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PubMed1984

Effect of estradiol and relaxin on growth of fibroblastic cells isolated from guinea pig mammary glands.

Fibroblasts were isolated from the mammary glands of guinea pigs and grown in 96-well culture plates. They were treated with a factorial arrangement of porcine relaxin (0.0, 0.5, 1.0 or 1.5 micrograms/ml) and estradiol-17 beta (0, 200, 400 or 600 pg/ml). Tritiated thymidine or uridine was added to a final activity of 25 nCi per well and the cells incubated at 37 degrees C for 48 h. Cells were then harvested onto filter paper and counted for tritium. Controls (0.0 micrograms/ml relaxin and 0 pg/ml estradiol) incorporated 3.7 nCi of tritiated thymidine and 4.8 nCi tritiated uridine. Both relaxin and estradiol altered the incorporation of thymidine and uridine. There was also an interaction between the two hormones. Thymidine incorporation with no estradiol and 1.5 micrograms/ml relaxin was 129% of controls. The optimum incorporation of thymidine occurred with 0.5 micrograms/ml relaxin and 400 pg/ml estradiol. This combination of hormones gave a response of 145% of controls. Uridine incorporation followed a different pattern. Relaxin alone at a concentration of 1.5 micrograms/ml gave a near-optimum response of 141% of control. The optimum combination of relaxin and estradiol for uridine incorporation was 1.5 micrograms/ml relaxin and 400 pg/ml estradiol, which gave a response of 156% of controls. These data indicated that relaxin and estradiol alter DNA and RNA synthesis in mammary fibroblasts and thus may be important in controlling the growth of the mammary gland stroma.

Animals↗
PubMed1995

Estradiol and progesterone influence the synthesis of gonadotropins in the absence of gonadotropin-releasing hormone in the ewe.

Acute actions of estradiol and progesterone on synthesis and secretion of gonadotropins without the confounding effects of endogenous steroids and GnRH were examined by using the ovariectomized (OVX), hypothalamic-pituitary-disconnected (HPD) ewe. Thirty-two OVX ewes were subjected to HPD and randomly assigned to eight groups (4 ewes/group). An additional four OVX ewes served as controls. Each of 12 OVX-HPD ewes received 4 s.c. implants of estradiol 24 h after HPD (implantation was designated as Time 0 h). Sixteen OVX-HPD ewes received no treatment and served as contemporary controls. The remaining four OVX-HPD ewes received implants of estradiol for 48 h and were administered 16 mg progesterone i.m. twice daily in the last 24 h of estradiol treatment. Blood samples and pituitary glands were collected from OVX-HPD control and steroid-treated ewes at 0, 12, 24, and 48 h. Amounts of gonadotropin subunit mRNAs and serum concentrations of gonadotropins were decreased at 24 h after HPD and remained unchanged thereafter in OVX-HPD controls. Although treatment with estradiol decreased pituitary content of LH and steady-state levels of mRNA for LH beta-subunit (p < 0.05) compared to contemporary controls, serum concentrations of LH were not affected. Serum concentrations and pituitary content of FSH decreased (p < 0.05) 24 h after initiating treatment with estradiol, but steady-state levels of FSH beta-subunit mRNA were unchanged. There was a transient decrease in pituitary content of FSH at 24 h of estradiol treatment. Steady-state levels of mRNA for alpha-subunit were unaffected by estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Immunoneutralization of inhibin and estradiol during the follicular phase of the estrous cycle in cows.

To investigate the physiological importance of inhibin and estradiol in the regulation of FSH secretion during the follicular phase of the estrous-cycle in cows, animals were passively immunized against the two hormones. Sixteen cows were divided into four equal groups and given injections of prostaglandin F2 alpha (PG) i.m. twice at 8-h intervals on Day 10 of the estrous cycle (Day 0 = day of estrus) to induce luteal regression. At 48 h after the first PG injection, each group of four cows received injections of one of the following: 100 ml castrated goat serum (control serum), 100 ml antiserum against inhibin, 100 ml antiserum against estradiol, or a combination of 100 ml inhibin antiserum and 100 ml estradiol antiserum. The LH surge occurred within 2 days after injection of the control serum or inhibin antiserum, whereas it was not detected in either of the groups passively immunized against estradiol, indicating that passive immunization against estradiol blocks a positive feedback effect of estradiol on LH secretion. There was no clear difference in basal concentrations of LH among the four groups. Injection of the inhibin antiserum resulted in a marked increase (p < 0.01) in plasma concentrations of FSH compared with values in the control group, while there were no significant changes in concentrations of plasma FSH after injection of the estradiol antiserum. Combined administration of the inhibin and estradiol antisera also produced a marked increase (p < 0.01) in plasma concentrations of FSH. The FSH response to the combined immunization was longer in duration than the FSH response to immunization with inhibin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Differential regulation of progesterone and estradiol production by mouse cumulus and mural granulosa cells by A factor(s) secreted by the oocyte.

Mouse oocytes secrete a factor(s) that inhibits progesterone and enhances estradiol production by cumulus granulosa cells. The purpose of this study was to investigate the mechanisms by which the production of these steroids is modulated. Mouse oocyte-cumulus cell complexes (intact) and complexes from which the oocytes were removed microsurgically (oocytectomized; OOX) were cultured for up to 48 h in the presence of FSH (150 ng/ml) and testosterone (5 x 10(-7) M). For these experiments, all cells were obtained from antral follicles of 24- to 26-day-old mice primed with eCG. Intact complexes produced primarily estradiol, with significant accumulation occurring between 24 and 48 h. In contrast, OOX complexes produced little estradiol but, starting at 18 h of culture, released significantly more progesterone than did intact complexes. Progesterone accumulation in cocultures of denuded oocytes with either OOX complexes or monolayers of mural granulosa cells was significantly reduced compared to that with OOX complexes or mural granulosa cells cultured alone. If dibutyryl cAMP replaced FSH in the cocultures, similar results were obtained, suggesting that the oocyte-secreted steroid-regulating factor acts downstream of the generation of cAMP to inhibit progesterone production. Since estradiol can inhibit progesterone production by granulosa cells, we investigated the possibility that the increased progesterone released by OOX complexes was secondary to the lower estradiol production. Intact complexes cultured in the presence of the nonaromatizable androgen, 5 alpha-dihydrotestosterone, or steroidal (4-hydroxyandrostenedione) or non-steroidal (CGS 16949A) aromatase inhibitors produced little estradiol; however, progesterone production by these complexes was no different from that of estradiol-producing intact complexes. These results suggest that the steroid-regulating factor(s) secreted by occytes acts to regulate granulosa cell production of estradiol and progesterone by independent mechanisms.

Animals↗
PubMed1997

Contributions of endogenous inhibin and estradiol to the regulation of follicle-stimulating hormone and luteinizing hormone secretion in the pregnant rat.

To examine the contributions of endogenous inhibin and estradiol to the regulation of FSH and LH secretion in the pregnant rat, some rats were passively immunized against inhibin and/or estradiol, and others were ovariectomized, on Days 5, 10, 15, and 20 of pregnancy. Ovarian and uterine venous blood was collected separately to confirm the sources of inhibin and steroid hormones during pregnancy. Immunoreactivity of inhibin in the placenta was also examined by RIA. Levels of inhibin in ovarian venous plasma were significantly higher than those in peripheral plasma during pregnancy. No difference was observed between the levels of inhibin in uterine venous plasma and peripheral plasma. No immunoreactivity of inhibin was detected in placental homogenate from rats at Days 10, 15, and 20. FSH secretion significantly increased after immunoneutralization of inhibin during pregnancy. A marked increase in FSH secretion was noted on Days 5 and 20, and the smallest increase was observed on Day 15. Administration of estradiol antiserum (AS) alone did not induce a significant increase in FSH secretion on any day of pregnancy. However, a synergistic effect of estradiol AS and inhibin AS was observed on Day 20. On Days 5, 10, and 20, administration of inhibin AS or estradiol AS induced a significant increase in LH secretion. A synergistic effect of inhibin AS and estradiol AS on LH secretion was observed on Day 5. On Days 5 and 10, significantly high LH secretion was noted in ovariectomized rats as compared with that in rats treated with both inhibin AS and estradiol AS, indicating that other ovarian hormones such as progesterone may be involved in the suppression of LH secretion in these stages of pregnancy. These data indicate that both inhibin and estradiol, predominantly secreted from the ovary, are involved in the regulation of gonadotropin secretion during pregnancy as during the estrous cycle in the rat.

Animals↗
PubMed2005

17 beta-estradiol transiently disrupts adherens junctions in endothelial cells.

Interendothelial junctions are important regulators of endothelial cell functions such as migration and proliferation, major features in angiogenesis, and endothelial cell monolayer wound healing. 17beta-estradiol regulates these functions in vivo and in vitro and also increases endothelial monolayer permeability as it results from impaired monolayer integrity and intercellular adhesion. We hypothesized that 17beta-estradiol affects these cell adhesion-dependent functions in endothelial cells by targeting the adherens junction complex. Here, we show that 17beta-estradiol increases uterine microvascular endothelial cell monolayer permeability and transiently redistributes interendothelial junction-forming proteins in endothelial cells. Concomitantly, adherens junction proteins are disconnected from the cytoskeleton and alpha-catenin, which links VE-cadherin to the cytoskeleton, is redistributed from the membrane and the adherens junction complex. Furthermore, 17beta-estradiol increased tyrosine phosphorylation of the adherens junction complex. These effects were inhibited by the estrogen receptor antagonist ICI 182,780 but could be provoked using non-cell membrane-permeable 17beta-estradiol-BSA in all cells tested, including EA.hy 926 cells, which have been shown unable to stimulate 17beta-estradiol-dependent gene transcription. Additionally, 17beta-estradiol treatment enhanced the angiogenic effect of vascular endothelial growth factor in an in vitro angiogenesis model, as a potential implication of the adherens junction disruption. Cotreatment with the Src-family kinase inhibitor PP2 prevented the redistribution and phosphorylation of the adherens junction proteins. Taken together, our data show that adherens junctions in endothelial cells are a downstream target of membrane-associated 17beta-estradiol signaling, possibly through Src-family kinases.

Adherens Junctions↗
PubMed2001

Relaxant effects of 17-beta-estradiol in cerebral arteries through Ca(2+) entry inhibition.

Estrogens account for gender differences in the incidence and outcome of stroke, but it remains unclear to what extent neuroprotective effects of estrogens are because of parenchymal or vascular actions. Because reproductive steroids have vasoactive properties, the authors assessed the effects and mechanisms of action of 17-beta-estradiol in rabbit isolated basilar artery. Cumulative doses of 17-beta-estradiol (0.3 micromol/L to 0.1 mmol/L) induced concentration-dependent relaxation that was larger in basilar than carotid artery, in male than female basilar artery, and in KCl-precontracted than UTP-precontracted male basilar artery. Endothelium removal did not modify relaxation induced by 17-beta-estradiol in basilar artery, whereas relaxation induced by acetylcholine (1 nmol/L to 0.1 mmol/L) was almost abolished. Neither the estrogen receptor antagonist ICI 182,780 (1 micromol/L), nor the protein synthesis inhibitor cycloheximide (1 micromol/L) affected 17-beta-estradiol-induced relaxations. Relaxations induced by the K(+) channel openers NS1619 and pinacidil in the same concentration range were greater and lower, respectively, when compared with relaxation to 17-beta-estradiol, which was not significantly modified by incubation with the K(+) channel blockers charybdotoxin (1 nmol/L and 0.1 micromol/L) or glibenclamide (10 nmol/L and 1 micromol/L). Preincubation with 17-beta-estradiol (3 to 100 micromol/L) produced concentration-dependent inhibition of CaCl(2)-induced contraction, with less potency than the Ca(2+) entry blocker nicardipine (0.01 to 10 nmol/L). The authors conclude that 17-beta-estradiol induces endothelium-independent relaxation of cerebral arteries with tissue and gender selectivity. The relaxant effect is because of inhibition of extracellular Ca(2+) influx to vascular smooth muscle, but activation of estrogen receptors, protein synthesis, or K(+) efflux are not involved. Relatively high pharmacologic concentrations of 17-beta-estradiol causing relaxation preclude acute vascular effects of physiologic circulating levels on the cerebral circulation.

Animals↗
PubMed1996

Estradiol effect on rate of proliferation of rat carotid segments: effect of gender and tamoxifen.

Using organ culture of carotid artery segments from sexually mature male and female rats, we examined the effect of estradiol 17 beta on proliferation. The index of cell proliferation was [3H]thymidine uptake. Estradiol 17 beta (0.18-0.36 microM) inhibited the uptake of thymidine in a concentration-dependent manner (p < 0.05). Estradiol 17 beta inhibited [3H]thymidine uptake only in the absence of the weak estrogen receptor agonist phenol red and in carotid artery segments from sexually mature female (p < 0.01) but not male rats. Tamoxifen (0.1 and 1 microM), a partial agonist of estrogen receptors, significantly inhibited thymidine uptake (p < 0.01). However, preincubation of the segments with tamoxifen (0.1 and 1.0 microM) for 4 h before the exposure to estradiol, blocked estradiol 17 beta-induced inhibition of thymidine uptake (p < 0.05 and p < 0.01 for 0.1 and 1.0 microM, respectively). The cyclooxygenase inhibitor indomethacin (5 microM) did not affect either the basal [3H]thymidine uptake or the estradiol 17 beta-induced inhibition of that uptake. This latter finding suggests that prostacyclin or prostaglandin E2 does not mediate the inhibitory response to estradiol 17 beta. The results of these experiments suggest that estradiol 17 beta-induced inhibition of proliferation of rat carotid artery segments is mediated through activation of estrogen receptors.

Animals↗
PubMed2006

Habitual physical activity and estradiol levels in women of reproductive age.

Variation in the risk of breast cancer observed among women and among populations may be explained by variation in lifetime exposure to estrogens. The suppressive effect of exercise on estradiol levels in women is well documented, but it is unknown whether habitual (i.e. typical daily) physical activity has a similar effect. Epidemiological data suggest that physical activity is one of the few modifiable factors capable of reducing the risk of breast cancer in women. We investigated whether variation in the amount of habitual activity corresponds to variation in estradiol levels in women of reproductive age. One hundred and thirty-nine regularly menstruating women 24-37 years of age collected daily saliva samples for one complete menstrual cycle and kept a daily log of physical activity. Saliva samples were analyzed for concentration of estradiol. We observed a negative relationship between habitual physical activity and salivary levels of estradiol. Mean estradiol was 21.1 pmol/l in the low, 17.9 pmol/l in the moderate and 16.6 pmol/l in the high activity group (all pairwise differences were statistically significant at P<0.009). A strong association exists between physical activity and levels of estradiol among women of reproductive age. A modern lifestyle, characterized by reduced physical activity, may therefore contribute to a rise in the levels of estradiol produced during menstrual cycles and thus to higher cumulative lifetime exposure to estradiol, resulting in a higher risk of breast cancer.

Adipose Tissue↗
PubMedDate not supplied

Soy phytoestrogens improve radial arm maze performance in ovariectomized retired breeder rats and do not attenuate benefits of 17beta-estradiol treatment.

OBJECTIVE: Soy phytoestrogens (SPEs) seem to have beneficial effects on the cardiovascular system with no adverse effects on the breast and uterus. Our objective was to examine the effects of oral estradiol alone, soy protein with phytoestrogens alone, and combinations of estradiol and SPEs on working memory of ovariectomized retired breeder female rats using the radial arm maze test. DESIGN: Eighty-four bilaterally ovariectomized retired breeder female rats were randomized into 12 groups to examine the effects of chronic treatment (10 months) with oral micronized estradiol (0, 0.5, 1, and 2 mg/1,800 Cal), SPEs (0, 72, and 144 mg/1,800 Cal), and all combinations of these doses of estradiol and SPEs on working memory. RESULTS: Oral administration of estradiol or SPEs resulted in a dose-dependent improvement in the performance of the radial arm maze tests. In addition, at each of the three doses of oral micronized estradiol tested, the performance of the radial arm tests was not significantly different in the presence or absence of SPEs. CONCLUSIONS: Our data suggest that SPEs may function as estrogen agonists in improving working memory in the ovariectomized retired breeder female rats and that SPEs do not antagonize the beneficial effects of estradiol on the working memory of these rats. No additional benefits on the radial arm maze test performance were observed with the tested combinations of estradiol and SPEs.

Animals↗
PubMed2003

Effect of estradiol administration on splanchnic perfusion after trauma-hemorrhage and sepsis.

PURPOSE OF REVIEW: This review focuses on the latest mechanistic understanding of the effects of estradiol on the splanchnic circulation and the possibility of estradiol treatment as an adjunct for the treatment of trauma-hemorrhage and sepsis. RECENT FINDINGS: Systemic hypotension induced by shock accompanies marked alterations in blood flow to various organs. Decreased splanchnic perfusion is frequently observed after insults, such as severe hemorrhage or sepsis, which leads to the destruction of the intestinal mucosal barrier and hepatic dysfunction. Studies suggest that estradiol acts as a facilitator of the intestinal blood flow via the increased production of nitric oxide, decreased production of vasoconstrictors, attenuated neutrophil adhesion, and decreased formation of oxygen free radicals. SUMMARY: Trauma-hemorrhage results in decreased circulating blood volume. In contrast, sepsis is an inflammatory state mainly mediated by bacterial products. However, these divergent insults show similar pathophysiologic alterations in terms of the splanchnic circulation. Because estradiol effectively protects the organs from circulatory failure after various adverse circulatory conditions, many studies are being performed to clarify the molecular mechanism of estradiol action with regard to tissue circulation. Estradiol improves the macro- and microcirculation of the splanchnic organs by multiple mechanisms. Nonetheless, it remains unclear which mechanism plays the most important role in the treatment of trauma-hemorrhage and sepsis. Additional studies are required to elucidate the precise mechanism of estradiol action and to determine the usefulness of estradiol treatment for severe hemorrhage and sepsis in patients.

Animals↗
PubMed2003

Ethanol and estradiol modulate alternative splicing of dopamine D2 receptor messenger RNA and abolish the inhibitory action of bromocriptine on prolactin release from the pituitary gland.

BACKGROUND: Several reports show evidence for the existence of high levels of prolactin (PRL) in alcoholic men and women. Previously we have shown that ethanol increases PRL release both in vivo and in vitro. How ethanol increases PRL release is not well understood. METHODS: In this study, we determined the effects of ethanol in the presence and absence of estradiol-17 beta on PRL messenger RNA (mRNA) levels, dopamine D2 receptor mRNA splicing, and the PRL-inhibitory response of a dopaminergic agent, bromocriptine, in the pituitary of Fischer-344 rats and in primary cultures of anterior pituitary cells. Real-time reverse transcriptase-polymerase chain reaction was used for mRNA detection, and radioimmunoassay was used for hormone detection. RESULTS: Estradiol and ethanol alone increased PRL mRNA expression in the pituitary gland. Ethanol also potentiated estradiol action on PRL mRNA expression in the pituitary. Determination of the D2 receptor splicing, by determining the changes in the percentage of D2 receptor mRNA expressed as its long form (D2L) and as its short form (D2S), revealed that both ethanol and estradiol altered D2 receptor splicing. Ethanol and estradiol, alone and together, increased the percentage of the D2L receptor but decreased the D2S receptor percentage. Similarly, ethanol and estradiol alone and in combination increased D2L, but decreased the D2S receptor percentage in primary cultures of pituitary cells. Evaluation of bromocriptine's inhibition of PRL release in primary cultures of pituitary cells indicated that ethanol reduced the ability of this D2 receptor agonist to inhibit PRL release. CONCLUSIONS: These results confirm estradiol's inhibition of D2 function and provide novel evidence that ethanol, like estradiol, reduces dopamine's ability to inhibit PRL release by modifying alternative splicing of the dopamine D2 receptor in the pituitary.

Alternative Splicing↗
PubMedDate not supplied

Effects of ultralow-dose transdermal estradiol on postmenopausal symptoms in women aged 60 to 80 years.

OBJECTIVE: To investigate the effect of ultralow-dose transdermal estradiol on postmenopausal symptoms and side effects in a cohort of largely asymptomatic postmenopausal women aged 60 to 80 years. DESIGN: This secondary analysis used data from the UltraLow-dose Transdermal estRogen Assessment trial, a randomized, placebo-controlled, double-blind trial in postmenopausal women to determine the skeletal effects and safety of ultralow-dose transdermal estradiol. Four hundred seventeen postmenopausal women, aged 60 to 80 years, were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). Participants were queried at each clinic visit about postmenopausal symptoms and side effects purported to be associated with estrogen therapy using a standardized questionnaire. RESULTS: At baseline, 16% of women reported hot flashes, 32% reported vaginal dryness, and 35% reported trouble sleeping. Women who received ultralow-dose estradiol were no more likely to report improvement of hot flashes, vaginal dryness, or sleep difficulties than those who received placebo. Treatment with ultralow-dose estradiol did not cause breast tenderness, uterine bleeding, or other symptoms often attributed to estrogen, but vaginal discharge was more common in women who received estradiol compared with those who received placebo. CONCLUSION: In this population of older, largely asymptomatic women, ultralow-dose transdermal estradiol did not improve postmenopausal symptoms and did not cause side effects other than vaginal discharge. Further study is needed to determine whether this dose of transdermal estradiol is effective in treating symptoms of postmenopause in younger, more symptomatic women.

Administration, Cutaneous↗
PubMed1975

The effect of estradiol on the cell kinetics in the uterine and cervical epithelium of neonatal mice.

The effect of estradiol-17beta on the length of the various phases of the cell cycle was studied in the neonatal mouse uterine, and cervical epithelium. A double labelling method was used, and in addition labelled mitoses were counted. In the uterus proper, estradiol shortens the length of the total cell cycle. TC, from 17-9 hr to 15-7 hr, and the duration of S phase, Ts from 6-7 to 5-1 hr 6 hr after estradiol treatment. 12 hr after estradiol treatment, TC is shortened to 7-4 hr and Ts to 4-5 hr. The shortening of TC at 12 hr is manily due to an effect on TG1, which is shortened from 8-55 hr in untreated animals to 1-8 hr in estradiol treated animals. The TC of cervix epithelium cells in untreated animals was found to be 21-8 hr. After treating the mice for 6 hr with estradiol the tc was now increased to 47 hr and further to 61-2 hr following 12 hr treatment with the hormone. Ts increases from 8-3 hr to 15-2 hr following 6 hr estradiol treatment, and to 15-4 hr after 12 hr treatment. The effect is most pronounced in TG1, which is lengthened from 10-95 hr in untreated animals to 28-1 hr and 43 hr, respectively, in animals treated for either 6 or 12 hr with estradiol.

Animals↗
PubMed2004

Estradiol reverses renal injury in Alb/TGF-beta1 transgenic mice.

BACKGROUND: Men with chronic renal disease progress more rapidly to renal failure than do women. Tranforming growth factor-beta (TGF-beta) plays a central role in promoting progressive renal injury, in part due to transcriptional effects mediated by cooperation between Smad proteins and the transcription factor Sp1. Estrogen negatively regulates Sp1 activity and reverses the stimulatory effects of TGF-beta on type IV collagen synthesis and cellular apoptosis in cultured mesangial cells. We hypothesized that the ability of estradiol to reverse the effects of TGF-beta underlies gender dimorphism in the progression of chronic renal disease. METHODS: We studied Alb/TGF-beta transgenic mice, which overexpress TGF-beta1 and develop proteinuria and progressive glomerulosclerosis. We implanted a sustained-release estradiol pellet or a placebo pellet into control and Alb/TGF-beta transgenic mice at 2 weeks of age. Animals were sacrificed at 5 weeks, at which time urine, blood, and renal tissue were obtained for study. RESULTS: The sustained-release estradiol pellet achieved a physiologic concentration of estradiol. TGF-beta levels were higher in estradiol-treated mice compared to placebo-treated mice. Proteinuria was reduced in estradiol-treated Alb/TGF-beta mice compared to placebo-treated transgenic mice. Mesangial expansion and closure of capillary loops with enhanced glomerular deposition of type I collagen, type IV collagen, and tissue inhibitor of metalloproteinase (TIMP-2) was observed in glomeruli of placebo-treated transgenic mice. Estrogen therapy reversed these abnormalities. CONCLUSION: Administration of estradiol to Alb/TGF-beta transgenic mice, which overexpress TGF-beta, ameliorated progressive renal injury. The ability of estradiol to reverse the pro-fibrotic effects of TGF-beta, both in vitro and in vivo, may underlie the sexual dimorphism in renal disease progression observed in humans.

Animals↗
PubMed1981

Somatostatin inhibits prolactin secretion in the estradiol primed male rat.

Somatostatin inhibits not only growth hormone secretion, but also the secretion of several other hormones. The role of somatostatin in prolactin (PRL) secretion has not been clearly demonstrated. The present study was undertaken to examine the effects of somatostatin on rat PRL secretion in several different circumstances where the circulating PRL level is elevated: (1) the estradiol primed intact male rat, (2) normal and (3) estradiol primed rats pretreated with pimozide, (4) normal and (5) estradiol primed hypophysectomized male rats with adenohypophyses grafted under the kidney capsule (HAG rat). Blood samples (70 microL) were taken every 2 min via an indwelling atrial cannula from conscious, unrestrained animals. In the estradiol primed intact rats, a bolus injection of somatostatin (10, 100, and 1000 micrograms/kg) lowered PRL levels in a dose-dependent manner. When the PRL concentration was elevated by the administration of pimozide (3 mg/kg), a dopaminergic receptor blocking agent, somatostatin was ineffective in decreasing plasma PRL concentration but the PRL concentration was lowered by somatostatin when the rat had been primed with estradiol. Somatostatin had no effect on the normal HAG rats, but lowered the plasma PRL concentration in the estradiol primed HAG rats. Since somatostatin inhibits PRL secretion only in the estradiol primed rats, it is suggested that estradiol priming creates a new environment, presumably via new or altered receptors, which can be inhibited by somatostatin.

Animals↗
PubMed2002

Estradiol reduces F2alpha-isoprostane production in cultured human endothelial cells.

Free radical-generated F(2alpha)-isoprostanes are a group of compounds with vasoconstrictor properties. To investigate whether estradiol exerts antioxidant actions modifying F(2alpha)-isoprostane production, cultured human umbilical vein endothelial cells were exposed to estradiol and other compounds and F(2alpha)-isoprostanes were measured in culture medium. Exposure to 1 and 10 nM estradiol for 24 h reduced F(2alpha)-isoprostane production by 36 and 49%, respectively (P < 0.001 vs. control). Exposure to antiestrogens alone (ICI-182780 or EM-652) slightly reduced F(2alpha)-isoprostanes (P < 0.05 vs. control), but much less than exposure to estradiol (P < 0.05). ICI-182780 reversed the estradiol-induced reduction of F(2alpha)-isoprostane concentration (P < 0.05). Along with time-course analysis, these results suggest that estradiol effects were mediated through estrogen receptor-dependent and -independent mechanisms. Progestogens alone (progesterone or medroxyprogesterone acetate) did not modify F(2alpha)-isoprostane production at any of the tested concentrations (1, 10, and 100 nM). Progesterone completely reversed estradiol-induced reduction of F(2alpha)-isoprostane production (P < 0.05 vs. control and estradiol), but medroxyprogesterone acetate did not (P < 0.05 vs. control).

Cells, Cultured↗
PubMed1992

Acute effect of 17 beta-estradiol on rabbit coronary artery contractile responses to endothelin-1.

We assessed the acute effect of 17 beta-estradiol on coronary artery constrictor responses to endothelin-1. 17 beta-Estradiol significantly shifted endothelin-1, calcium, or BAY K 8644 concentration-dependent contraction curves to the right in endothelium-denuded coronary arteries isolated from nonpregnant female rabbits. The -log 50% effective dose (ED50) of calcium in high KCl medium (100 mM) was 3.8 +/- 0.11 in control and 3.2 +/- 0.1 and 2.8 +/- 0.12 after incubation with 17 beta-estradiol (1 and 10 microM, respectively). The -log ED50 of BAY K 8644 (KCl 15 mM) was 7.8 +/- 0.1 in control and 7.4 +/- 0.08 and 7.2 +/- 0.05 in the presence of 17 beta-estradiol (1 and 10 microM, respectively). The -log ED50 of endothelin-1 was 9.2 +/- 0.08 in control and 8.8 +/- 0.1, 8.4 +/- 0.07, and 8.1 +/- 0.12 after incubation with 17 beta-estradiol (3, 10, and 30 microM, respectively). Similar results were obtained from coronary arteries of male rabbits. These increases of -log ED50 values were significant (P less than 0.05 or 0.01). 17 beta-Estradiol and verapamil induced dose-dependent relaxation in both endothelium-intact or -denuded coronary arteries submaximally precontracted by endothelin-1. NG-monomethyl-L-arginine had no effect on relaxation induced by 17 beta-estradiol, whereas it eliminated relaxation induced by acetylcholine in rings with an intact endothelium. These data suggest that 17 beta-estradiol attenuates the rabbit coronary artery contraction induced by endothelin-1 via an endothelium-independent mechanism, possibly by affecting calcium influx.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗