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D L Loriaux

Publications and source records attributed to D L Loriaux.

At least 289 records · Page 16Linked to original sources

Effects of catechol estrogen infusions upon gonadotropin and prolactin concentrations in men.

To study the effects of catechol estrogens upon gonadotropin secretion, 2-hydroxyestrone (2-OHE1) and 2-hydroxyestradiol (2-OHE2) were administered iv to young adult men in a range of doses for 4 days. Blood samples were obtained for plasma LH, FSH, and PRL at 20-min intervals for 6 h before and at the end of the infusion period. 2-OHE1 had no effect upon gonadotropins or PRL in doses up to 1.6 mg/day; at 3.2 and 6.6 mg/day, it produced a slight suppression of LH and FSH, with no change in PRL. 2-OHE2 was generally ineffective at 100 micrograms/day, but doses from 200-800 micrograms/day suppressed gonadotropins, without changes in PRL. These infusions elevated 2-OHE1 and 2-OHE2 plasma levels to values comparable to those measured in late pregnancy. There were no associated effects upon blood pressure and only minimal changes in urinary catecholamine excretion. No effects that could be interpreted as antiestrogenic were observed. These results are consistent with the hypothesis that circulating catechol estrogens behave as weak estrogens in men.

Adult↗

Andrenarche and its relationship to the onset of puberty.

During normal human sexual development the adrenal gland undergoes a maturational process, termed adrenarche, which results in increased adrenal secretion of androgens and estrogens. Adrenarche begins several years before the onset of gonadal maturation and correlates with the appearance of the adrenal reticular zone. In normal puberty, adrenarche and gonadarche (gonadal maturation) are closely linked, but in pathological situations adrenarche can occur without gonadarche, and gonadarche without adrenarche. Although the onset of puberty can be accelerated by elevated levels of adrenal androgens in patients with congenital adrenal hyperplasia, a normal onset of puberty in patients with premature adrenarche and primary adrenal insufficiency suggests that physiological levels of adrenal androgens do not exert a major influence on the timing of pubertal onset. Adrenal androgen levels and their developmental patterns differ markedly among species and, of the species so far examined, only the chimpanzee exhibits an adrenarche similar to that of man. Despite considerable investigation, the mechanisms underlying the initiation and maintenance of adrenarche are unknown.

Adolescent↗

Cerebellar involvement in multifocal eosinophilic granuloma: demonstration by computerized tomographic scanning.

Central nervous system involvement outside the hypothalamus or pituitary in multifocal eosinophilic granuloma (MEG) is unusual. Eleven patients with MEG have been examined with cranial computerized axial tomograms (CT). Four patients with moderate to severe cerebellar dysfunction, 3 of whom had no detectable lesions by other neuroradiological techniques, were found to have cerebellar abnormalities. All of the remaining 7 patients with normal neurological examinations had normal CT scans. Computerized axial tomography is a useful technique in the evaluation of patients with MEG and neurological impairment.

Adolescent↗

Low plasma levels of 2-hydroxyestrone are consistent with its rapid metabolic clearance.

Published plasma levels of the catechol estrogen 2-hydroxyestrone (2-OHE1) are comparable to those of estrone and estradiol. In light of the very high (40,000 L/d) metabolic clearance rate of 2-OHE1, these concentrations imply unreasonable production rates. We therefore re-examined plasma 2-OHE1 levels using a modified radioimmunoassay procedure. Plasma samples are extracted with ethyl acetate and passed over a short column of LH-20 Sephadex before equilibration with an antiserum directed against a 2-hydroxyestrone-17-(O-carboxymethyl)oxime-bovine serum albumin conjugate. Plasma 2-OHE1 concentrations are indistinguishable from blank (< 15 pg/ml) in men and non-pregnant women, but rise to approximately 200 pg/ml during pregnancy. These values for 2-OHE1 levels are consistent with the rapid metabolic clearance of this catechol estrogen.

Adolescent↗

Potential limitations of recrystallization for the definitive identification of radioactive steroids.

The usefulness of recrystallization in establishing the radiochemical purity of steroids is widely recognized, but the potential limitations of the technique have received little attention. The current study reports the failure of standard recrystallization procedures using methanol/water as the solvent pair to separate contaminating 14C-17-hydroxyprogesterone (17-hydroxy-4-pregnene-3, 20-dione) from 3H- and 14C-labeled 11-deoxycortisol (17,21-dihydroxy-4-pregnene-3,20-dione) despite ten serial crystallizations. The standard criteria of radiochemical purity were met despite gross impurity of the crystals as evidenced by thin layer chromatography. Thus, recrystallization may, under certain conditions, yield misleading results when employed as the only method for identifying radioactive steroids. These observations illustrate the importance of an optimal choice of solvent and crystallization conditions, and emphasize the need for confirmation by derivative formation and chromatography.

17-Hydroxycorticosteroids↗

A dispersed-whole cell method for the determination of androgen receptors in human skin fibroblasts.

A method is described for the determination of binding capacity (Ro) and dissociation constant (Kd) of androgen receptors in dispersed, whole, cultured human skin fibroblasts. The cells obtained from punch biopsies or operative specimens of skin, are grown to confluence in monolayers, harvested, washed, and dispersed in medium. Binding is assessed by incubating the cells with [3H]dihydrotestosterone (DHT) at 22 degrees C for one hour followed by washing, centrifugation and counting. Non-specific binding is determined by adding radioinert methyltrienolone (R1881). Scatchard plots are constructed using 6 concentration points; binding is expressed as sites/cell. The method is precise (Ro = 12,105 +/- 4305 (S.D.) sites/cell; Kd = 1.0 +/- 0.7 (S.D.) x 10(-9)M, n = 14 for one prepuce cell line) and independent of cell passage number. Binding is linear with respect to cell number and shows those characteristics commonly attributed to androgen receptors: high affinity, low binding capacity, saturable nuclear binding, androgen specificity, and an 8S peak in fibroblast cytosol using sucrose density gradients. Cell lines shown by other published methods to lack androgen receptors had no detectable DHT binding with this method. This assay technique has the advantages of simplicity, rapidity, and precision.

Breast Neoplasms↗

Testosterone-estradiol binding globulin binds to 2-methoxyestradiol with greater affinity than to testosterone.

This report describes the unexpected observation that testosterone-estradiol binding globulin (TeBG) binds 2-methoxyestradiol better than it binds either testosterone or 17 beta-estradiol. As determined by competitive displacement of 3H-testosterone from TeBG adsorbed onto a solid phase matrix of Con A-Sepharose, the relative binding activities of 2-methoxyestradiol, testosterone and 17 beta-estradiol for TeBG were 2.0, 1.0 and 0.32, respectively. In contrast, 2-methoxyestradiol, which is known to bind with low affinity to estrogen receptors, had only low affinity binding to the androgen receptor, as determined by competitive displacement of 3H-dihydrotestosterone using 64-24 rat mammary tumor cells. 2-Methoxyestradiol is the first example of a naturally occurring steroid which binds with high affinity to TeBG but with low affinity to both androgen and estrogen receptors.

2-Methoxyestradiol↗

Rapid metabolic clearance of the catechol estrogen 2-hydroxyestrone.

The plasma metabolic clearance rate (MCRp) of 2-hydroxyestrone was measured in normal young adults by two methods: infusion of unlabeled 2-OHE1 to equilibrium with radioimmunoassay of plasma 2-OHE1 levels, and infusion of [3H]2-OHE1 to equilibrium with measurement of chromatographically purified plasma [3H]2-OHE1. MCR's were 40--70,000 L/day and 15--50,000 L/day, respectively. This is the highest known MCR for a naturally occurring steroid. The only measurable plasma metabolite of [3H]2-OHE1 co-migrated with 2-methoxyestrone. When [3H]2-OHE1 was incubated with blood samples in vitro, [3H] xi-methoxyestrone was rapidly formed. Since this MCR is higher than cardiac output, clearance must occur primarily in the blood compartment, probably largely by the action of erythrocyte catechol-0-methyltransferase.

Adult↗

Effect of receptor occupancy on [3H]dexamethasone binding to circulating leukocytes.

To determine the effect of steroid occupancy of the glucocorticoid receptor on the measurement of total receptor concentration using Scatchard plot of [3H]dexamethasone (Dex) binding to circulating leukocytes, leukocytes were incubated with 10(-7)M cortisol or 10(-9)M Dex prior to [3H]Dex binding study. Total binding capacity calculated from Scatchard plot analysis of [3H]Dex binding was not significantly reduced after pre-incubation with cortisol. However, total binding capacity was significantly lower after pre-incubation with Dex. These data suggest that total glucocorticoid receptor concentration can be measured from a 3 h incubation of leukocytes obtained from untreated patients.

Animals↗

Timed 12-hour specimens in outpatient estriol monitoring.

Use of maternal urinary estriol excretion to monitor fetal status is often hampered by the difficulties of obtaining 24-hour specimens. Evidence is presented that timed, 12-hour overnight specimens may be substituted for the 24-hour specimens in certain patient groups. A simple non-refrigerated transport system which facilitates outpatient estriol monitoring is also described.

Ambulatory Care↗

H-Y antigen mosaicism in the gonad of a 46,XX true hermaphrodite.

To clarify the mechanism for the coexistence of ovarian and testicular tissue in the 46,XX true hermaphrodite, we studied a 20-year-old phenotypic male with gynecomastia and elevated serum concentrations of estradiol in whom an ovotestis was discovered upon scrotal exploration. Y chromosomal material could not be detected by fluorescent Y-body analysis or Giemsa-banding technics in cells cultured from peripheral blood, breast or forearm skin or the ovarian or testicular portions of the ovotestis. However, serologic testing, using the sperm cytotoxicity assay, revealed that cells cultured from the testicular portion of the ovotestis were H-Y antigen positive whereas cells cultured from the ovarian portion were H-Y antigen negative. These observations indicate that the ovotestis arises from an H-Y+/H-Y- mosaic primordium.

Adult↗