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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our purpose was to examine the roles of natural (estradiol (E2) and estrone (E1)) and synthetic estrogens (ethinyl estradiol (EE), moxestrol (MOX), and tamoxifene (TAM)) in regulating production of sex hormone-binding globulin (SHBG) by human hepatoma G2 (Hep G2) cells, the rationale being that synthetic estrogens are less rapidly metabolized than natural estrogens and, thus, may alter SHBG levels more readily. In Hep G2 cells, E2, E1, and EE at 10(-7) M did not result in significantly greater SHBG secretion compared to control cells. The synthetic estrogens, MOX and TAM, caused significant, P < 0.001, increases of 30% and 51% in SHBG secretion at 10(-7) M compared to controls. However, when TAM and E2 were added together, each at 10(-7) M, no increase in SHBG secretion was noted. We conclude that natural estrogens at physiologic concentrations do not increase SHBG secretion by Hep G2 cells, but the increase of SHBG secretion caused by MOX and TAM suggests that the lack of effect of E2 and E1 may, in part, be due to their rapid metabolism. In addition, TAM stimulates SHBG secretion by interaction with the genome that is different, in certain respects, from that of E2.
Steroids 2001 Aug
PMID:Regulation of sex hormone-binding globulin secretion in human hepatoma G2 cells. 1143 Sep 92

The interactions of estrogens and progestins in producing decidualization, deciduosarcoma. and other lesions in the rabbit were explored. Steroids were delivered by silicone elastomer implants placed subdermally except for oral dosing in 1 experiment. Varying doses of levonorgestrel (LNG) were given with and without estradiol (E2) and varying doses of E2 with and without LNG. LNG alone delivered at an estimated mean dose of 233 microg/day did not result in endometrial decidualization or deciduosarcoma. Both conditions occurred when E2 was added to the regimen and increased as the dose of E2 was increased. Sixty microg of E2 per day produced endometrial decidualization in all test animals in a 2-month exposure, but deciduosarcoma occurred only when LNG was also supplied and increased as the LNG dose was increased. Progesterone given with E2 resulted in deciduosarcoma in most rabbits. Ethynylestradiol alone at 30 microg/day delivered by implants produced splenic and ovarian deciduosarcomas in 1 of 5 test animals. Adding LNG resulted in more numerous and widespread deciduosarcomas. These experiments indicate that exogenous estrogen is necessary for decidualization of the endometrium and to production of deciduosarcoma in the nonpregnant rabbit. Exogenous progestin promotes the process. Necrosis of the uterine wall tended to increase with increasing dose of estrogens.
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PMID:The roles of estrogen and progestin in producing deciduosarcoma and other lesions in the rabbit. 1156 Feb 46

Preparative chemical methods for the synthesis of eight oxidative transformation products of ethinyl estradiol (EE) and norethindrone acetate (NA) are described. The prepared materials are useful as reference materials and standards for pharmaceutical analysis of EE and NA as bulk chemical or in formulated product. All eight products result from oxidation of the A and/or B rings of the parent compounds. Oxidation of the heteroannular 3,5 dienyl acetate derivative of NA resulted in the 6 alpha-hydroxy, 6 beta-hydroxy and 6-keto NA. Oxidation of 6-keto NA led to the preparation of 6 alpha-hydroxy, 6 beta-hydroxy, 6-keto- and Delta(6) EE. Delta(11) EE was prepared from estrone.
Steroids 2002 Mar
PMID:Norethindrone acetate (NA) and ethinyl estradiol (EE) related oxidative transformation products in stability samples of formulated drug product: synthesis of authentic references. 1185 40

Estrogen promotes endothelial cell proliferation and survival in the vasculture of non-reproductive organs. The main mechanisms through which estrogen exerts its effects on endothelial cells remain unknown. Angiopoietins are newly described modulators of endothelial cell survival and they exert their effects through the activation of endothelial cell-specific Tie-2 receptors. In this study, we evaluated whether estrogen modulates the activity and expression of Tie-2 receptors, Ang-1 and its endogenous antagonist; angiopoietins-2 (Ang-2) in non-reproductive organs. Using RT-PCR, we found that daily administration of 17-beta-estradiol for 8 days in ovariectomized rats results in a significant reduction in tissue Ang-1 mRNA expression. By comparison, estrogen therapy produced a significant increase in Ang-2 mRNA in estrogen-treated rats with heart, kidney and lung Ang-2 mRNA levels reaching 169%, 152% and 224% of those of oil-treated animals, respectively. We also observed that tyrosine phosphorylation of Tie-2 receptors is significantly attenuated in ovariectomized rats treated with 17-beta-estradiol. Our results suggest that the effects of estrogen on the vasculature of non-reproductive organs require the inhibition of angiopoietin-1-Tie-2 receptor pathway and that this inhibition is achieved through simultaneous down-regulation of Ang-1 and Tie-2 expression and elevation in Ang-2 expression.
Steroids 2002 Mar
PMID:Regulation of angiopoietin and Tie-2 receptor expression in non-reproductive tissues by estrogen. 1185 54

Estrogen has important atheroprotective and vasoactive properties related to its capacity to stimulate nitric oxide (NO) production by endothelial NO synthase. Previous work has shown that these effects are mediated by estrogen receptor (ER) alpha functioning in a nongenomic manner via calcium-dependent, MAP kinase-dependent mechanisms. Recent studies have demonstrated that estradiol (E(2)) activates eNOS in isolated endothelial plasma membranes in the absence of added calcium, calmodulin or eNOS cofactors. Studies of blockade by ICI 182,780 and by ER alpha antibody, and also immunoidentification experiments indicate that the process is mediated by a subpopulation of plasma membrane-associated ER alpha. Fractionation of endothelial cell plasma membranes has further revealed that ER alpha protein is localized to caveolae, and that E(2) causes stimulation of eNOS in isolated caveolae which is ER-dependent and calcium-dependent, whereas noncaveolae membranes are insensitive. Furthermore, in intact endothelial cells the activation of eNOS by E(2) is prevented by pertussis toxin, and exogenous GDP beta S inhibits the response in isolated plasma membranes. Coimmunoprecipitation studies have shown that E(2) exposure causes interaction between ER alpha and G(alpha i) on the plasma membrane, and eNOS activation by E(2) is enhanced by overexpression of G(alpha i) and attenuated by expression of a protein regulator of G protein signaling (RGS), RGS4. Thus, a subpopulation of ER alpha is localized to caveolae in endothelial cells, where they are coupled via G(alpha i) to eNOS in a functional signaling module. Emphasizing the dependence on cell surface-associated receptors, these observations provide evidence for the existence of a steroid receptor fast-action complex, or SRFC, in caveolae.
Steroids 2002 May
PMID:Rapid activation of endothelial NO synthase by estrogen: evidence for a steroid receptor fast-action complex (SRFC) in caveolae. 1196 Jun 16

Here we report on the progress we have made in elucidating the mechanisms through which estrogen alters synaptic responses in hypothalamic neurons. We examined the modulation by estrogen of the coupling of various receptor systems to inwardly rectifying and small conductance, Ca(2+)-activated K(+) (SK) channels. We used intracellular sharp-electrode and whole-cell recordings in hypothalamic slices from ovariectomized female guinea pigs. Estrogen rapidly uncouples mu-opioid receptors from G protein-gated inwardly rectifying K(+) (GIRK) channels in beta-endorphin neurons, manifest by a reduction in the potency of mu-opioid receptor agonists to hyperpolarize these cells. This effect is blocked by inhibitors of protein kinase A and protein kinase C. Estrogen also uncouples gamma-aminobutyric acid (GABA)(B) receptors from the same population of GIRK channels coupled to mu-opioid receptors. At 24 h after steroid administration, the GABA(B)/GIRK channel uncoupling observed in GABAergic neurons of the preoptic area (POA) is associated with reduced agonist efficacy. Conversely, estrogen enhances the efficacy of alpha(1)-adrenergic receptor agonists to inhibit apamin-sensitive SK currents in these POA GABAergic neurons, and does so in both a rapid and sustained fashion. Finally, we observed a direct, steroid-induced hyperpolarization of both arcuate and POA neurons, among which gonadotropin-releasing hormone (GnRH) neurons are particularly sensitive. These findings indicate a richly complex yet coordinated steroid modulation of K(+) channel activity that serves to control the excitability of hypothalamic neurons involved in regulating the reproductive axis.
Steroids 2002 May
PMID:Estrogen modulation of K(+) channel activity in hypothalamic neurons involved in the control of the reproductive axis. 1196 Jun 20

Estrogen receptors (ER) are expressed not only in the reproductive system and ovaries but also in some other tissues, including the adrenal gland. The purpose of this study was to assess the association between the estrogen receptor (ER) alpha gene polymorphisms XbaI and PvuII and circulating levels of androstenedione, a precursor of sex-steroids synthetized in the ovary and adrenal. After adjustment for years since menopause, body mass, and dehydroepiandrosterone (DHEA) levels, a highly significant relationship was demonstrated between androstenedione and XbaI or PvuII polymorphisms, the highest levels of the hormone being found in the xx and pp genotypes (P<0.05 as compared to XX or PP, ANCOVA followed by least significant difference (LSD) multiple comparisons). This suggests that the ER genotype may determine the function of the sex-steroid system not only at the receptor level but also at the level of hormone synthesis. The pathogenetic role of this association in diseases related to menopause, such as osteoporosis, remains to be determined.
Steroids 2002 Sep
PMID:The estrogen receptor alpha gene determines serum androstenedione levels in postmenopausal women. 1223 Nov 16

To evaluate the effect of a progestinic-estrogenic combination on human adrenal function 2 different ratios were given, 1 pill a day for 20 consecutive days from Day 5 to Day 24 of the ovarian cycle. Medroxyprogesterone acetate, 5 mg, with ethinyl estradiol, 50 mcg, (MAP-5-EE-50) and medroxyprogesterone acetate, 2 mg, with ethinylestradiol, 75 mcg (MAP-2-EE-75) were given to 8 women. Adrenal function was determined before, during, and after therapy and urinary 17-ketosteroids (17-KA), 17-hydroxycorticosteroids (17-OHCS), pregnanediol and pregnanetriol were measured. To stimulate the adrenals iv infusion of .25 mg synthetic ACTH was administered over a period of 6 hours. Stimulation of the pituitary-adrenal axis was done by giving 4.5 gm metopirone in 6 doses in 1 day. In all subjects a definite increase of plasma corticoids was found after 20 days of therapy. In 6 of the 8 cases a definite decrease of urinary 17-OHCS was observed. Pregnanetriol excretion decreased in all cases. Pregnanediol excretion, as determined in the urine throughout the luteal phase of the ovarian cycle, was decreased by both dosages, indicating a blockage of ovulation. Urinary excretion of tetrahydrocortisol and tetrahydrocortisone was decreased in all 5 cases studied. To investigate possible change in cortisol metabolism the percentage of free and conjugated 17-OHCS was determined in 4 cases. Values were unchanged. Half-life of injected cortisol was increased and secretion rate of endogenous cortisol reduced. Added tritiated cortisol in vitro has shown a higher cortisol binding capacity of human plasma after progestinic-estrogenic therapy. Administration of ACTH in 3 cases showed an adrenal response equal to that obtained before treatment, indicating adrenal reserve had been maintained. Hypothalamic-pituitary-adrenal function, as determined with metropione, showed a decrease of urinary adrenal metabolites in all cases. Results show that the 2 doses given block ovulation and that progesterone is not produced by a corpus luteum. The progestinic-estrogenic therapy, in both doses, modified the metabolism of cortisol in the same way as estrogens alone do.
Res Steroids (Amst) 1966
PMID:Effect of a progestinic-estrogenic combination on human adrenal function. 1230 25

Estrogen levels vary in a cyclic fashion during the rat estrous cycle, reaching peak concentrations during proestrus. Previously, it was suggested that the preovulatory peak in estrogen production in rats in vivo is regulated by other control mechanisms than concentration of precursor and amount of aromatase enzyme, changing the specific activity of the enzyme. To explore this hypothesis, ovarian binding of [11C]vorozole in vivo and in vitro, representing the amount of active aromatase, and conversion activity of ovarian homogenate were assayed together with serum androstenedione (A4) and estradiol-17beta (E2) levels during the estrous cycle in rats. The reducing ovarian [11C]vorozole binding in vivo from proestrus +4 up to +8h might indicate that the ovarian aromatase is blocked, probably to prevent premature increase of E2 levels. Thereafter (between proestrus +9 and +13h), the binding dramatically increases (aromatase enzyme is unblocked), to enable increased E2 synthesis. In addition, during the latter period, serum E2 levels were strongly correlated with serum A4 levels after adjustment for amount of ovarian aromatase (P=0.03), but not with amount of aromatase adjusted for levels of A4 (P=0.13), which might indicate changes in specific activity of the aromatase enzyme. Significant correlation between Kd and serum E2 levels during the same period indicated that aromatase-precursor affinity might be involved in the regulation of the enzyme-specific activity. This conclusion is done assuming that [11C]vorozole binding mimics that of the substrate (A4). The [11C]vorozole in vivo technique keeps auto- and paracrine mechanisms intact, and might therefore yield additional information about biological processes compared with traditional in vitro techniques.
Steroids 2003 Dec
PMID:Characterization of [11C]vorozole binding in ovarian tissue in rats throughout estrous cycle in association with conversion of androgens to estrogens in vivo and in vitro. 1464 75

Progesterone is more than a progestin. Beyond functions in cycle and pregnancy, progesterone binds with high affinity to the mineralocorticoid receptor (MR) acting as an antagonist, with obvious significance for electrolyte homeostasis, an array of MR-related functions in the circulation as well as in the CNS. Progesterone induces natriuresis at physiological concentrations. Lack of antimineralocorticoid activity with conventional progestins may account for sodium and water retention, minor elevation of blood pressure and "pill hypertension" in susceptible women on oral contraceptives. Ethinylestradiol (EE) contributes to this problem by distinct activation of the renin-angiotensin-aldosterone (RAAS) system. Drospirenone (DRSP: 6beta,7beta,15beta,16beta-dimethylene-3-oxo 17alpha-pregn-4-ene-21,17 carbolactone) is the first synthetic progestin with antialdosterone activity. DRSP and progesterone bind to PR in uterine (affinity of both is about 30% of R5020) and MR in kidney cytosol (affinity about 230 and 100% of aldosterone, respectively). Intrauterine administration of DRSP in silastic tubes induced maximum local progestational effects in rabbits. At systemic subcutaneous (s.c.) administration (McPhail-assay) full endometrial transformation was obtained at 1mg per animal per day. At 1-3mg DRSP per animal per day subcutaneously, pregnancy maintenance after ovariectomy, antiovulatory activity, and antimineralocorticoid activity were seen in the respective assays in rats. The latter activity indicates about eight-fold higher potency than spironolactone. DRSP decreased blood pressure in male hypertensive rats, whereas an increase was noted under conventional progestins. DRSP also prevented hypertension and fetal growth retardation in pregnant rats after L-NAME, an inhibitor of nitric oxide synthase. DRSP has antiandrogenic activity. Feminizing effects were recorded during sexual differentiation in male fetuses at high doses. Powerful antiandrogenic effects were also seen in gonad intact and testosterone substituted castrated male rats. The antiandrogenic potency of DRSP is superior to that of spironolactone but below that of cyproterone acetate. Endometrial transformation, inhibition of ovulation, and antimineralocorticoid, i.e. natriuretic effects and mild antiandrogenic effects were recorded at the same range of oral doses (0.5-4 mg per day) in humans. Combined with EE (3 mg DRSP+30 microg EE), DRSP provides effective inhibition of ovulation and cycle control. Body weight compared to conventional oral contraceptives was reduced. DRSP (3 mg per day+15, 20, or 30 microg ethinyl estradiol per day) prevented the mild increase of blood pressure seen under a conventional levonorgestrel-containing contraceptive and even tended to reduce pretreatment blood pressure. Studies on modulation (i.e. inhibition) of glucocorticoid effects at the MR in the CNS remain an unexplored and interesting area for research.
Steroids 2003 Nov
PMID:Conception and pharmacodynamic profile of drospirenone. 1466 81


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