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PubMed2004

Beneficial Effects of Estrogens on Indices of Renal Damage in Uninephrectomized SHRsp Rats.

Renal diseases tend to be less severe among premenopausal female patients, compared with male patients. Experimental data on the effects of estrogens on renal damage are controversial, and potential underlying mechanisms have not been fully clarified. Three-month-old, female, uninephrectomized (UNX), sham-operated or ovariectomized (OVX) SHRsp rats were left untreated or received either 17beta-estradiol 3-benzoate (25 micro g/d) or estriol (0.02 mg/d) daily. After 3 mo, indices of renal damage (glomerulosclerosis index and tubulointerstitial damage index) and glomerular geometric parameters were investigated. The expression of desmin, TGF-beta, endothelin-1, collagen IV, endothelial nitric oxide synthase, and estrogen receptors alpha and beta in the glomeruli and tubulointerstitium was immunohistochemically evaluated. Estradiol and estriol did not significantly affect kidney weights or BP. Estradiol and estriol caused significant reductions in albuminuria (vehicle-treated UNX/OVX animals, 25.4 +/- 8.52 mg/24 h; estradiol-treated UNX/OVX animals, 15.37 +/- 6.12 mg/24 h; estriol-treated UNX/OVX animals, 6.54 +/- 2.24 mg/24 h). The glomerulosclerosis index was significantly lower in estriol- and estradiol-treated animals (estradiol-treated UNX/OVX animals, 0.69 +/- 0.16; estriol-treated UNX/OVX animals, 0.21 +/- 0.12; P < 0.05), compared with vehicle-treated animals (1.46 +/- 0.09); the tubulointerstitial damage index exhibited a similar pattern. The mean glomerular volume was significantly less in estrogen-treated animals. UNX/OVX animals demonstrated significantly greater expression of TGF-beta and endothelin-1 in immunohistochemical, in situ hybridization, and reverse transcription-PCR assays. This increase was abrogated by estriol but not estradiol. Similarly, significantly higher glomerular and tubulointerstitial expression of proliferating cell nuclear antigen and collagen IV was observed in UNX/OVX animals, and expression was decreased by estriol but not estradiol. It was concluded that, in the UNX model of spontaneous renal damage, glomerular lesions and glomerular hypertrophy were reduced by estriol but less consistently by estradiol. In parallel, loss of podocytes, evidence of podocyte injury (i.e., desmin expression), and expression of mediator systems of glomerular damage were decreased, pointing to a major renoprotective action of estriol.

Animals↗
PubMed2004

Topical estrogen protects against SIV vaginal transmission without evidence of systemic effect.

BACKGROUND: Accumulating data suggest that the state of the vaginal epithelium affects a woman's risk of HIV vaginal transmission and several human and non-human primate studies have shown that the rate of HIV or SIV vaginal transmission is decreased when estrogen is dominant. Systemic estrogen can protect against SIV vaginal transmission. OBJECTIVE: To determine the safety and efficacy of topical estrogen in preventing SIV vaginal transmission. DESIGN: The non-human primate model of HIV vaginal transmission was used to assess vaginal estriol cream in ovariectomized macaques. METHODS: Twelve macaques were treated intravaginally with estriol and eight with placebo cream twice a week. The vaginal and systemic effects of estriol were determined by colposcopy and serum luteinizing hormone, levels of which would decline in the presence of systemic estrogen. After 5 weeks of therapy, the animals were challenged vaginally with pathogenic SIVmac251. RESULTS: Vaginal estriol resulted in minimal serum estriol levels and had no effect on serum luteinizing hormone levels. Vaginal epithelia cornified and thickened significantly in response to estriol therapy. One of the estriol-treated animals became infected after this single challenge, while six of the control animals became infected (P = 0.0044). CONCLUSIONS: These data demonstrate that topical vaginal estriol can strongly protect against SIV vaginal transmission, while having no detectable systemic effect. These results support the study of topical vaginal estriol in preventing HIV vaginal transmission in at-risk women.

Administration, Topical↗
PubMed1986

[Clinical significance of the feto-placental unit during pregnancy and parturition].

Theoretical basis of measurement of estriol during pregnancy. It was clarified that the feto (adrenal and liver)-placental unit plays an important role in the biosynthesis of estriol during pregnancy. The theoretical basis of the usefulness of estriol estimation in maternal urine as the indicator of fetal viability is therefore established, and a simplified estriol assay (LAIR-3 minutes method) was developed. As to the steroid values in the amniotic fluid during pregnancy, high level of progesterone (P4) in the first trimester and prominent rises of DHA-S and estriol values near term were shown. Furthermore, transference of amniotic DHA-S to the mother through the amniotic membrane was demonstrated by the in vivo study using deuterium labeled DHA-S given in the amniotic fluid. In vivo study using deuterated pregnenolone sulfate (P5-S) given in the maternal circulation demonstrated that maternal P5-S was partially used as the precursor of placental P4. Therefore, it is suggested that the precursor of placental P4 is mainly derived from the feto-placental side rather than the maternal one. Changes of steroidal environment near term. Steroid hormone assay by gas chromatography mass-spectrometry using deuterium labeled compound as internal standard was developed, and (fetal adrenal) steroid values in maternal blood were measured. DHA-S, 16 alpha-OH- DHA-S and estriol values increase in the prepain and labor period and P4 and 20 alpha-OH-P4 values decrease during labor. In vivo study using deuterium labeled DHA-S given to the fetal side in the perinatal period demonstrated that DHA-S originated from fetal adrenal transferred to the mother through placenta without being subjected to the aromatisation. The elevation of uterine sensitivity to oxytocin in the perinatal period is closely related to both the increases of DHA-S and estriol levels, and the decrease of P4 values in the maternal blood. As to the hormonal factors of hypothalamo-posterior pituitary system, the levels of estrogen stimulated neurophysin (ESN) and oxytocin in the maternal blood elevated parallel with the increase of estrogen level in the prepain period. The administration of DHA-S (100mg, twice a week) in the perinatal period accelerate the maturation of uterine cervix with concomitant augmentation of DHA-S concentration and increased proline hydroxylase activity in the cervical tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Chorionic Gonadotropin↗
PubMed1977

Estrogen metabolism in nonhuman primates. I. In vitro biosynthesis of estrogen glucosiduronates in rhesus monkey liver.

Estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate and estriol-16alpha-glucosiduronate have been biosynthesized in substantial yield by incubation of radioactive estrone, 17beta-estradiol, estriol and uridine diphosphoglucosiduronic acid with rhesus monkey liver homogenates. The metabolites were characterized by chromatography on Celite and DEAE-Sephadex, enzyme hydrolysis, derivative formation and crystallization to constant specific activity. The percent conversion to 17beta-estradiol-17-glucosiduronate from 17beta-estradiol ranged between 56-71%; from estrone, the conversion was 49-54%. Other metabolites formed from estradiol were estrone glucosiduronate (12-21%) and 17beta-estradiol-3-glucosiduronate(5-12%). The same metabolites derived from estrone accounted for 18-28% and 10-14% respectively. After estriol incubation, more than 90% of the steroid was converted to estriol-16alpha-glucosiduronate with no detectable estriol-3-glucosiduronate. This report represents the first time that 17beta-estradiol-17-glucosiduronate has been reported as a metabolite in the rhesus monkey and this is the only known species which forms 17beta-estradiol-17-glucosiduronate as the predominant metabolite of either estrone or estradiol in vitro. Rhesus monkey liver is similar to the human and baboon in that it metabolizes estriol exclusively to estriol-16-glucosiduronate.

Animals↗