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PubMed1987

Reactivation of regressing corpora lutea by estradiol in the pregnant rat: dependence on placental lactogen.

Previous investigations have clearly demonstrated that estradiol maintains corpus luteum function. However, it is unknown whether estradiol can restimulate progesterone synthesis and/or growth of corpora lutea that have already undergone luteolysis. The present study was designed to determine 1) whether estradiol can reactivate the steroidogenic capacity and/or growth of corpora lutea that are deprived of luteotropic support, 2) whether estradiol affects progesterone metabolism, and 3) whether the action of estradiol is related to levels of rat placental lactogen in the peripheral circulation. Rats were hypophysectomized and hysterectomized on Day 12 of pregnancy and were treated between Days 12 and 15 with either estradiol (100 micrograms/day) or 1-cm testosterone implants. Both treatments are known to maintain luteal concentrations of estradiol at physiological levels. In vivo treatment with either estradiol or testosterone prevented the drop in progesterone production and maintained the concentration of serum progesterone at levels found in intact pregnant rats. This action was not due to an alteration in the rate of metabolism of progesterone to 20 alpha-hydroxyprogesterone, since peripheral serum levels and in vitro production of 20 alpha-hydroxyprogesterone were unaffected by estradiol. When testosterone treatment was started 24 and 48 h after hypophysectomy and hysterectomy, at a time when progesterone production had been markedly reduced and luteal growth had ceased, a restimulation of both progesterone synthesis and luteal growth was observed. However, in all cases the ability of estradiol to stimulate progesterone was finite, and corpora lutea ceased to respond by Day 17, coincident with the time that rat placental lactogen became undetectable in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Seasonal changes in gonadotropin-releasing hormone secretion in the ewe: alteration in response to the negative feedback action of estradiol.

Two experiments were performed to test the hypothesis that there is a seasonal change in the negative feedback effect of estradiol on episodic secretion of GnRH in the ewe. The first experiment identified a specific estradiol treatment (delivered by s.c. Silastic implant) that produced a 50% decrease in the frequency of pulsatile secretion of LH in ovariectomized ewes during the anestrous season. In the second experiment, this estradiol treatment was administered to ovariectomized ewes during the mid-breeding and anestrous seasons. Separate groups of ovariectomized ewes not treated with estradiol were included during each season to test for a seasonal difference in the effect of estradiol on episodic GnRH and LH secretion. Samples of hypophyseal portal blood (for GnRH) and jugular blood (for LH) were obtained at 5-min intervals approximately one month after placement of the estradiol implants. During the breeding season, no effect of estradiol was observed on either the frequency or size of GnRH and LH pulses. During anestrus, however, estradiol produced a profound suppression of the frequency of GnRH and LH pulses, and an increase in GnRH pulse size. No significant seasonal change was observed in the characteristics of GnRH and LH pulses in ovariectomized ewes in the absence of estradiol treatment. These findings lead to the conclusion that there is a marked seasonal change in the negative feedback effect of estradiol on episodic GnRH secretion in the ewe, with the steroid being maximally effective during anestrus.

Anestrus↗
PubMed1997

Immunoneutralization of transforming growth factor alpha present in bovine follicular fluid prevents the suppression of the follicle-stimulating hormone-induced production of estradiol by bovine granulosa cells cultured in vitro.

Growth factors such as transforming growth factors alpha (TGF alpha) and beta (TGFbeta) secreted by theca cells and present in bovine follicular fluid (bFF) have been implicated in granulosa cell growth and differentiation. We investigated these phenomena using two complementary approaches to evaluate the physiological contribution of TGF alpha and TGFbeta in the control of the FSH-induced estradiol production in bovine granulosa cells from large follicles. Granulosa cells (3 x 10(5) viable cells/cm2) harvested from eCG-treated prepubertal calves were cultured (serum free) in wells containing 500 microl/cm2 of defined Ham's F-12 medium supplemented with 0.5 ng/ml FSH for the first 3 days (37 degrees C; 95% air:5% CO2). In the first approach, the effects of individual addition of TGF alpha and TGFbeta at final concentrations of 1 x 10(-4) to 10 ng/ml were determined on Day 4 of culture after stimulation of granulosa cell estradiol production with 6 ng/ml FSH. In a second approach, TGF alpha or TGFbeta was removed specifically from bFF (from large follicles > 10 mm) by immunoneutralization. Thereafter, effects of immunoneutralization of TGF alpha or TGFbeta (0, 0.1, 1, 10, and 100 microg/ml anti-TGF neutralizing antibody) present in bFF (2%) were determined on Day 4 of culture following stimulation of granulosa cell estradiol production with 6 ng/ml FSH. On Day 4, FSH increased (p < 0.001) granulosa cell estradiol production (0 vs. 6 ng/ml FSH). Addition of TGF alpha decreased the granulosa cell estradiol production after 6 ng/ml FSH stimulation in a dose-dependent manner (p < 0.001). In contrast, addition of TGFbeta had no effect on the granulosa cell estradiol production (p > 0.1) after the addition of 6 ng/ml FSH. Addition of bFF (2%) decreased (p < 0.0001) the FSH-induced estradiol production by bovine granulosa cells. After immunoneutralization of TGF alpha in bFF, however, this suppressed FSH-induced estradiol production was restored to levels obtained in the absence of bFF, and this occurred in a dose-dependent manner (p < 0.05). Immunoneutralization of TGFbeta in bFF did not prevent (p > 0.1) the suppressive effect of bFF on FSH-induced estradiol production. These results suggest that TGF alpha produced in vivo by large bovine follicles can act locally (auto/paracrine manner) to suppress granulosa cell estradiol production.

Animals↗
PubMed1998

Estradiol increases relative amounts of insulin-like growth factor binding protein (IGFBP)-3 in serum and expression of IGFBP-2 in anterior pituitaries of ewes.

This study determined whether estradiol regulates insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBPs) in the pituitary gland, hypophyseal stalk median eminence (SME), and circulation concomitantly with effects on LH. Ovariectomized ewes received an estradiol implant or no implant during the anestrous season and were slaughtered 80 days later. Estradiol suppressed serum LH to a greater extent during anestrus than after onset of the breeding season (Days 60 and 75). Amounts of mRNA for LHbeta subunit were decreased by estradiol, but mRNA for alpha and FSHbeta subunits were not affected. Estradiol increased serum IGF-I, IGFBP-3, and IGFBP-4 throughout the treatment period, but it did not influence other IGFBPs in serum. In response to estradiol, pituitary IGFBP-2 tended to increase and mRNA for IGFBP-2 increased twofold. Other IGFBPs in the pituitary gland were not influenced by estradiol. In the SME, IGFBP-2, IGFBP-5, and the 40-kDa IGFBP-3 were increased by estradiol. Thus, estradiol influences both the IGF and gonadotropin systems in sheep. Estradiol influences on gonadotroph function may be mediated by alterations in the IGF system.

Animals↗
PubMed2000

Estradiol-17beta inhibits nitric oxide synthase (NOS)-II and stimulates NOS-III gene expression in the rat uterus.

Nitric oxide (NO) is synthesized by NO synthases (NOS) from L-arginine in a variety of tissues, including rat uterus. Progesterone was shown to be required for maintaining elevated NOS II expression in pregnant rat uterus. However, effects of estrogens on uterine NOS II expression remains unclear. In the present study, we examined whether 17beta-estradiol regulates NO production and NOS II expression in the rat uterus during pregnancy and in nonpregnant rats treated with lipopolysaccharide (LPS). Rats on Day 18 of pregnancy received 17beta-estradiol (0.5 or 5 microgram/rat). Groups of ovariectomized (ovx) rats received 17beta-estradiol (5 microgram/rat) or LPS (1 mg/rat) or a combination of the two or received vehicle only. All rats were sacrificed 24 h after treatments. Nitrite concentrations in uterine cultures were measured by Greiss reaction. Uterine NOS II and NOS III proteins and mRNA levels were determined by Western blotting and reverse transcription polymerase chain reaction, respectively. In the pregnant rat, estradiol administration caused inhibition in total NO production, suppression of both mRNA and protein levels of NOS II enzyme, and increase in NOS III mRNA and protein levels in the uterus in a dose-dependent manner. The data indicate that estradiol inhibits NOS II and total NO generation and stimulates NOS III expression. In ovx rats, LPS stimulated NOS II mRNA and NO production by the uterus. Coadministration of 5 microgram estradiol profoundly suppressed NOS II mRNA and NO generation but elevated NOS III mRNA. Thus, estradiol inhibited LPS-induced increases in NOS II mRNA. Estradiol inhibits NO production by NOS II through the inhibition of NOS II expression in the rat uterus. This inhibition of NOS II expression occurs whether NOS II expression is constitutive (pregnancy) or induced (LPS-treated nonpregnant). Estradiol inhibition of NOS II expression occurs in the presence (pregnancy) or absence (ovx) of progesterone. Estradiol may play a role in regulating NOS II expression and NO production and uterine contractility during pregnancy and labor.

Animals↗
PubMed2001

Estradiol-17beta is produced in bovine corpus luteum.

The aim of this study was to investigate the expression of cytochrome P450 aromatase (aromatase) mRNA, its activity, and estradiol-17beta (estradiol) secretion in bovine corpus luteum (CL) during the estrous cycle. Expression of aromatase mRNA was examined in CL at the early, mid, late, and regressed luteal stages by using a reverse transcription-polymerase chain reaction. Aromatase mRNA was detected in all luteal stages examined, although aromatase expression was significantly lower during the early and regressed luteal phases compared to the mid and late luteal phases. Moreover, cultured midluteal cells clearly converted exogenous [(3)H]androstenedione into estradiol, and an aromatase inhibitor significantly inhibited this conversion. To characterize the local release of estradiol within the CL during the estrous cycle, an in vitro microdialysis system (MDS) of CL was conducted. Estradiol in MDS perfusate was confirmed by a reverse-phase high-performance liquid chromatography in combination with enzyme immunoassays. Basal release of estradiol from microdialyzed CL did not change during the estrous cycle. Additionally, when freshly prepared midluteal cells were exposed to estradiol (10(-14) to 10(-9) M), estradiol stimulated prostaglandin (PG) F(2alpha) secretion (P < 0.05), although it did not affect progesterone and oxytocin secretion. The overall results indicate that estradiol is produced locally in bovine CL throughout the estrous cycle, and they suggest that estradiol plays a role in regulating PGF(2alpha) production in CL as an autocrine/paracrine factor.

Androstenedione↗
PubMed1995

Effect of estradiol 17 beta on pressor responses of rat mesenteric bed to norepinephrine, K+, and U-46619.

We reinvestigated the effect of estradiol 17 beta on the responses of adrenergic and nonadrenergic vasoconstrictors characterized it in terms of steroid specificity, time course, and the role of classic estrogen receptors. We evaluated the effect of estradiol 17 beta on the pressor responses of isolated perfused rat mesenteric vascular bed (McGregor's preparation). Estradiol 17 beta (7-700 nM) significantly increased the pressor response to bolus applications of norepinephrine (NE) (p < 0.05). However, estradiol 17 beta did not significantly increase the responses to endogenous NE release induced by electrical field stimulation. Other steroids, testosterone, and the 17 alpha isomer of estradiol (7 and 700 nM) were ineffective. Estradiol 17 beta (700 nM) also significantly increased the maximum pressor response of rat mesenteric preparation to both the prostaglandin endoperoxide analogue U-46619 and to K+. The potentiation by estradiol 17 beta of mesenteric vasoconstriction elicited by NE, K+, and U-46619 was rapid (2-8 min), suggesting that a nuclear receptor may not be involved. This notion received further support in that significant potentiation of the NE-induced pressor response was also observed with estradiol 17 beta conjugated to albumin (700 nM), but not when electrical field stimulation was used. The conjugate increased the effect of all NE concentrations. Its effect was also more consistent (p < 0.01) than that elicited by free estradiol 17 beta. The dose-response curve was shifted to the left, and the maximum effect was increased. These data suggest that estradiol 17 beta may possess rapid nongenomic actions unrelated to nuclear receptor binding and gene transcription.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Beta-estradiol acutely potentiates the depression of cardiac excitability by lidocaine and bupivacaine.

Pregnancy is known to increase myocardial susceptibility to bupivacaine-induced cardiovascular collapse, and prolonged pretreatment of rabbits with high doses of progesterone potentiates bupivacaine's depression of the maximal rate of increase (Vmax) of the cardiac action potential. Short-term effects of progesterone are not detected in vitro, but other steroids elevated during pregnancy might be acutely active in this model. These experiments tested whether acute exposure to beta-estradiol potentiates local anesthetic/antiarrhythmic depression of Vmax and conduction velocity in rabbit cardiac tissue in vitro. Standard intracellular microelectrodes were used to measure electrophysiologic changes produced by beta-estradiol, local anesthetics, or both in dissected segments of heart containing the Purkinje fiber and ventricular muscle cells from ovariectomized rabbits. In tissues preincubated in beta-estradiol (3.3 nM), addition of bupivacaine (10.4 microM), or lidocaine (85.4 and 129 microM) decreased Vmax significantly more than in steroid-free Tyrode's (p<0.001). Alone, beta-estradiol had no effect on Vmax and depression of Vmax by the nonanesthetic Na+ channel blocker tetrodotoxin (TTX, 3 microM) was not potentiated by beta-estradiol. In preparations initially exposed to bupivacaine for 30 min, subsequent addition of beta-estradiol decreased Vmax further within 10 min (p<0.05). Bupivacaine's greater depression of Vmax at higher frequencies (3 Hz) was exaggerated by beta-estradiol. However, the rate-dependent slowing of conduction by bupivacaine was lessened or even reversed by beta-estradiol addition. Such rapid physiologic changes cannot be due to genomic actions by the hormone that take hours to manifest. Nor is the potentiation due to a general decrease in membrane excitability because the comparable inhibition by TTX is insensitive to estradiol. Because beta-estradiol potentiates the inhibition of myocardial excitability, but alleviates the slowing of impulse conduction between the Purkinje fiber and ventricular muscle produced by local anesthetics, the hormone must produce changes in more than one ionic conductance. Both pregnancy and conditions that abnormally alter levels of steroid hormones have ramifications for local anesthetic-induced cardiotoxicity and antiarrhythmic pharmacotherapeutics.

Action Potentials↗
PubMed1998

Estradiol 17-beta represses insulin-like growth factor I receptor expression in smooth muscle cells from rabbit cardiac recipients.

BACKGROUND: A crucial step in cell cycle progression is the activation of the insulin-like growth factor I (IGF-I) receptor (IGF-IR) by its ligand. Earlier, we found estradiol 17-beta treatment of cardiac allograft recipients attenuates transplant arteriosclerosis; this was associated with inhibition of vascular cell proliferation induced by IGF-I. The current study demonstrates regulation of IGF-IR by estradiol 17-beta in vivo and in vitro in recipient native and allograft aorta and in aorta smooth muscle cells (SMCs). METHODS: Twenty cardiac transplant recipient rabbits were treated with estradiol 17-beta (100 microg/kg/day) or placebo for 6 weeks. IGF-IR expression in the coronary arteries of rabbits was demonstrated by immunohistochemistry. Reverse transcription-polymerase chain reaction and RNase protection assay were used to detect IGF-IR mRNA in rabbit aortas and cultured aortic SMCs in the presence or absence of estradiol 17-beta in vitro. IGF-I-induced cell proliferation was performed with the aorta explants and aorta SMCs from estradiol- or placebo-treated rabbits. RESULTS: Estradiol 17-beta treatment of rabbits significantly inhibited IGF-IR expression in the allograft coronary arteries and abrogated cell proliferation induced by IGF-I in the allograft aorta compared with placebo-treated recipients (65.4+/-5% vs. 500+/-139%, P<0.002). Expression of IGF-IR mRNA in the allograft aorta of placebo-treated recipients was significant higher than that of the native aorta (286+/-56%, P<0.02). Estradiol treatment significantly inhibited IGF-IR mRNA expression in the aorta versus that of the placebo-treated recipients (65+/-8.5% vs. 140+/-23%, P<0.02). Repression of IGF-IR mRNA expression in aortic SMCs by estradiol in vitro was in a concentration-dependent manner (P<0.02). CONCLUSION: Repression of IGF-IR protein and mRNA by estradiol 17-beta in vivo and in vitro suggest that one of the mechanisms of estradiol inhibition of SMC proliferation and transplant arteriosclerosis is down-regulation of IGF-IR.

Animals↗
PubMed2004

Effects of ultralow-dose transdermal estradiol on bone mineral density: a randomized clinical trial.

OBJECTIVE: Because small increments in levels of endogenous plasma estradiol are associated with higher postmenopausal bone mineral density, we investigated the safety and effectiveness in preventing bone loss of unopposed, very-low-dose transdermal estradiol for postmenopausal women. METHODS: This was a randomized, placebo-controlled, double-blind trial with 2-year follow-up at 9 United States clinical centers. The study population comprised 417 postmenopausal women, aged 60-80 years, with intact uterus and bone mineral density z scores of -2.0 or higher, who were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). All participants received calcium and vitamin D supplementation. Lumbar spine and total hip bone mineral density change was measured by dual-energy X-ray absorptiometry; endometrial hyperplasia incidence was assessed by endometrial biopsy. RESULTS: Median plasma estradiol level in the estradiol group increased from 4.8 pg/mL at baseline to 8.5 pg/mL at 1 year (P <.001 versus baseline) and to 8.6 pg/mL at 2 years (P <.001 versus baseline) and was unchanged in the placebo group. Lumbar spine bone mineral density increased 2.6% in the estradiol group and 0.6% in the placebo group (between-group difference 2.0%, P <.001). Mean total hip bone mineral density increased 0.4% in the estradiol group and decreased 0.8% in the placebo group (between-group difference 1.2%, P <.001). Osteocalcin levels and bone-specific alkaline phosphatase were lower in the estradiol group than the placebo group (P <.001 each). Endometrial hyperplasia developed in 1 woman in the estradiol group but in none of the placebo group (difference in 2-year rates 0.5%, 95% confidence interval 0-7.3%). CONCLUSION: Postmenopausal treatment with low-dose, unopposed estradiol increased bone mineral density and decreased markers of bone turnover without causing endometrial hyperplasia.

Administration, Cutaneous↗
PubMed2005

Topical application of 17beta-estradiol increases extracellular matrix protein synthesis by stimulating tgf-Beta signaling in aged human skin in vivo.

To investigate the effects of topically applied 17beta-estradiol on the expression of extracellular matrix proteins in aged human skin, 17beta-estradiol (0.01%) and its vehicle (70% propylene glycol, 30% ethanol) were applied to aged (68-82 y, eight females and five males) human buttock skin under occlusion for 2 wk (three times per week). Topical 17beta-estradiol was found to increase the expression of type 1 procollagen mRNA and protein significantly in human aged skin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta-estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited 17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We also found that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and elastic fibers in aged skin were also increased by topical 17beta-estradiol. Topical 17beta-estradiol also increased keratinocyte proliferation and the epidermal thickness in aged human skin. We also observed the same effects of topical 17beta-estradiol in young skin. In conclusion, our results suggest that topical 17beta-estradiol treatment may improve the cutaneous function of aged human skin by improving the connective tissue and increasing epidermal thickness.

Administration, Topical↗
PubMed2003

17Beta-estradiol as a receptor-mediated cardioprotective agent.

Cardiac tissue that undergoes an ischemic episode exhibits irreversible alterations that become more extensive upon reperfusion. Estrogen treatment has been reported to protect against reperfusion injury, but the mechanism remains unknown. The cardioprotective effects of 17beta-estradiol, a biologically active form of the hormone, and 17alpha-estradiol were assessed in an in vivo occlusion-reperfusion model. Anesthetized, ovariectomized rabbits were administered 17beta-estradiol (20 microg), 17alpha-estradiol (1 mg), or vehicle intravenously 30 min before a 30-min occlusion of the left anterior descending (LAD) coronary artery followed by 4 h of reperfusion. Infarct size as a percentage of area at risk decreased in the 17beta-estradiol-treated group (18.8 +/- 1.7) compared with 17alpha-estradiol (41.9 +/- 4.8; P < 0.01) or vehicle groups (48 +/- 5.5; P < 0.001). Similar results were obtained when infarct size was expressed as a percentage of total left ventricle. The second objective of the study was to assess fulvestrant (Faslodex, ICI 182,780), an estrogen receptor antagonist, for its effects on infarct size in ovariectomized female rabbits treated with 17beta-estradiol. ICI 182,780 was administered intravenously 1 h before the administration of 17beta-estradiol (20 microg) or vehicle. The hearts were subjected to 30-min LAD coronary artery occlusion and 4 h of reperfusion. Pretreatment with ICI 182,780 significantly limited the infarct size sparing effect of 17beta-estradiol when expressed as a percentage of the risk region (53.0 +/- 5.0). The results indicate that 17beta-estradiol protects the heart against ischemia-reperfusion injury and that the observed cardioprotection is mediated by the estrogen receptor.

Animals↗
PubMed1983

Enzymatic sulfation of steroids. XVIII. study of the specific estradiol-17 beta sulfotransferase of rat liver cytosol, that converts the estrogen to its 3-sulfate, and some elements of the endocrine control of its production.

A radioisotopic assay for cytoplasmic estradiol-17 beta sulfotransferase activity in rat liver was developed. Routine enzyme assays used 120 microM [3H]estradiol-17 beta, 240 microM 3'-phosphoadenosine-5'-phosphosulfate, and enzyme samples containing up to 0.60 mg of cytosol protein. Livers from males and females sulfated 934 +/- 231 and 861 +/- 266 nmol estradiol-17 beta . h-1 . g-1. DEAE-Sephadex A-50 chromatography showed that most of the cytoplasmic enzyme activity eluted as one peak that was well separated from glucocorticoid and 3 beta-hydroxysteroid sulfotransferases. Pooled column fractions containing this estradiol-17 beta sulfotransferase exhibited kinetic properties similar to the enzyme activity in cytosol, but gave slightly greater activity with 180 microM estradiol-17 beta and 360 microM 3'-phosphoadenosine-5'-phosphosulfate. Apparent Km's for the steroid and the coenzyme were 71-85 and 80-93 microM, respectively. The pH optimum for the enzyme reaction was 7.75 +/- 0.25. The enzyme sulfated estradiol-17 beta at all concentrations tested between 10 and 180 microM. It did not sulfate estrone, testosterone, dehydroepiandrosterone, or cortisol well at any test concentration between 10 and 120 microM. The sulfation product was estra-1,3,5-triene-17 beta-ol-3-sulfate. The molecular weight of the enzyme was 54 500 +/- 2300 by Sephadex G-100 chromatography. The estradiol-17 beta sulfotransferase was inhibited strongly by phenols, but not by corticosterone, deoxycorticosterone, dehydroepiandrosterone, estrone, progesterone, or testosterone. Adrenalectomy diminished the estradiol-17 beta sulfotransferase activity greatly, owing to decreases of the specific estradiol-17 beta sulfotransferase concentration. The possible relationships between the specific estradiol-17 beta sulfotransferase and other sulfotransferases in rat liver are discussed.

Adrenal Glands↗
PubMed1999

Does estradiol mediate leptin's effects on adiposity and body weight?

The role of estradiol in mediating leptin's effects on body weight was assessed in ovariectomized (OVX) mice before and after the onset of obesity. Ovariectomy did not alter leptin levels before the onset of obesity, and estradiol adminstration (0.05-17 microgram/day for 14 days) did not significantly alter leptin levels if they were corrected for the estradiol-induced reduction in body fat. The converse was also true, in that leptin administration (0.4-140 microgram/day) did not alter estradiol levels in intact mice. Furthermore, neither estradiol reduction (via ovariectomy) nor addition (via exogenous administration) significantly altered leptin's ability to reduce fat mass. Leptin was equally effective in reducing body weight in lean or obese OVX mice and intact controls. Finally, estradiol did not change the magnitude of leptin's effect on fat mass reduction when it was given in combination with leptin to lean intact or OVX mice. Estradiol may have indirectly affected leptin efficacy, because leptin did not produce as large a change in fat mass at lower doses in lean OVX mice as it did in intact counterparts. Taken together, these data suggested that 1) estradiol does not directly regulate leptin secretion or its effects on fat mass and 2) leptin does not directly regulate estradiol secretion or its effects on fat mass. Leptin and estradiol, however, may interact in an indirect fashion to affect fat utilization.

Adipose Tissue↗
PubMed1996

Effects of 17 beta-estradiol on coronary microvascular responses to endothelin-1.

The objective of this study was to examine the effects of 17 beta-estradiol on responses of coronary microvessels to endothelin-1 (ET-1). With the use of isolated pressurized coronary microvessels from the left ventricle of male or female dogs, constrictions to ET-1 were similar in vessels from male and female dogs. 17 beta-Estradiol (1 microM) attenuated constriction to ET-1 of small arteries from both male (percent constriction at 10 microM control: 39 +/- 9%, estradiol: 3 +/- 2%; P < 0.05) and female (percent constriction at 10 microM control: 39 +/- 8%, estradiol: 6 +/- 3%; P < 0.05) dogs similarly. In contrast, testosterone (1 microM) had no effect on constriction to ET-1. Constrictions to ET-1 were completely abolished by BQ-123 (1 microM), a selective ETA-receptor antagonist, and enhanced by BQ-788 (1 microM), a selective ETB-receptor antagonist. Constrictions to ET-1 alone were not altered by indomethacin (Indo, 10 microM) or NG-nitro-L-arginine (L-NNA, 100 microM). 17 beta-Estradiol produced dose-dependent relaxation of coronary microvessels preconstricted with ET-1 that was similar to the response to testosterone and progesterone. Indo or L-NNA alone had no effect on relaxation to 17 beta-estradiol. However, the combination of Indo and L-NNA attenuated Taxation to 17 beta-estradiol (percent dilation at 1 microM control: 64 +/- 13%; Indo plus L-NNA: 21 +/- 6%; P < 0.05) but did not affect relaxation to testosterone. Thus 17 beta-estradiol attenuated constrictions of coronary microvessels to ET-1 more than did similar concentrations of testosterone. The ability of 17 beta-estradiol to modulate responses to endothelin may involve release of vasodilator prostaglandins and/or nitric oxide by 17 beta-estradiol.

Animals↗
PubMed2003

The effect of estradiol in the striatum is blocked by ICI 182,780 but not tamoxifen: pharmacological and behavioral evidence.

Estradiol in the striatum enhances amphetamine (AMPH)- or KCl-stimulated dopamine (DA) release and the pacing of sexual behavior in the female rat. These effects of estradiol in the striatum are rapid, steroid specific and thought to be mediated by a G protein-coupled membrane receptor for estradiol. In the current experiments, we examined whether two antiestrogens, ICI 182,780 (ICI) and tamoxifen (TAM), affect the enhancement by estradiol of (1) AMPH-induced DA release from striatal tissue in vitro, and (2) paced mating behavior in the female rat. The steroidal antiestrogen ICI significantly blocked the effect of estradiol on AMPH-induced striatal DA release. In contrast, the nonsteroidal, triphenylethylene antiestrogen TAM did not block the effect of estradiol, even when a concentration 10 times the concentration of estradiol was delivered to the tissue. Neither of the compounds showed estrogenic action when tested in the absence of estradiol. When implanted into the dorsolateral striatum, ICI inhibited the effect of estradiol on pacing of sexual behavior, while TAM did not. The specific effects of ICI, but not TAM, on striatal DA release and pacing behavior provide further information about the binding site for estradiol in the striatum.

Amphetamine↗
PubMed1980

Comparative studies of prolactin secretion in estradiol-primed and normal male rats induced by ether stress, pimozide and TRH.

The differences in plasma prolactin concentration between normal and estradiol-implanted male rats were compared after treatment with 3 different stimulating agents of prolactin secretion [ether anesthesia, pimozide (a "specific' dopaminergic receptor blocking agent) and TRH] using conscious, free-moving rats implanted with permanent intra-atrial cannulae. It has recently been shown that ether stress raises the circulating prolactin concentration by stimulating PRF secretion. The ether stress elevated prolactin concentration from 100 to 400 ng/ml in the estradiol-implanted rat and from 10 to 40 ng/ml in the normal male. Thus, the ether stress elevated the prolactin concentration 4 times over the basal level in both normal male and estradiol-implanted male rats, implying that the physiological role of the PRF is not changed by the estradiol implantation. A bolus injection of pimozide (1 mg/kg) elevated the plasma prolactin concentration in both the normal and estradiol-implanted male with an initial surge followed by descent to a maintained plateau level. This plateau level in the estradiol-primed rat was 600 ng/ml and in the nonprimed male rat, 50 ng/ml. The ratio of the plateau concentration over the basal level was 4 times for both groups, suggesting that the physiological role of the PIF in the estradiol-implanted rat is not different from that in the normal male rat. It is known that TRH not only stimulates TSH secretion but will stimulate prolactin secretion as well. A very large dose (0.6 mg/kg) of TRH elevated prolactin concentration 6-fold in the estradiol-implanted rat but stimulate little prolactin secretion in the normal male rat. Since ether exposure appears to stimulate prolactin secretion in both estradiol-primed and non-primed male rats through PRF secretion, while TRH was not able to stimulate a significant amount of prolactin secretion in the normal male rat, we concluded that TRH acts to stimulate prolactin secretion in estradiol-primed rats but through a different mechanism than that operating for PRF.

Animals↗
PubMed1988

Importance of pituitary and neural actions of estradiol in induction of the luteinizing hormone surge in the ewe.

Two experiments were performed to test the importance of both pituitary and neural sites of action of estradiol in inducing the surge of luteinizing hormone (LH) in the ewe. Both experiments were conducted using an animal model in which pulsatile secretion of gonadotropin-releasing hormone (GnRH) and endogenous secretion of ovarian steroids were eliminated by ovariectomy during seasonal anestrus and treatment with Silastic implants which maintained a luteal-phase level of serum progesterone. The hormonal requirements for the surge were then evaluated by systematic application of GnRH and estradiol signals using pulsatile infusion pumps (for GnRH) and Silastic implants (for estradiol). In experiment 1, the circulating level of estradiol and frequency of GnRH pulses were increased either abruptly or progressively (i.e. mimicking the changes in the estrous cycle between luteolysis and just before the LH surge). Abrupt increments led to an LH surge in all ewes; progressive rises to the same absolute levels did not. However, sudden application of a further large increase in GnRH upon the progressive rise elicited an LH surge in every instance. In experiment 2, a GnRH pulse pattern known to be effective in inducing the LH surge was applied under conditions of differing estradiol concentration: no estradiol, basal estradiol, basal rising to peak estradiol. The GnRH signal elicited high-amplitude surges of LH only in the presence of a peak estradiol concentration. Our findings are consistent with the conclusion that two actions are required for a rise in estradiol to elicit a full-amplitude surge of LH in the ewe: an action on the brain to evoke a sudden increase in GnRH release and an action on the pituitary to maximize its response to GnRH.

Animals↗