdoi
10.1016/s0039-128x(00)00120-3subject
Has Abstractpub_date
2000-10-01 00:00:00pages
637-43issue
10-11eissn
0039-128Xissn
1878-5867pii
S0039128X00001203journal_volume
65pub_type
杂志文章相关文献
STEROIDS文献大全abstract::The 11 beta-hydroxysteroid dehydrogenase type II enzyme (11 beta HSD2) converts cortisol to cortisone, allowing the non-selective mineralocorticoid receptor to bind aldosterone. When the activity of this enzyme is compromised, as occurs in licorice intoxication or in the congenital syndrome of apparent mineralocortico...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(96)00013-x
更新日期:1996-04-01 00:00:00
abstract::The luteinizing hormone (LH) surge initiates a cascade of proteolytic events that control ovulation. One of the genes induced by LH is the progesterone receptor (PR). Because mice with a mutant PR gene (PRKO) fail to ovulate and are infertile, we have used them as a model in which to determine PR target genes that mig...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(00)00114-8
更新日期:2000-10-01 00:00:00
abstract::The leaky heme mutants G204, G216, and G214 are shown to accumulate exogenous sterols. Unlike hem mutants which have complete blocks in the heme pathway, these strains do not require ergosterol, methionine, or unsaturated fatty acids for growth. The addition of aminolevulinic acid to the growth medium inhibited sterol...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(89)90035-4
更新日期:1989-03-01 00:00:00
abstract::An homogenate from cortical tissue of mare adrenals was incubated in the presence of tritiated pregnenolone. The (3H) androstenedione and the (3H) testosterone synthesized during the incubation were extracted, purified, and co-crystallized to constant specific activity in the presence of unlabeled carriers. The rate o...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(84)90033-3
更新日期:1984-02-01 00:00:00
abstract::In comparison with the glucocorticoids cortisol and corticosterone, the mineralocorticoid aldosterone is a minority hormone of the mammalian adrenal cortex, and its proper function is dependent upon protective physiological mechanisms. These include a particular site of aldosterone synthesis in zona glomerulosa cells ...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/0039-128x(94)00021-4
更新日期:1995-01-01 00:00:00
abstract::Optimal assay conditions for cholesterol 7 alpha-hydroxylase activity in swine liver microsomes were determined. The enzyme activity is induced three-fold by feeding cholestyramine to the swine. This suggests that cholesterol 7 alpha-hydroxylase is likely to be the rate-limiting enzyme for biosynthesis of bile acids i...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(79)90008-4
更新日期:1979-03-01 00:00:00
abstract::To simultaneously measure some targeted endocrine disruptors and several forms of sex hormones in rat serum, an accurate analytical procedure was developed. First, a comparison between a polymeric-based solid-phase extraction (SPE) and a micro-extraction by packed sorbent was performed to choose the optimal method to ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2015.10.011
更新日期:2015-12-01 00:00:00
abstract::It has been previously demonstrated that 1,25 dihydroxyvitamin D(3) (1,25-D(3)) exerts inhibitory effects in breast cancer cells. The aim of this study was to determine whether mitogen-activated protein kinase (MAPK) pathways are associated with 1,25-D(3)-induced cell death in breast cancer. We used three breast cell ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2010.07.007
更新日期:2010-12-12 00:00:00
abstract::A facile method for the synthesis of a series of new steroidal 3-thioxamides from the 3-oxo compound, variously substituted at the 17 position, is described. The "one pot" reaction, using Lawesson's reagent (4-methoxyphenylthionophosphine sulphide dimer) in dichloromethane solution, gives the desired compounds with a ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(97)00003-2
更新日期:1997-06-01 00:00:00
abstract::A convenient procedure for the synthesis of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol via a modified homologation sequence of the intermediate 3 alpha,7 alpha,12 alpha-triformyloxy-24-oxo-25-diazo-25-homo-5 beta-cholane involving a homogeneous medium is described. This involves treating the intermediate alp...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(80)90144-0
更新日期:1980-04-01 00:00:00
abstract::Androgen-binding protein/sex hormone-binding globulin (ABP/SHBG) is an extracellular carrier protein that binds androgens and estrogens with high affinity. In the adult, ABP/SHBG is thought to function in the male reproductive system and the general circulation in both sexes to modulate the actions of sex steroids. Th...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(96)00049-9
更新日期:1996-07-01 00:00:00
abstract::Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2011.02.006
更新日期:2011-05-01 00:00:00
abstract::Ischemic heart disease (IHD) continues to be the most common cause of death globally, although mortality rates are decreasing with significant advances in treatment. Higher prevalence of co-morbidities in women only partly explains the lack of decrease in mortality rates in younger women due to. Until recently there h...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/j.steroids.2014.08.013
更新日期:2014-12-01 00:00:00
abstract::The left adrenal of two female dogs were perfused with either 3 muCi [4-14C]cpd. S (2) and 45 muCi [1, 2-3H] 21-deoxycortisone (Dog I), or with 1 muCi [4-14C] 17-hydroxyprogesterone and 65 muCi [1,2-3H] 21-deoxycortisone (Dog II). In Dog I, 40% of the perfused 21-deoxycortisone was converted to cortisone and 23% of cp...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(77)90078-2
更新日期:1977-08-01 00:00:00
abstract::The binding characteristics and quantitation of the recently reported fetal steroid binding protein (FSBP) cannot be determined on unpurified samples; an immunoassay was therefore desirable. The protein was purified to homogeneity in order to raise a highly specific polyclonal antibody. An enzyme-linked immunosorbent ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(85)90063-7
更新日期:1985-01-01 00:00:00
abstract::The condensation of O-substituted hydroxylamines with conjugated 3-oxo-4-en steroids results in a mixture of syn-anti configurations. Syn-anti ratios are influenced by sterical hindrance between the oximino substituents (e.g. O-benzyl) and the steroidal skeleton. Stereostructures and isomeric ratios were proved by det...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(98)00111-1
更新日期:1999-04-01 00:00:00
abstract::17 beta-Hydroxysteroid dehydrogenase (HSD) was studied in endometrium removed surgically from intact female monkeys in the luteal phase of the menstrual cycle. Also castrated monkeys (N=20) implanted with estradiol (E2) and progesterone (P) in silastic capsules were used to investigate the hormonal dependence of this ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(79)90139-9
更新日期:1979-01-01 00:00:00
abstract::Carbenoxolone potentiates the mineralocorticoid activity of endogenous glucocorticoid hormones by inhibiting the enzyme 11 beta-hydroxysteroid dehydrogenase, which converts cortisol and corticosterone to inactive 11-oxo-derivatives. We addressed the question of whether glucocorticoid activity is also affected by carbe...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(96)00252-8
更新日期:1997-04-01 00:00:00
abstract::Spermatozoa from bovine ejaculates and cauda epiditymidis were incubated with either tritiated 17 beta-hydroxy-5 alpha-androstane-3-one (DHT) or 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol). Examination of the medium incubations demonstrated metabolic conversion of both DHT and 3 alpha-diol when these steri...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(78)90045-4
更新日期:1978-03-01 00:00:00
abstract::The effect of attachment of a dimethylaminoethoxy or a dimethylaminopropoxy group at the 11 beta-position of estradiol (E2) on its relative binding affinity (RBA) to estrogen receptor (ER) and intrinsic biologic activity is described. The binding of 11 beta-[2-(N,N-dimethylamino) ethoxy]estra-1,3,5(10)-triene-3,17 bet...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(90)90022-4
更新日期:1990-05-01 00:00:00
abstract::The properties of 5-ene-3 beta hydroxysteroid oxidoreductase (3 beta-HSD) from human placental homogenates were studied in vitro. The apparent Michaelis constants for 3 beta-HSD with the substrates pregnenolone (delta 5P) and dehydroepiandrosterone (DHA) were 170 nM and nM respectively. The optimal pH for both these s...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(79)80002-1
更新日期:1979-01-01 00:00:00
abstract::It is known that follicle-stimulating hormone (FSH) and insulin stimulate estradiol secretion from cultured non-luteinizing granulosa cells. The interaction between these hormones is less well understood. Granulosa cells from small (2-4 mm) bovine follicles were cultured in serum-free medium to determine if cytochrome...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(00)00218-x
更新日期:2001-06-01 00:00:00
abstract::A series of novel 5α, 8α-endoperoxide steroidal hybrid derivatives containing isatin or indole substituents on the C-17 side chain were synthesized and characterized. The preliminary anti-proliferative activity of the compounds against HepG2, MCF-7, HT-29 and HeLa cell lines were investigated. Compounds 7g and 7l disp...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2019.108471
更新日期:2020-01-01 00:00:00
abstract::CGS 16949A inhibited the conversion of [4-14C]androstenedione (A) to [4-14C]estrone by human placental microsomes in a competitive manner (Ki = 1.6 nM). Aminoglutethimide, also a competitive inhibitor, had a Ki = 0.7 microM in this assay system. The Km for the aromatization of A was 0.11 microM. Using ovarian microsom...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(83)90068-5
更新日期:1987-07-01 00:00:00
abstract::Morphologic changes at the interface of rat endometrial luminal epithelial cells and the stromal cells immediately adjacent were examined and correlated with hypertrophy of the epithelial cells during estradiol (E2) infusion (1 microgram E2/24 h). While the lamina densa in castrate endometrium was thread-like, it beca...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(91)90061-y
更新日期:1991-03-01 00:00:00
abstract::Some properties of immunoreactive estradiol secreted by adrenals and ovaries of immature female rats were studied. It was shown that adrenals and ovaries of 15-day-old animals secrete approximately equal amounts of immunoreactive estradiol, with thin-layer chromatogram of immunoreactive material being identical for bo...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(92)90004-s
更新日期:1992-04-01 00:00:00
abstract::Using beta-sitosterol as a starting material, (6E)-hydroximino-24-ethylcholest-4-en-3-one (1), a natural steroidal oxime from Cinachyrella alloclada and C. apion, was synthesized in four steps with a high overall yield. First, beta-sitosterol (5a) is transformed into the corresponding 24-ethylcholest-4-en-3,6-dione (6...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2007.10.007
更新日期:2008-03-01 00:00:00
abstract::The uterine milk (UTM) proteins are the major progesterone-regulated proteins secreted by the sheep uterus during pregnancy. Recently, proteins related to the UTM proteins have been identified in uterine secretions of the pregnant cow and sow. The present objective was to determine the time course for induction of the...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(91)90022-n
更新日期:1991-12-01 00:00:00
abstract::Using a whole cell suspension assay technique, we have examined both the specific binding of testosterone (T) and dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) (DHT) and the subsequent distribution of androgen binding activity within MCF-7 human breast cancer cells. We have observed that both androgens...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(81)90078-7
更新日期:1981-10-01 00:00:00
abstract::Besides regulating water and electrolyte homeostasis, the mineralocorticoid receptor (MR) elicits pathophysiological effects in the renocardiovascular system. Although the MR's closest relative, the glucocorticoid receptor (GR), acts as a transcription factor at the same hormone-response-element (HRE), activated gluco...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/j.steroids.2009.10.006
更新日期:2010-08-01 00:00:00