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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen and androgen receptors were measured in the cytosol prepared from established cell lines of Sertoli, Leydig, myoid, and endothelial cells as well as in primary Sertoli cell-enriched cultures. Estradiol-binding sites with characteristics of estrogen receptors were identified in established lines of Sertoli cells from rat [43 +/- 7 (mean +/- SEM) fmol/mg protein; Kd = 1.1 nM] and mouse (34 +/- 4 fmol/mg protein; Kd = 0.9 nM). The binding sites were estrogen specific, since only estradiol and diethylstilbestrol, but not testosterone, progesterone, or dexamethasone, competed with [3H]estradiol for binding sites in the cytosol prepared from the cell lines. Exposure of the cells to estradiol (10 nM) resulted in accumulation of estrogen receptors in nuclei, with maximal uptake by 30 min. The estrogen receptor concentration was very low or undetectable (less than 10 fmol/mg protein) in primary cultures of rat Sertoli cells that were cultured for 3 days. However, after 15 days in culture, the estrogen receptor concentration increased and reached levels similar to those in the established Sertoli cell lines. No estrogen receptors were measurable in myoid or endothelial cells. By contrast, androgen receptors were identified in all five cell lines and in primary Sertoli cells cultured for 3 and 15 days. The content of both estrogen and androgen receptors in the mouse Sertoli cell line increased as a function of cell density. We conclude from these studies that androgen receptors are present in all of the testicular somatic cell lines examined and in primary Sertoli cells; estrogen receptors are present in Sertoli cell and Leydig cell lines, but not in myoid and endothelial cell lines; the low estrogen receptor concentration in Sertoli cells cultured for 3 days increases 4-fold after 15 days in culture; and cell density is a major regulator of the concentrations of estrogen and androgen receptors in the Sertoli cell line.
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PMID:Estrogen and androgen receptors in Sertoli, Leydig, myoid, and epithelial cells: effects of time in culture and cell density. 673 11

RIA for the measurement of oxytocin in human plasma is described. Extraction of oxytocin from larger peptides in plasma used acetone precipitation with a 75% +or- 2 SEM recovery of oxytocin. Nonspecific binding of the assay was less than 4% and the minimum level of detection was 0.2 mcU/tube. No cross-reactivity was noted with neurophysins, arginine, or lysine vasopressin. The mean basal level (+or- SEM) of oxytocin in men was 1.80 +or- 0.07 mcU/ml and was not different in normal women (1.71 +or- 0.07 mcU/ml). Changes in posture had no effect on the levels of oxytocin. Samples obtained every 15 minutes over 4 hours showed no pulsatile secretion of oxytocin. In women chronically receiving estrogen as an oral contraceptive, oxytocin was greater than normal (4.59 +or- 0.51 mcU/ml; P0.01). Estrogen-stimulated neurophysin was also elevated *8.45 +or- 1.99 ng/ml; P0.005). Acute ingestion of estrogen caused an increase in the level of oxytocin in plasma by 12 hours and a concomitant elevation of estrogen-stimulated neurophysin. When the neurophysin was isolated from plasma obtained from a subject after ingestion of estrogen, the neurophysin from plasma comigrated on a polyacrylamide gel with a human pituitary standard of estrogen-stimulated neurophsin. In the studies in which neurophysin was elevated, the correlation between the level of oxytocin and the level of estrogen-stimulated neurophysin in plasma was significant (P0.01). The observation that estrogen administration stimulates the release of oxytocin and estrogen-stimulated neurophysin provides additional evidence that this neurophysin is the oxytocin-neurophysin of man.
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PMID:Oxytocin in human plasma: correlation with neurophysin and stimulation with estrogen. 722 98

Estrogen-binding proteins were observed in the cytosol of human pituitary adenomas. The Kd for estradiol was 0.44 nM at 0 C, and hormonal specificity was that expected for estrogen receptors. Sucrose gradient sedimentation experiments revealed that receptors from different tumors existed in either the 8S or the 4S form or both. Of the 23 tumors examined, 14 contained estrogen receptors. Receptors were more often present and their concentration was higher in PRL-secreting adenomas (mean +/- SEM, 20.6 +/- 13.4 fmol/mg proteins; 7 determinations) than in GH-secreting adenomas (1.4 +/- 0.8 fmol/mg protein; 9 determinations) and chromophobe tumors (4.1 +/- 1.6 fmol/mg protein; 7 determinations). There was also a correlation between the presence of estrogen receptors and histological signs of cell proliferation and tumor growth.
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PMID:Estrogen receptors in human pituitary adenomas. 741 71

Estrogen treatment prevents early postmenopausal bone loss. The aim of this study was to evaluate the effects of estrogen-progestogen therapy on bone mass in elderly osteopenic postmenopausal women. Fifteen women with a mean age of 58 +/- 6 (mean +/- SD) years and 12 +/- 7 (5-31) years from menopause were evaluated. Bone mineral density (BMD) was assessed by dual X-ray absoptiometry (DXA) with 1.7% variation coefficient at lumbar spine (L2-4) and 1.9% at femur neck. Measurements were done at both sites before and after a 12 month treatment. At the beginning of the study lumbar spine BMD (LS BMD) was low: < 0.9 grs/cm2; z-score: -1.4 +/- 0.17 (mean +/- SEM). Treatment consisted in transdermal 17 beta estradiol (50 micrograms/day) (n = 10) or an equivalent natural estrogen oral dose (n = 5). Variable doses of medroxiprogesterone acetate were added on an individualized basis to women with an intact uterus (n = 12). Calcium intake was increased up to a median of 1200 mg/day (800-1600). After a one year treatment LS BMD was increased by 8.4 +/- 1.1% (mean +/- SEM) (95% CI: 6-10.8), from 0.748 +/- 0.02 to 0.810 +/- 0.02 gr/cm2 (p < 0.0001). A less marked gain in femur neck bone mineral density (FN BMD) was also noticed: 3.9 +/- 1.5% (95% CI: 0.6-7.2); 0.671 +/- 0.02 vs 0.697 +/- 0.02 gr/cm2 (p < 0.05). Patients treated with transdermal and oral routes showed similar results. Percentage variations in LS BMD and FN BMD were positively correlated (r: 0.53; p < 0.05). Six patients were treated for 2 years; LS BMD continued to rise, the additional gain being 5.1 +/- 2.2% (p < 0.05), while a non significant increase in FN BMD was observed (7.5 +/- 3.5%; p = 0.06). In the early postmenopausal period, hormonal replacement therapy (HRT) produces either a stabilization or a slight increase (2-4%) in BMD. In contrast, a significant augmentation of bone mass (especially at the spine) seems to occur in osteopenic women when THR is administered in the late postmenopausal period. This suggests that HRT could be used for the prevention as well as for the treatment of postmenopausal osteoporosis. Further studies should be done to evaluate whether HRT reduces the incidence of osteoporotic fractures in elderly osteopenic women.
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PMID:[Effects of estrogen therapy on bone mass in postmenopausal women with osteopenia]. 872 70

Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were -2.1 +/- 1.3%, +2.8 +/- 1.5%, and -0.3 +/- 1.3% (mean +/- SEM), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were -5.9 +/- 2.1%, -3.8 +/- 1.2% and -1.0 +/- 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 +/- 2.3% every 6 months but did not stabilize femoral neck BMD (-3.5 +/- 1.4%). Fluoride increased lumbar BMD by 4.8 +/- 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (-0.3 +/- 1.3% and -1.0 +/- 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4-10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN.
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PMID:Follow-up of bone mineral density in 27 cases of anorexia nervosa. 898 Jan 62

Estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women and inhibits progression of coronary artery atherosclerosis in monkeys. Tamoxifen is a nonsteroidal compound with mixed estrogen agonist and antagonist properties. Its antagonist activity is useful in chemotherapy of breast cancer and may have protective effects on plasma lipid concentrations, but its effects on atherogenesis have not been defined. The goal of this study was to examine the effect of tamoxifen on plasma lipids, arterial and hepatic LDL metabolism, and progression of coronary artery atherosclerosis in surgically postmenopausal female monkeys. Thirty-five monkeys were fed an atherogenic diet containing 1.3 mg.kg-1.d-1 tamoxifen (equivalent to the usual dose of 20 mg/d given to women). Thirty-one monkeys were fed the same atherogenic diet with no tamoxifen. Ten monkeys from each treatment group were fed the test diets for 12 weeks to examine the short-term effects of tamoxifen on arterial LDL metabolism. The rest of the monkeys were fed the test diets for 3 years to study the long-term effects of tamoxifen on development of atherosclerosis. In the short term, tamoxifen inhibited the rate of arterial accumulation of LDL degradation products overall (P = .03) and decreased hepatic cholesterol content (P = .003). In the long term, tamoxifen increased plasma concentrations of triglycerides (0.60 +/- 0.67 versus 0.23 +/- 0.02 mmol/L, P = .001) and reduced average LDL molecular weight (5.3 +/- 0.2 versus 4.8 +/- 0.1 g/mumol, P = 0.004) but had no effects on plasma total, LDL, or HDL cholesterol concentrations. Coronary artery atherosclerosis (intimal area, mean +/- SEM) was 0.25 +/- 0.06 mm2 in control monkeys and 0.12 +/- 0.03 mm2 in tamoxifen-treated monkeys (P = .057). We conclude that tamoxifen has antiatherogenic effects that may be modulated in part through direct effects on arterial LDL metabolism.
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PMID:Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys. 908 97

Although osteoporosis is usually associated with women, 1 in 12 men in the UK have the disease, and a third of these cases are idiopathic. Estrogen is now known to be associated with bone loss in older men, but we found, previously, that levels of this hormone were normal in younger cases of male idiopathic osteoporosis (MIO) in the age range 33-61 years. We therefore hypothesized that their estrogen responses in bone might be defective, through impaired estrogen receptor-alpha (ER)-alpha expression. Consequently, in the present study, we compared expression of ER-alpha by indirect immunofluorescence, semiquantitative image analysis, and in situ reverse transcription-polymerase chain reaction in bone sections from MIO patients (33-56 years) (N = 7); age-matched control men (N = 7); and, for reference, ovarian steroid (OS)-replete (N = 7) and OS-deficient women (N = 6). In the control men, 23 +/- 6% (mean +/- SEM) of osteoblasts and 14 +/- 2% of osteocytes expressed ER-alpha protein, similar to OS-replete women. Although receptor expression decreased in OS-deficient women, the loss of ER-alpha protein in MIO patients was more severe (1 +/- 0.5% osteocytes, 2 +/- 1% osteoblasts expressed receptor); however, ER-alpha messenger RNA (mRNA) was still expressed in controls and MIO patients. Bone loss in these patients may be due to deficient ER-alpha protein expression.
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PMID:Preliminary evidence for impaired estrogen receptor-alpha protein expression in osteoblasts and osteocytes from men with idiopathic osteoporosis. 1077 80

Estrogen is a prominent stimulus to GH secretion throughout the human life span, albeit via neuroendocrine mechanisms that are incompletely defined. Here, we test the hypothesis that estradiol replacement in postmenopausal women enhances the responsiveness of the hypothalamo-pituitary unit to the GH-releasing effect of GH-releasing peptide-2 (GHRP-2). GHRP-2 is a potent and selective synthetic hexapeptide capable of activating an endogenous GHRP receptor/effector pathway, for which a (3)Ser-octanoylated 28-amino acid ligand was cloned recently. To examine this postulate, we studied 10 healthy estrogen-withdrawn postmenopausal women, who were given oral placebo or estrogen supplementation [1 mg micronized 17 beta-estradiol (E(2)) twice daily for 7-15 days] in a patient-blinded, prospective, randomized, and within-subject cross-over design. The GH-releasing actions of five semilogarithmically increasing doses of GHRP-2 (absolute range, 0.03-3 microg/kg by bolus iv infusion) vs. saline were evaluated by frequent blood sampling on separate days in the morning while fasting. Serum GH concentrations were determined in blood sampled every 10 min using an ultrasensitive chemiluminescence assay and analyzed by multiparameter deconvolution to calculate the summed mass of GH secreted during the 2-h interval after bolus GHRP-2 infusion. Logarithmically transformed secretory responses were compared across the different dosages of infused GHRP-2 by two-way repeated measures ANOVA. Estradiol replacement increased the global mean (+/-SEM) serum E(2) concentration from 15 +/- 0.8 to 470 +/- 17 pg/mL (55 +/- 2.9 to 1725 +/- 62 pmol/L; P = 0.004) and lowered insulin-like growth factor I levels by approximately 27% (P = 0.087). Administration of E(2) elevated the geometric mean basal (saline-infused) GH secretory burst mass by 2.1-fold (95% confidence interval, 1.4- to 3.1-fold) compared with placebo ingestion (geometric mean ratios; P < 0.001). E(2) exposure enhanced the efficacy of the highest GHRP-2 dose tested (3 microg/kg) by 2.1-fold (1.3- to 3.3-fold; P = 0.010). Compared with the effect of placebo and saline, E(2) combined with the highest dose of GHRP-2 stimulated GH secretory burst mass by a total of 31-fold (24- to 41-fold; P < 0.001). Random coefficient regression analysis of the relationship between the logarithm of GHRP-2 dose and GH secretory burst mass revealed that E(2) significantly augmented the amount of GH secreted per unit GHRP-2 dose (E(2), 16.6 +/- 1.8 slope units; placebo, 10.1 +/- 1.4 slope units; P = 0.03). Although the global mean endogenous GH half-life did not differ between the E(2) and placebo sessions (E(2), 18 +/- 0.6 min; placebo, 17 +/- 0.5 min), GH half-life varied directly with dose of GHRP-2 (and, hence, the mean serum GH concentration) in both the E(2) and placebo sessions (test of zero slope hypothesis, P = 0.0018). The deconvolved GH secretory burst peaked within 8-13 min of the bolus iv injection of GHRP-2, and this latency was not altered by E(2). Based on a mixed effects analysis of covariance model, GHRP-2 dose and E(2), but not the plasma insulin-like growth factor I concentration, determined the magnitude of the GH secretory response (P < 0.001). We conclude that short-term oral E(2) repletion in postmenopausal women selectively augments GH secretory pulse mass, enhances the steepness of the GHRP-2 dose-GH secretory response relationship (greater sensitivity), and heightens the maximal GH secretory response to the highest dose of GHRP-2 tested (greater efficacy). These data point to a facilitative interaction between E(2) and the GHRP receptor/effector pathway in driving the mass of GH secreted per burst.
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PMID:Short-term estradiol supplementation augments growth hormone (GH) secretory responsiveness to dose-varying GH-releasing peptide infusions in healthy postmenopausal women. 1115 8

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory dose of infused somatostatin by 13.5-fold, from 0.43 (0.38-0.48, 95% group statistical confidence intervals) (placebo) to 6.0 (5.2-7.0) (estradiol) microg/1.73 m(2)/h (P < 10(-4)), denoting muting of somatostatin's inhibitory potency. The latter inference was confirmed by a concomitant 4-fold decrease in the exponential steepness of the somatostatin inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs. 0.34 (0.62 to 0.26) (estradiol) slope units (P < 10(-4)). The foregoing effects were specific, because estrogen did not alter somatostatin's dose-dependent enhancement (P < 10(-4)) of the orderliness of GH release patterns, as quantitated via the approximate entropy regularity statistic. In summary, short-term replacement of estradiol to midfollicular phase levels in postmenopausal women selectively reduces the potency, but not the efficacy, of somatostatin's dose-dependent inhibition of GH release. Estrogen supplementation does not modify somatostatin's reciprocal enhancement of the quantifiable orderliness (approximate entropy) of the GH secretory process. Accordingly, we postulate that estradiol can facilitate pulsatile GH secretion, in part, by opposing the repressive actions of somatostatin.
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PMID:Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion. 1144 79

It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating estrogen. We studied the responsiveness of forearm resistance arteries to vasoconstrictor and vasodilator agents in 12 men (mean+/-SEM age, 68.7+/-2.6 years) rendered hypogonadal as a result of treatment for prostatic cancer, before and after 8 weeks of estrogen supplementation (estradiol valerate 1 mg daily; n=7) or placebo (n=5). Forearm blood flow was measured by venous occlusion plethysmography, and vasoactive agents were infused through a brachial artery cannula in doses that did not affect blood pressure or heart rate. Estrogen supplementation was well tolerated, with no adverse effects. After estrogen treatment, mean estradiol levels increased from <30 to 308+/-65 pmol/L, and both systolic and diastolic blood pressures were reduced. HDL cholesterol levels increased significantly, and vasoconstrictor responses to the NO synthase inhibitor N(G)-monomethyl-L-arginine (1, 2, 4 micromol/min) were enhanced. Vasoconstrictor responses to angiotensin II (8, 16, 32 ng/min) were markedly attenuated by estrogen treatment, as were vasoconstrictor responses to norepinephrine (25, 50, 100 ng/min). Estrogen did not alter the vasodilator responses to acetylcholine (9.25, 18.5, 37 microgram/min) or to the endothelium-independent agent sodium nitroprusside (1.6 microgram/min). Responses to all vasoactive agents were unchanged after administration of placebo. We conclude that low-dose estrogen supplementation in hypogonadal men is well tolerated, lowers blood pressure, and may affect vascular reactivity in a manner that is potentially beneficial, through several mechanisms, including enhancement of basal NO release and attenuation of vasoconstrictor responses to angiotensin II and norepinephrine. These findings suggest the need to consider a possible clinical role for estrogenic compounds in cardiovascular risk reduction in some groups of men.
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PMID:Low-dose estrogen supplementation improves vascular function in hypogonadal men. 1171 90


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