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At least 757 records · Page 42Linked to original sources
PubMed1979

Glucocorticoid and estrogen regulation of corticosteroid-binding globulin production by rat liver.

We have recently demonstrated that rat liver can synthesize and secrete corticosteroid-binding globulin (CBG). The present study extends these observations and examines the hormonal regulation of hepatic CBG production. Male rats were pretreated by adrenalectomy and/or glucocorticoid or estrogen administration and the rate of CBG production was measured in vitro. The production rates were assessed by the generation of specific corticosterone binding sites in both a liver-slice preparation and in an isolated perfused liver. The two techniques showed qualitatively similar results. Adrenalectomy enhanced and glucorticoid administration inhibited the rate of CBG production and secretion. Pretreatment of male rats with estradiol stimulated the rate of CBG production. The production rates were 20- to 40-fold higher in the perfused liver demonstrating its superiority over the liver-slice system. The livers from intact rats secreted CBG binding sites at a rate of approximately 18 pmol/g liver per hours, generating an estimated 20% of the total CBG content of a rat each day. The possible clinical implications of the therapeutic use of glucocorticoids that bind to CBG, yet inhibit CBG production, are discussed.

Adrenalectomy↗
PubMed1993

[The pathogenetic basis for using antiestrogens in treating patients with hyperplastic processes of the endometrium in the postmenopause].

Estradiol and progesterone cytosol receptors, tamoxifen relative binding capacity in endometrial tissue samples, serum estradiol and progesterone levels were studied in 60 postmenopausal patients with hyperplastic processes in the endometrium. Estradiol and progesterone receptor levels were increased in glandular cystic polyp tissue, in atypical hyperplastic tissue samples, and in well-differentiated adenocarcinoma tissue. High estradiol levels were detected in the blood sera of patients with glandular cystic polyps, atypical and glandular hyperplasia. Tamoxifen relative binding capacity was the highest in glandular cystic polyps and glandular hyperplasia. Forty patients were treated with 17-hydroxyprogesterone capronate. The data on the status of cytosol receptors and tamoxifen relative binding capacity as well as clinical findings give grounds to include antiestrogens into therapeutic complex for postmenopausal patients with endometrial hyperplasia.

Aged↗
PubMedDate not supplied

[Aromatase inhibitors--theoretical concept and present experiences in the treatment of endometriosis].

The medical treatment of endometriosis needs to be optimized. Therapeutic management strategies of endometriosis-associated pain or recurrent disease is primarily aimed at downregulating the ovarian function or at antagonizing the effect of estrogen in ectopic endometrial implants. In this context, basic research is delivering powerful tools for the possible development of new, specific treatment modalities. Recently, aromatase overexpression has been detected in endometriotic tissue. Aromatase (p450arom) is responsible for conversion of C19 androgens to estrogen in several human tissues. Aromatase activity gives rise to local estrogen biosynthesis, which, in turn, stimulates prostaglandin E(2) production by upregulation of cyclooxygenase-2 (COX-2), thus establishing a positive feedback cycle. Another abnormality in endometriosis, i. e. the deficiency in 17 beta-hydroxysteroiddehydrogenase type-II (17 beta-HSD-Type-II) expression, impairs the inactivation of estradiol to estrone. In contrast to the eutopic endometrium, these molecular aberrations collectively favour accumulation of increasing amounts of local estradiol and prostaglandin E(2) in endometriosis. In several human cell lines, prostaglandin and estrogen concentrations are associated with proliferation, migration, angiogenesis, apoptosis resistance, and even invasiveness. Consequently, aromatase and COX-2 are promising new therapeutic targets. In summary, specific aromatase inhibitors (such as Letrozole, Anastrozol or Exemestan) or selective COX-2 inhibitors (e.g. Celecoxib, Rofecoxib) are of great interest to be studied in clinical trials in premenopausal woman with endometriosis to extend the spectrum of currently available treatment options.

Aromatase↗
PubMed1995

Dehydroepiandrosterone reduces progressive dermal ischemia caused by thermal injury.

Progressive ischemia and necrosis of the skin following thermal injury are reduced by postburn administration of the steroid hormone dehydroepiandrosterone (DHEA). Thermally injured animals were provided with a subcutaneous injection of DHEA, or a related species of steroid hormone, at various times after burning. During the 96 hr following administration of the scald burn, tissue necrosis was closely monitored. Subcutaneous administration of DHEA at approximately 1 mg/kg/day achieved optimal protection against the development of progressive dermal ischemia. DHEA, 17 alpha-hydroxy-pregnenelone, 16 alpha-bromo-DHEA, and androstenediol each demonstrated, a similar level of protection. Other forms of steroids, including DHEA sulfate, androstenedione, 17 beta-estradiol, or dihydrotestosterone, exhibited no protective effect under the conditions tested. Additionally, intervention therapy with DHEA could be initiated up to 4 hr, but not 6 hr, after burn without a marked reduction in therapeutic benefit. Examination of the microvasculature of thermally injured dorsal skin suggested that postburn intervention with DHEA, either directly or indirectly, maintained a normal architecture in most of the dermal capillaries and venules within burn-exposed tissue. These findings suggest that systemic intervention therapy of burn patients with DHEA or a similar acting steroid hormone may be useful in preventing the progressive tissue destruction caused by progressive ischemia.

17-alpha-Hydroxypregnenolone↗
PubMed2001

17-beta-estradiol suppresses IL-2 and IL-2 receptor.

Interleukin-2 (IL-2) plays an important role in adaptive immune responses. These responses differ between females and males and may be due to the sex steroid estrogen. In this investigation we show that estrogen suppresses IL-2 production from activated peripheral blood T cells and CD4+ T cell lines at the transcriptional level. Suppression of IL-2 occurred at short term, high 17-beta-estradiol concentrations as well as longer term lower 17-beta-estradiol concentrations. In CD4+ Jurkat T cells, suppression of IL-2 was associated with decreased nuclear binding of two important IL-2 promoter transcription factors: NFkappaB and AP-1. The decreased nuclear binding of NFkappaB occurred in the setting of estrogen-induced increases in IkappaBalpha protein levels, an important inhibitor of NFkappaB nuclear translocation. 17-beta-Estradiol was also shown to inhibit IL-2 receptor (IL-2R) expression in activated peripheral blood T cells. Estrogen-induced suppression of IL-2 and its receptor may have many ramifications for our understanding of immune and autoimmune sexual dichotomies, immune responses during pregnancy, and potential therapeutic intervention with hormone agonists and antagonists.

Active Transport, Cell Nucleus↗
PubMed1994

Dysfunctional uterine bleeding (DUB).

Cyclic or irregular uterine bleeding is common in perimenarchal and perimenopausal women with or without endometrial hyperplasia. The disturbance often requires surgical treatment because of its negative effects on both blood loss and abnormal endometrial growth including the development of endometrial cancer. The endometrium is often overstimulated during the perimenopausal period when estrogen/progesterone production is unbalanced. A therapeutical approach with gonadotropin-releasing hormone agonist (GnRHa) was proposed in a depot formulation (Zoladex) that induces a sustained and reversible ovarian suppression. To avoid the risk of osteoporosis and to obtain adequate endometrial proliferation and differentiation during ovarian suppression, transdermal 17-beta-estradiol and oral progestin were administered. Results of 20 cases versus 20 controls showed a reduction of metrorrhagia, a normalization of hemoglobin plasma concentration, and an adequate proliferation and secretory differentiation of the endometrium of patients with abnormal endometrial growth. Abnormal uterine bleeding is mainly due to uterine fibrosis and an inadequate estrogen and/or progesterone production or to a disordered estrogen transport from blood into the endometrium. In premenopausal women, endometrial hyperplasia may be part of a continuum that is ultimately manifested in the histological and biological pattern of endometrial carcinoma. The regression of endometrial hyperplasia obtained by using the therapeutic regimen mentioned above represents a preventive measure for endometrial cancer. Finally the normalization of blood loss offers a good medical alternative to surgery for patients with DUB.

Adult↗
PubMed1981

Effect of ampicillin or amoxycillin administration on plasma and urinary estrogen levels during normal pregnancy.

Urinary estrogen excretion and plasma levels of conjugated and unconjugated 17 beta-estradiol and estriol were measured in 10 healthy, pregnant women before, during and after a 5-day course of orally administered ampicillin (2 g/day) or the same dose of amoxycillin. On the second and third day of ampicillin treatment the plasma level of conjugated estriol and the urinary estrogen level were lower than pretreatment values, but then returned to basal values despite continuing treatment. Plasma concentrations of conjugated and unconjugated 17 beta-estradiol and of unconjugated estriol did not show any significant change during treatment. Hormone changes in women on amoxycillin were qualitatively similar to but smaller and less consistent than those induced by ampicillin. The results indicate (1) that the use of amoxycillin instead of ampicillin in pregnancies that require estrogen monitoring of feto-placental function, has little clinical advantage, and (2) that the adverse effect of therapeutic doses of ampicillin (and amoxycillin) on estrogen levels during pregnancy may be less important than is commonly assumed.

Amoxicillin↗
PubMedDate not supplied

Effects of toremifene and its main metabolites on growth of breast cancer cell lines.

The effects of toremifene, an antiestrogen, and its two main metabolites (4-hydroxy- and N-desmethyltoremifene) on cell proliferation have been tested in a series of breast cancer cell lines, with positive (MCF7, ZR 75.1, T47D, 734B) or negative steroid receptor status (MDA-MB 231, BT20). Drug effects were evaluated at concentrations similar to those obtained in breast cancer patients on toremifene treatment, and in the presence or absence of estradiol. Results showed that, for both positive and negative cell lines, high concentrations of the antiestrogens (10(-6)M) were inhibitory, while lower doses (10(-7)M, 10(-8)M) were stimulatory. These data confirm the biphasic behaviour of toremifene and its derivatives. In terms of a clinical application of toremifene, these results seem to suggest that while high doses of toremifene and its derivatives might be therapeutic, lower concentrations might stimulate cell growth and enhance tumor progression.

Antineoplastic Agents↗
PubMed1993

Bioequivalence of a 17 beta-estradiol hydroxypropyl-beta-cyclodextrin complex in postmenopausal women.

Five postmenopausal women received single doses of a 0.675 mg estradiol hydroxypropyl-beta-cyclodextrin (estradiol-HP beta CD) sublingual tablet by the sublingual and oral route. A single dose of a 1 mg micronized estradiol tablet was given orally for comparison. Blood samples were obtained over 48 hours for measurement of estradiol, estrone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Sublingual administration produced faster and significantly higher peak estradiol concentrations than after oral administration of either estradiol-HP beta CD or micronized estradiol. The concentration-time area under the curve of estradiol after sublingual estradiol-HP beta CD was also significantly larger than after oral administration of either estradiol-HP beta CD or micronized estradiol, reflecting a larger estradiol bioavailability. The estradiol/estrone concentration ratio after sublingual estradiol-HP beta CD revealed a predominance of estradiol for the first 2 hours after the dose, followed by an estrone predominance. Both oral doses produced a predominant delivery of estrone to the systemic circulation. There was not difference in time-averaged LH suppression between the three phases. However, estradiol-HP beta CD sublingually produced greater FSH suppression than oral micronized estradiol.

Administration, Sublingual↗
PubMed2003

Comparative bioequivalence studies with Estradot and Menorest transdermal systems.

OBJECTIVES: To compare the relative bioavailability of Estradot, a small size, new generation estradiol transdermal system (ETS) to Menorest, in healthy postmenopausal women. METHODS: In two open-label, single center, randomized, crossover, bioequivalence studies, healthy postmenopausal women aged 40-65 years received treatment with all the test regimens. In Study 1 (single-dose study), patients wore 5 cm(2) (50 microg/day), 10 cm(2) (100 microg/day) Estradot and 29 cm(2) (100 microg/day) Menorest for 84 h. In Study 2 (multiple-dose study), patients wore a regimen of four consecutive treatments with a 5 cm(2) (50 microg/day) new generation patch, Estradot and a 14.5 cm(2) (50 microg/day) patch, Menorest. Blood samples were drawn at various time-points in both studies. Estradiol and estrone serum levels were determined by gas chromatography/mass spectrometry or radioimmunoassay methods. Skin irritation (erythema and edema), patch adherence and local skin reaction were assessed following patch removal. RESULTS: In Study 1, baseline-uncorrected C(max) for estradiol for Estradot 50 and 100 microg/day and Menorest 100 microg/day was 54.8, 106.2 and 101.6 pg/ml, respectively, and C(max) for estrone was 75.6, 97.0 and 98.3 pg/ml, respectively. In Study 2, the baseline-uncorrected mean maximum serum concentration (C(max)) for estradiol for Estradot 50 microg/day and Menorest 50 microg/day patches was 56.7 and 52.7 pg/ml, respectively, and C(max) for estrone was 41.7 and 41.3 pg/ml, respectively. No significant skin irritation was observed in either study, but Estradot caused less skin irritation than Menorest. CONCLUSIONS: Estradot produced comparable serum concentrations of estradiol and estrone and caused less skin irritation than Menorest.

Administration, Cutaneous↗
PubMed1999

Does the antimigraine action of flunarizine involve the dopaminergic system? A clinical-neuroendocrinological study.

We have investigated the prolactin response to bromocriptine (BRC), a D2 dopamine receptor agonist in migrainous women before and after treatment with flunarizine. We evaluated whether this test was predictive of therapeutic efficacy of flunarizine treatment and whether the therapeutic response to flunarizine treatment was related to its effect on dopaminergic system at tuberoinfundibular level. Ten migrainous women underwent a BRC test in the late follicular phase before and after 1 and 3 months of treatment with flunarizine 10 mg at bedtime. Blood samples of prolactin (PRL), growth hormone, follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were taken at basal condition. PRL was also evaluated 1 and 2 h after BRC (2.5 mg) administration. Each patient kept a daily headache diary for 1 month prior to the test and throughout the study. The level of PRL inhibition after BRC administration, observed before flunarizine treatment, was not predictive of the therapeutic response observed after 1 and 3 months of treatment. The effect of flunarizine on PRL level was not related to the therapeutic efficacy of the drug. These data suggest that flunarizine does not attenuate the activity of dopaminergic neurons in migrainous patients, and that the antimigraine effect of flunarizine does not seem related to its action on dopaminergic system at least at tuberoinfundibular level.

Adult↗
PubMed1998

[Relationship between sex hormone levels and blood lipids/immunity in perimenopausal women].

To investigate the relationship between sex hormone levels and blood lipids/immunity and to evaluate the therapeutical effects of nylestriol, 96 women without coronary heart disease(CHD) were studied during their perimenopausal period. The estimation of serum biochemical components included serum 17 beta-estradiol(E2), testosterone(T), total cholesterol(TC), triglyceride (TC), high density lipoprotein cholesterol(HDL-C), low density protein cholesterol(LDL-C), apolipoprotein A-I(ApoAI), apolipoprotein B(ApoB), lipoprotein (a)[Lp(a)], immunoglobulin G(IgG), and IgG antibody against cardiolipin(ACAIgG). Thirty-six postmenopausal volunteers were divided into two groups and randomized to treat with either 2 mg nylestriol or placebo. In postmenopausal women, serum levels of E2, E2/T, HDL, and ApoAI decreased, while those of T, TC, TG, LDL, ApoB, Lp(a), IgG, and ACAIgG increased. Serum level of E2 was positively correlated to HDL-C and negatively correlated to TC, ApoB, LDL, IgG, and ACAIgG. Serum level of T was positively correlated to LDL, IgG, and ACAIgG and negatively correlated to HDL. In the nylestriol group, as compared with the results before treatment, serum levels of TG, TC, LDL, IgG, and ACAIgG decreased and that of HDL-C increased after treatment. We conclude that estradiol is a protective factor of CHD, whereas testerone is a dangerous factor. After menopause, the imbalance of the estradiol/testosterone ratio increases the incidence of CHD. Nylestriol is an effective substitute for estradiol to prevent CHD in post menopausal women.

Cholesterol↗
PubMed1988

Effect of exogenous ovarian steroids on the uterine luminal prostaglandins in ovariectomised mares with experimental endometritis.

Prostaglandins (PGs) F and E2 were measured in lavage fluid from the uterus of ovariectomised mares after experimental induction of uterine inflammation. Treatment with progesterone alone, or progesterone followed by oestradiol, significantly increased the concentrations of these PGs in the lavage compared with mares treated with oestradiol or control mares. Ovarian steroids, therefore, influenced uterine PG synthesis in response to an inflammatory stimulus. To determine whether the uterine lavage procedure might contribute to the concentrations of prostaglandins in the lavage, the procedure was also performed on six intact mares. With the exception of washings obtained at luteolysis, uterine concentrations of PGF (measured as the plasma metabolite 15-keto-13,14-dihydro PGF2 alpha) had returned to prewashing levels within 30 minutes of the start of uterine lavage. Lavage was therefore unlikely to have influenced the concentrations of prostaglandins in the lavage fluid.

Animals↗
PubMed1985

Growth inhibition and increase of insulin receptors in antiestrogen-resistant T47DCO human breast cancer cells by progestins: implications for endocrine therapies.

There is renewed interest in the use of progestins to treat advanced breast cancer because results with these agents are comparable to those obtained with antiestrogens. However, it is not known whether progestins inhibit the growth of breast tumor cells directly and independently of estradiol. To study this, we have used T47DCO human breast cancer cells. The progesterone receptors in these cells do not require estrogen induction, and this permits study of pure progestin effects without interference by estradiol. We report here that, in the absence of estradiol, physiological concentrations of progestins directly inhibit proliferation of these cells. At the same time, progestins increase the levels of the receptors for insulin, a common cell mitogen. Ten days of treatment with 1 or 10 nM of the synthetic progestin R5020 suppresses cell growth approximately 50 to 60%. This is consistent with the concentrations that either partially (approximately 10%) or more extensively (greater than 60%) translocate cytoplasmic progesterone receptors. Even a brief 1-hr pulse of R5020 has long-term growth-inhibitory effects. Progesterone is also antiproliferative, but its effects are attenuated because, unlike R5020, it is rapidly metabolized in the medium. Other synthetic progestins also inhibit cell growth, but unrelated steroids (estradiol, androgens, glucocorticoids, 1,25-dihydroxyvitamin D3) are ineffective. While growth is suppressed by R5020, insulin receptors increase rapidly and then fall to a new, elevated steady state as the cells slowly begin to proliferate. Only progestins have this effect on insulin receptors. We conclude that the hormonal regulation of breast tumor cell growth is complex and includes progestins among the regulating factors. Furthermore, since T47Dco cells are antiestrogen-resistant and estrogen receptor-negative, the antiproliferative effects of progestins must be mediated through mechanisms that differ from the cytotoxic effects of antiestrogens. We propose that, clinically, antiestrogens and progestins may have complementary uses in breast cancer treatment, and we outline two therapeutic strategies.

17-alpha-Hydroxyprogesterone↗