The effect of progesterone and estradiol on basal and oxytocin-stimulated prostaglandin F(2 alpha) production and on oxytocin receptor concentrations in endometrium from long term ovariectomized cows was investigated using an explant culture system. Uteri were obtained from cows at slaughter and endometrial explants were cultured in triplicate for up to 96 h in either control media, or media containing progesterone or estradiol. Basal prostaglandin F(2 alpha) production was unaffected by progesterone treatment but was stimulated by estradiol treatment in a dose dependent manner. Oxytocin receptor concentrations remained unchanged in control culture and were unaffected by treatment with estradiol while treatment with progesterone caused a dose-dependent inhibition. Responsiveness to oxytocin, in terms of increased prostaglandin F(2 alpha) production, developed "spontaneously" over the first 24 h of culture and was unaffected by treatment with progesterone or estradiol. In summary the results reveal a dose-dependent inhibition of oxytocin receptor concentration by progesterone and a dose-dependent stimulation of basal PGF(2 alpha) release by estradiol. The reason for the "spontaneous" development of responsiveness to oxytocin remains unknown but may result from the removal of tissue from the influence of an, as yet unidentified, inhibitory factor.
J Clin Endocrinol Metab. 2001 Jul;86(7):3039-44.
Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls.
Ankarberg-Lindgren C, Elfving M, Wikland KA, Norjavaara E.
Goteborg Pediatric Growth Research Center, Institute for the Health of Women and Children, Goteborg University, Sweden.
The objective of pubertal induction in children with hypogonadism is to mimic spontaneous puberty in terms of physical and psychological development. In a clinical observation study, we induced puberty in 15 girls with hyper- or hypogonadotropic hypogonadism using low doses of transdermal estradiol patches attached only during the night and compared the estradiol concentrations obtained with those in healthy girls. Pubertal induction was started between the ages of 12.3 and 18.1 yr. A transdermal matrix patch of 17beta-estradiol (25 microg/24 h; Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1, 4.2, or 6.2 microg/24 h initially and attached to the buttock. After 4-14 months, the dose was increased gradually. Serum 17beta-estradiol concentrations were measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL). The results show that it is possible to mimic the spontaneous levels as well as the diurnal pattern of serum 17beta-estradiol in early puberty, by cutting a transdermal 17beta-estradiol matrix patch and attaching a part of it, corresponding to 0.08-0.12 microg estradiol/kg BW, to the buttock nocturnally. In most of the girls, breast development occurred within 3-6 months of the start of treatment.
Endocrine. 2001 Apr;14(3):343-8.
Effects of cortisol and estradiol on pituitary expression of proopiomelanocortin, prohormone convertase-1, prohormone convertase-2, and glucocorticoid receptor mRNA in fetal sheep.
Holloway AC, Whittle WL, Challis JR.
Department of Physiology, University of Toronto, Ontario, Canada. alison.hollowatoronto.ca
We hypothesized that in the late-gestation sheep fetus there is an interaction between the prepartum rise in cortisol and the increase in placental estradiol production that allows expression of key components of the fetal hypothalamic-pituitary-adrenal (HPA) axis. Therefore, the goal of this study was to investigate the effects of cortisol on the fetal HPA axis in the presence and absence of increased placental estradiol production. We obtained fetal plasma samples and pituitary tissue from animals that had received an infusion of either cortisol, cortisol and 4-hydroxyandrostenedione (40HA, an aromatase inhibitor), saline, or saline + 40HA controls. Cortisol significantly decreased plasma adrenocorticotropic hormone concentrations, and in the presence of 40HA reduced pituitary proopiomelanocortin (POMC) mRNA levels in the pars distalis. There was no effect of any treatment on the expression of the key POMC processing enzymes, prohormone convertase-1 or -2 in the fetal pituitary. Conversely, levels of glucocorticoid receptor (GR) mRNA in the pituitary were increased with cortisol treatment in the absence of increased estradiol. We suggest that in the late-gestation sheep fetus, cortisol and estradiol have opposite effects on pituitary POMC and GR mRNA expression, and interact to regulate these key components of the fetal HPA axis.
Drug Dev Ind Pharm. 2001 May;27(5):431-7.
Acrylic resins as rate-controlling membranes in novel formulation of a nine-day 17beta-estradiol transdermal delivery system: in vitro and release modifier effect evaluation.
Rafiee-Tehrani M, Safaii-Nikui N, Peteriet H, Beckert T.
College of Pharmacy, Tehran University of Medical Sciences, Iran.
The feasibility of transdermal controlled delivery system of 17beta-estradiol was investigated by conducting in vitro release studies. Several new 17beta-estradiol unilaminate adhesive devices capable of releasing 17beta-estradiol in a controlled fashion over a 24-h, 36-h, 96-h, 104-h, 168-h, and 216-h period have been developed using acrylic resins (Eudragits E100, RSPO, and RLPO) as adhesive and rate-controlling polymers. The in vitro release profiles of 17beta-estradiol from various TDS unilaminate devices were characterized in a new developed dissolution tester vessel (total volume 200 ml), using a new paddle. The release of drug from different formulations was measured by a sensitive high-performance liquid chromatographic (HPLC) method. The release of drug from all prepared adhesive devices seems to obey zero-order kinetics (r > 0.98). The effect of two different plasticizers (acetyltriburyl citrate [ATBC] and triethyl citrate [TEC]) on the release patterns of 17beta-estradiol from TDS formulations was studied, and they were almost identical. The effect of two different release modifiers, propylene glycol (PG) and myristic acid (MA), on the release pattern of 17beta-estradiol from prepared unilaminate devices was evaluated. It was shown that the use of these release modifiers significantly increased the release of 17beta-estradiol from a TDS unilaminate patch. Furthermore, these data clearly demonstrated that the acrylic resins are suitable polymers for the preparation of 17beta-estradiol TDS adhesive devices.
Mol Cell Biochem. 2001 Apr;220(1-2):87-93.
Estrogen increases hepatic lipase levels in inbred strains of mice: a possible mechanism for estrogen-dependent lowering of high density lipoprotein.
Srivastava N, Chowdhury PR, Averna M, Srivastava RA.
Department of Internal Medicine, Washington University, St. Louis, MO, USA.
We have shown mouse to be an useful animal model for studies on the estrogen-mediated synthesis and secretion of lipoproteins since, unlike in rats, low density lipoprotein receptors are not upregulated in mice. This results into the elevation of plasma levels of apolipoprotein (apo) B and apoE, and lowering of apoA-1-containing particles. The mechanisms of apoB and apoE elevation by estrogen have been elucidated, but the mechanism of lowering of plasma levels of HDL is still not known. Among other factors, apoA-I, cholesterol ester transfer protein (CETP), scavenger receptor B1 (SR-B1), and hepatic lipase are potential candidates that modulate plasma levels of HDL. Since estrogen treatment increased hepatic apoA-I mRNA and apoA-I synthesis, and mouse express undetectable levels of CETP, we tested the hypothesis that estradiol-mediated lowering of HDL in mice may occur through modulation of hepatic lipase (HL). Four mouse strains (C57L, C57BL, BALB, C3H) were administered supraphysiological doses of estradiol, and plasma levels of HDL as well as HL mRNA were quantitated. In all 4 strains estradiol decreased plasma levels of HDL by 30%, and increased HL mRNA 2-3 fold. In a separate experiment groups of male C57BL mouse were castrated or sham-operated, and low and high doses of estradiol administered. We found 1.4-2.5 fold elevation of HL mRNA with concomitant lowering of HDL levels. Ten other mouse strains examined also showed estradiol-induced elevation of HL mRNA, but the extent of elevation was found to be strain-specific. Based on these studies, we conclude that hepatic lipase is an important determinant of plasma levels of HDL and that HL mRNA is modulated by estrogen which
Exp Clin Endocrinol Diabetes. 2001;109(4):231-7.
Regulation of estrogen receptor alpha and progesterone receptor (isoform A and B) expression in cultured human endometrial cells.
Prange-Kiel J, Rune GM, Zwirner M, Wallwiener D, Kiesel L.
Institut of Anatomy, Ernst-Moritz-Arndt University, Greifswald, Germany. prangail.uni-greifswald.de
The effects of RU 486 together with estradiol and progesterone on estrogen receptor alpha and progesterone receptor (isoforms A and B) expression were studied in human endometrial long term cultures at the mRNA and protein level. We asked whether ligand induced receptor regulation, found in mammals in vivo, is also found in human cultured endometrial cells with special regard to the progesterone isoforms A and B. Endometrial cultures were maintained for 27 days. Media were supplemented with progesterone and/or estradiol alone or in combination with RU 486. Receptor expression (estrogen receptor alpha and progesterone receptor isoform A and B) was examined at the mRNA level by RT-PCR and at the protein level by western blot analysis. All receptor types examined were expressed in our culture model. Estradiol led to a general increase of receptor expression whereas treatment with estradiol in combination with progesterone down regulated receptor expression. The receptor down regulation was not found when RU 486 was additionally supplemented into the medium. Activation or inhibition of expression due to these treatments was similar for both PR isoforms. Our results (1) show that in our culture system estradiol induced up regulation of estrogen receptor and progesterone receptor A and B and suggest that the estrogen induced up regulation is prevented by progesterone (2) a clear cut antigestagenic effect of RU 486 and (3) suggest that both progesterone isoforms are analogously regulated in our culture model. We conclude that human endometrial cell cultures are suitable for the study of the dynamics of steroid receptor expression.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11453036&dopt=Abstract estradiol [PubMed - indexed f
Neuro Endocrinol Lett. 2000;21(1):43-46.
Effects of growth hormone (GH) and growth hormone releasing hormone (GHRH) on progesterone and estradiol release from cultured rat granulosa cells.
Baranowska B, Chmielowska M, Borowiec M, Roguski K, Wasilewska-Dziubinska E.
Neuroendocrinology Department, Medical Centre of Postgraduate Education, Fieldorfa 40, 04-158 Warsaw, Poland. zncmkolbox.com
OBJECTIVES: It has been reported that GHRH-GH-IGF-1 system plays an important role in the regulation of ovarian follicular development and maturation. METHODS: In order to evaluate the direct effects of growth hormone releasing hormone (GHRH) and growth hormone (GH) on steroidogenesis, the effects of GHRH and GH on progesterone and estradiol release from cultured rat granulosa cells were examined. The progesterone and estradiol in supernatants were measured with RIA methods. RESULTS: Our results demonstrated that the addition of GH to the culture medium produced a marked stimulation of progesterone and estradiol. The stimulating effects were observed after administration of GH in all concentrations: 1, 10, 100 nM during 60 and 120 mins of incubation. During 240 mins of incubation the minimal stimulation of progesterone and estradiol was found. However, GHRH administered in 1, 10 and 100 nM did not change progesterone and estradiol release from cultured granulosa cells. CONCLUSION: Growth hormone (GH) but not GHRH has direct stimulating effects on progesterone release from cultured rat granulosa cells.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11455330&dopt=Abstract estradiol [PubMed - as supplied by publisher]
Horm Metab Res. 2001 Jan;33(1):7-9.
Evidence of sex hormone binding globulin binding sites in the medial preoptic area and hypothalamus.
Department of Pharmaceutical Sciences, North Dakota State University, Fargo, USA. Jackic.edu
We have demonstrated a high density of both radiolabeled progesterone and estradiol conjugated to bovine serum albumin binding sites in the medial preoptic area and hypothalamus. Infusions of sex hormone binding globulin into the medial preoptic area of rats increased their female sexual receptivity similarly to the effect of estradiol conjugated to bovine serum albumin, suggesting sex hormone binding globulin acts at binding sites for estradiol conjugated to bovine serum albumin. In this study sex hormone binding globulin was used to displace radiolabeled progesterone conjugated to bovine serum albumin from plasma membrane fractions from the medial preoptic area-anterior hypothalamus and medial basal hypothalamus of ovariectomized rats injected with either 5 microg estradiol benzoate or sesame oil vehicle. We found that sex hormone binding displaced radiolabeled progesterone conjugated to bovine serum albumin in both areas and that in vivo estradiol treatment greatly increased the relative displacement by sex hormone binding globulin in the medial preoptic area-anterior hypothalamus. We interpret these data as indicating the presence of sex hormone binding globulin receptors in brain plasma membranes and further suggest that endogenous steroid conditions may alter these receptors.
Physiol Res. 2002;51(4):407-12.
Sensitivity and specificity of bioassay of estrogenicity on mammary gland and uterus of female mice.
Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic. skardapg.cas.cy
Young intact (18 days of age) and adult ovariectomized (OV-X, ovariectomized between 21 to 24 days of age) C3H/Di mice were used to measure the estrogenicity on the basis of the growth response of mammary epithelial structures and weight of the uterus. The percentage area of the mammary fat pad occupied by mammary epithelial structures was progressively increased by 17beta estradiol from dose 0.001 microg.d(-1). The maximum effective dose of estradiol was 0.01 microg.d(-1) and the dose 10 microg.d(-1) of estradiol decreased mammary size to control levels (inverted-U-shaped dose-response curve). Progesterone alone progressively stimulated mammary growth in young intact females from dose 125 microg.d(-1), in adult OV-X animals from dose 1000 microg.d(-1). Both in young intact and adult OV-X animals, uterine weight progressively increased during estradiol treatment. Progesterone alone had no effect on uterine weight in young intact animals; in adult OV-X animals, uterine weight was increased starting from dose 250 microg.d(-1). Progesterone acted synergistically with estradiol to produce higher mammary growth than that in females treated with estradiol alone. The effects of a combination of estradiol plus progesterone in the mammary gland were mimicked by norethindrone acetate and inhibited by cortisol in both young intact and adult OV-X animals. Testosterone inhibited estradiol plus progesterone stimulated growth of mammary gland only in OV-X animals, but stimulated uterine weights in both young intact and adult OV-X animals. Spleen weight and size of mammary lymph nodes were not affected by estradiol, progesterone, norethindrone acetate or testosterone, but were decreased by cortisol. Cortisol also decreased the pe
Estradiol 1 |
Estradiol 2 |
Estradiol 3 |
Estradiol 4 |
Estradiol 5 |
Estradiol 6 |
Estradiol 7 |
Estradiol 8 |
Estradiol 9 |
Estradiol 10 |
Estradiol 11 |
Estradiol 12 |
Estradiol 13 |
Estradiol 14 |
Estradiol 15 |
Estradiol 16 |
Estradiol 17 |
Estradiol 18 |
Estradiol 19 |
Estradiol 20 |
Estradiol 21 |
Estradiol 22 |
Estradiol 23 |
Estradiol 24 |
Estradiol 25 |
Estradiol 26 |
Estradiol 27 |
Estradiol 28 |
Estradiol 29 |
Estradiol 30 |
Estradiol 31 |
Estradiol 32 |
Estradiol 33 |
Estradiol 34 |
Estradiol 35 |
Estradiol 36 |
Estradiol 37 |
Estradiol 38 |
Estradiol 39 |
Estradiol 40 |
Estradiol 41 |
Estradiol 42 |
Estradiol 43 |
Estradiol 44 |
Estradiol 45 |
Estradiol 46 |
Estradiol 47 |
Estradiol 48 |
Estradiol 49 |
Estradiol 50 |
Estradiol 51 |
Estradiol 52 |
Estradiol 53 |
Estradiol 54 |
Estradiol 55 |
Estradiol 56 |
Estradiol 57 |
Estradiol 58 |
Estradiol 59 |
Estradiol 60 |
Estradiol 61 |
Estradiol 62 |
Estradiol 63 |
Estradiol 64 |
Estradiol 65 |
Estradiol 66 |
Estradiol 67 |
Estradiol 68 |
Estradiol 69 |
Estradiol 70 |
Estradiol 71 |
Estradiol 72 |
Estradiol 73 |
Estradiol 74 |
Estradiol 75 |
Estradiol 76 |
Estradiol 77 |
Estradiol 78 |
Estradiol 79 |
Estradiol 80 |
Estradiol 81 |