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Biomedical subjects

D L Loriaux

Publications and source records attributed to D L Loriaux.

At least 253 records · Page 14Linked to original sources
PubMed1983

Radioimmunoassay and metabolic clearance rate of catecholestrogens, 2-hydroxyestrone and 2-hydroxyestradiol in man.

Plasma levels of 2-hydroxyestrone (2-OHE1) and 2-hydroxyestradiol (2-OHE2) were determined by a new radioimmunoassay which employed a short Sephadex LH-20 column chromatography for the purification of samples and the antiserum to 2-hydroxyestrone-17-(O-carboxymethyl)oxime-BSA conjugate for assay. The plasma value was below the detection limit for the assay (approximately 15 pg/ml) in men and non-pregnant women, but rose 20-200 pg/ml during pregnancy in 2-OHE1 and around 15 pg/ml in the 3rd trimester of pregnancy in 2-OHE2. There was no significant difference of plasma 2-OHE1 level between normal pregnancy and toxemic pregnancy with hypertension, in the 3rd trimester. The plasma level was very low in all of three subjects with the placental dysfunction in toxemic pregnancy. The plasma metabolic clearance rate (MRCp) of 2-OHE1 and 2-OHE2 were determined in normal adults by two methods; infusion of unlabeled 2-OHE1 and 2-OHE2 to equilibrium with radioimmunoassay of their plasma levels, and infusion of [3H]-2-OHE1 and [3H]-2-OHE2 to equilibrium with measurement of chromatographically purified their tritium. The MCRs by the former and latter methods was 40-70 X 10(3) and 15-50 X 10(3) in 2-OHE1, and 18-29 X 10(3) and 12-14 X 10(3) l/day in 2-OHE2, respectively. The major plasma metabolite comigrated with 2-methoxy compounds to each catecholestrogen. The t1/2 of disappearance rate by the method of infusion of unlabeled compounds was approx. 45 s in 2-OHE1 and 90 s in 2-OHE2. When [3H]-2-OHE1 and [3H]-2-OHE2 were incubated with blood samples of adults, 2-methoxy compounds also rapidly formed. From these results it is concluded that the extremely high MCRp of 2-OHE1 and 2-OHE2 make it unlikely these compounds circulate peripherally except in pregnancy in levels sufficient to produce the physiological effects on estrogen receptors or catecholamines.

Adult↗
PubMed1983

The effects of estradiol and progesterone on rat ovarian 17-hydroxylase and 3 beta-hydroxysteroid dehydrogenase activities.

Testosterone biosynthesis by Leydig cells can be modulated by estradiol. This modulation appears to occur at the 17-hydroxylase and 17,20-desmolase stage. In this study we have examined the effects of estradiol and progesterone on the activities of the 17-hydroxylase (17-OH) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in rat ovarian tissue, to examine the hypothesis that estradiol may regulate these enzymes in the ovary as well as in the testis. Estradiol capsule implants produced a decrease in 17-OH activity (0.5 +/- 0.05 vs. 2.1 +/- 0.1 nmol/mg protein/min, mean +/- SEM, p less than 0.001), and an increase in 3 beta-HSD activity (15.5 +/- 0.9 vs 9.7 +/- 0.7 nmol/mg protein/min p less than 0.001). Progesterone injections produced a decrease in both 17-OH (0.9 +/- 0.1 vs. 2.3 +/- 0.2 p less than 0.005) and 3 beta-HSD (2.5 +/- .4 vs. 8.6 +/- 0.5; p less than 0.005) activities. We conclude that estradiol decreases 17-OH activity in the ovary as it does in the testis. This, coupled with an increase in 3 beta-HSD may explain the pre-ovulatory increase in progesterone seen in many species. Progesterone seems to decrease the steroidogenic activity of the ovarian tissue, perhaps offering an explanation for the gonadotropin resistance seen in corpus luteus bearing ovaries.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Androgen receptor characteristics in skin fibroblasts from men with pubertal macromastia.

Endocrine studies in men with pubertal macromastia (PM) have failed to reveal a hormonal abnormality to account for the disorder. As a result, it has been hypothesized that this form of gynecomastia may be a manifestation of a target organ abnormality. Because the syndromes of apparent androgen resistance, such as testicular feminization and Reifenstein's Syndrome, are associated with gynaecomastia, we examined skin fibroblasts cultured from men with pubertal macromastia for androgen receptor defects. We studied 12 men with PM and confirmed that plasma concentrations of testosterone, oestradiol, gonadotrophins, and prolactin, were all within the normal range; findings identical to those of a similar series of patients previously reported. Androgen receptor content (R0) and binding affinity (Kd) in cultured areolar and pubic skin fibroblasts were measured using a dispersed, whole cell assay. Nineteen areolar cell lines from the 12 patients with PM were compared with 4 areolar cell lines from three normal men and 9 areolar cell lines from nine normal women. There was no difference in the mean androgen receptor content (approximately 10 000 sites/cell) or binding affinity (approximately 1 nM) between the patients' fibroblasts and those of the normal subjects. Similarly, there were no differences in these parameters when pubic skin fibroblast androgen receptors were used for the comparison. We conclude that, although PM may yet be due to a defect in breast tissue sensitivity to androgen, the disorder cannot be explained by abnormalities in fibroblast androgen receptor number or affinity.

Adolescent↗
PubMed1983

Primary cortisol resistance: a family study.

Primary cortisol resistance is an autosomal disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of clinical stigmata of Cushing's syndrome. The proband with the severe form had hypertension and hypokalemic alkalosis. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the condition is revealed only by detailed examination of several parameters of cortisol secretion.

Adrenocortical Hyperfunction↗
PubMed1983

Developmental changes in neuroendocrine regulation of gonadotropin secretion in gonadal dysgenesis.

Patients with gonadal dysgenesis have a marked increase in gonadotropin levels at the age when puberty normally occurs. To determine whether this increase results from a change in the frequency or the amplitude of gonadotropin pulses, we measured the 24-h profile of plasma LH and FSH by RIA in 31 patients with gonadal dysgenesis, aged 2-20 yr. Gonadotropin pulses were defined as a rise from nadir to peak that exceeded 3 times the intraassay coefficient of variation. This criterion, based on an empirical study of RIA noise, reduced the rate of false positive peaks to less than 3-4/24 h. Using this criterion, peak amplitude increased significantly at the time of puberty for both LH and FSH (P less than 0.01). The overall frequency of gonadotropin pulses (the sum of the FSH peaks plus the LH peaks that occurred without a concomitant FSH peak), however, did not differ among prepubertal (12.7 +/- 1.8 peaks/24 h), pubertal aged (14.3 +/- 2.3 peaks/24 h), and adult patients (14.7 +/- 0.9 peaks/24 h). Thus, the increase in gonadotropin concentration in pubertal aged patients with gonadal dysgenesis appears to result primarily from an increase in gonadotropin peak amplitude rather than an increase in peak frequency.

Adolescent↗
PubMed1983

Effects of a growth hormone releasing factor in man.

The effects of the 44-amino acid growth hormone releasing factor (GRF-44) were tested in normal adult men and women. At a dose of 1 microgram/kg, intravenous boluses of GRF-44 stimulated prompt elevations of plasma GH, which in 5 men reached maximum levels of 34 +/- 28 (S.D.) ng/ml, and in 3 women in the mid-follicular phase, 53 +/- 10 ng/ml. The action of GRF was highly selective; there were no changes in plasma PRL, LH, FSH, TSH, or cortisol at this dose level. Side effects, mostly flushing and a sense of warmth of the face and chest, were mild and occurred only in a minority of subjects.

Adult↗
PubMed1983

Marijuana: interaction with the estrogen receptor.

Crude marijuana extract competed with estradiol for binding to the estrogen receptor of rat uterine cytosol. Condensed marijuana smoke also competed with estradiol for its receptor. Pure delta 9-tetrahydrocannabinol, however, did not interact with the estrogen receptor. Ten delta 9-tetrahydrocannabinol metabolites also failed to compete with estradiol for its receptor. Of several other common cannabinoids tested, only cannabidiol showed any estrogen receptor binding. This was evident only at very high concentrations of cannabidiol. Apigenin, the aglycone of a flavinoid phytoestrogen found in cannabis, displayed high affinity for the estrogen receptor. To assess the biological significance of these receptor data, estrogen activity was measured in vivo with the uterine growth bioassay, using immature rats. Cannabis extract in large doses exhibited neither estrogenic nor antiestrogenic effects. Thus, although estrogen receptor binding activity was observed in crude marijuana extract, marijuana smoke condensate and several known components of cannabis, direct estrogenic activity of cannabis extract could not be demonstrated in vivo.

Animals↗
PubMed1982

delta 1-11-oxa-11-deoxycortisol: a new antiglucocorticoid with activity in vivo.

A new steroid-like compound, delta 1-11-oxa-11-deoxycortisol, was tested in a one-week growth suppression, thymus suppression and adrenal weight suppression bioassay for possible glucocorticoid antagonist activity in vivo. We hypothesized that this compound would have antiglucocorticoid activity based on previous studies of 11-deoxycortisol and delta 1,9(11)-11-deoxycortisol, which were optimal glucocorticoid antagonists in vivo in adrenalectomized rats, but which lost antiglucocorticoid activity in intact animals, apparently due to adrenal 11 beta-hydroxylation. Thus, delta 1-11-oxa-11-deoxycortisol, a compound which cannot undergo 11 beta-hydroxylation, was synthesized and tested as an antiglucocorticoid. This analog had an affinity for the rat thymus glucocorticoid receptor similar to that of its parent compounds (Ki 0.9-3.1 x 10(-7) M). A dose of 1 mg/rat antagonized the effect of 15 microgram of dexamethasone in the growth suppression assay (p less than 0.05) and in the thymus suppression assay (p less than 0.06), but did not antagonize dexamethasone-induced adrenal weight suppression. delta 1-11-Oxa-11-deoxycortisol did not exhibit glucocorticoid activity in any of the three assays. These data suggest that delta 1-11-oxa-11-deoxycortisol may be a pure competitive antagonist of dexamethasone.

17-Hydroxycorticosteroids↗
PubMed1982

Ovarian steroidogenic enzyme activities during the rat estrous cycle.

We have correlated the concentrations of serum LH, estradiol and progesterone with the activities of 2 ovarian steroid biosynthetic enzymes during the rat estrous cycle. Ovarian 3 beta-hydroxysteroid dehydrogenase isomerase (3-beta HSD) activity decreased from 29 +/- 6 nmol/mg protein/min (mean +/- SEM) in diestrus, to 7 +/- 0.4 nmol/mg protein/min in late proestrus (p less than 0.005), and subsequently increased to 36 +/- 9 nmol/mg protein/min in metestrus (p less than 0.01). Ovarian 17-hydroxylase (17-OH) activity decreased from early to late proestrus (3.3 +/- 0.2 vs 2.2 +/- 0.2 nmol/mg protein/min, p less than 0.0025), and subsequently increased to 3.9 +/- 0.2 in metestrus (p less than 0.001). Serum LH, estradiol and progesterone peaked during proestrus, and reached a nadir during estrus. We conclude that the activities of 3-beta HSD and 17-OH in the rat ovary vary markedly during the estrous cycle. These changes may underlie the pattern of steroid secretion characteristic of this process.

Animals↗
PubMed1982

Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms.

The concentrations of total and protein-unbound plasma cortisol of New World monkeys are higher than those of Old World primates and prosimians. The urinary free-cortisol excretion also is increased markedly. However, there is no physiologic evidence of increased cortisol effect. These findings suggest end-organ resistance to glucocorticoids. This was confirmed by showing that the hypothalamic-pituitary adrenal axis is resistant to suppression by dexamethasone. To study this phenomenon, glucocorticoid receptors were examined in circulating mononuclear leukocytes and cultured skin fibroblasts from both New and Old World species. The receptor content is the same in all species, but the New World monkeys have a markedly decreased binding affinity for dexamethasone. Thus, the resistance of these species to the action of cortisol is due to the decreased binding affinity of the glucocorticoid receptor. This presumed mutation must have occurred after the bifurcation of Old and New World primates (approximately 60 x 10(6) yr ago) and before the diversion of the New World primates from each other (approximately 15 x 10(6) yr ago).

Animals↗
PubMed1982

Adrenal function in women with idiopathic acne.

The adrenal secretion of androgens were examined in 9 women (ages 19-39 yr) with postadolescent idiopathic acne and compared to age and sex-matched normal controls. Plasma dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta 4-delta), cortisol, 17-hydroxyprogesterone, 11-deoxycortisol, and testosterone were measured by radioimmunoassay in the basal state and during a 48 hr ACTH infusion. The mean plasma and time-integrated plasma levels of the 3 adrenal androgens in patients with acne were 15-25% higher than normal controls, but the groups were not significantly different (p greater than .05). The plasma testosterone values, on the other hand, were similar in both groups. In addition, cortisol, 11-deoxycortisol and 17-hydroxyprogesterone basal plasma values and responses to ACTH in patients with acne were similar to the normal control values. These findings suggest that adrenal androgen secretion is at most mildly elevated in patients with idiopathic acne and is unlikely to be the sole cause of acne since many patients without acne have similar hormone levels. Increased sensitivity of the sebaceous gland to androgens or increased local metabolism of androgen hormones in the skin to potent androgen metabolites may offer alternative mechanisms for the pathogenesis of this disorder.

Acne Vulgaris↗
PubMed1982

Primary cortisol resistance in man. A glucocorticoid receptor-mediated disease.

We have studied a man suspected of having primary cortisol resistance on the basis of high 24-h mean plasma cortisol levels (27.4 micrograms/dl) and no stigmata of Cushing's syndrome. His son had slightly elevated 24-h mean plasma cortisol levels (9.9 micrograms/dl; normal 7.52 micrograms/dl). Both had high plasma protein unbound cortisol and increased urinary free cortisol. Plasma ACTH concentration was high, and both were resistant to adrenal suppression by dexamethasone. The father appeared to have mineralocorticoid excess resulting in hypertension, hypokalemia, and metabolic alkalosis. This was found to be due to markedly elevated plasma levels of deoxycorticosterone and corticosterone. The son, who was normotensive, had mildly increased plasma corticosterone and normal deoxycorticosterone levels. To study the apparent end-organ resistance to cortisol, we examined the glucocorticoid receptor in the white cells and fibroblasts of these patients. In both tissues, using both whole cell and cytosol assays, the glucocorticoid receptor was found to have reduced affinity for dexamethasone. In the cytoxol assays, a reduced receptor number was found as well. We conclude that cortisol resistance is a rare familial syndrome owing to an abnormal glucocorticoid receptor with a decreased affinity for cortisol.

Adrenocortical Hyperfunction↗
PubMed1982

Rapid regression of fetal adrenal zone and absence of adrenal reticular zone in the marmoset.

Developmental changes in plasma dehydropiandrosterone (DHA) and in adrenal histology were studied in several marmoset species (Callithrix jacchus and Saguinus labiatus, nigricollis, and fuscicollis) to evaluate these primates as experimental models for the study of fetal adrenal zone regression. Newborn marmosets had a prominent fetal adrenal zone, plasma DHA levels above 1000 ng/dl, and plasma DHA sulfate (DHAS) levels of 140 micrograms/dl. The fetal zone regressed dramatically during the first week of life, paralleled by a marked decline in plasma DHA, the plasma DHA to cortisol ratio, and plasma DHAS. The adult marmoset, however, had no adrenal reticular zone and no evidence of adrenal DHA secretion; DHA levels in castrate adults were undetectable (less than 25 ng/dl). Thus, the marmoset represents the first example of a primate that has a regressing, DHA- and DHAS-secreting fetal adrenal zone but that does not subsequently develop a DHA-secreting adrenal reticular zone.

Adrenal Glands↗
PubMed1982

Radioimmunoassay and metabolism of the catechol estrogen 2-hydroxyestradiol.

Plasma levels of 2-hydroxyestradiol (2-OHE2) were measured using a new RIA procedure. Values were below the detection limit of the assay (less than 10 pg/ml), except in the third trimester of pregnancy, when they rose to approximately 15 pg/ml. The infusion of 130 microgram/h purified 2-OHE2 elevated its plasma concentration to 155 pg/ml, consistent with a plasma MCR (MCRp) of approximately 20,000 liters/day. The infusion of [3H] 2-OHE2 to equilibrium and chromatographic separation of the extracted plasma metabolites yielded an MCRp of about 13,000 liters/day; the major plasma metabolite comigrated with 2-methoxyestradiol, and [3H] xi-methoxyestrone was also formed. The MCRp, of 2-OHE2 is approximately half that of 2-hydroxyestrone (2-OHE1), but much higher than those of other steroids. As is true for 2-OHE1, the clearance of 2-OHE2 must occur primarily in the blood compartment. Together, the measured MCRp values and estrogen receptor affinities of 2-OHE2 and 2-OHE1 predict a relative potency for effects upon gonadotropin secretion which is close to that observed in vivo.

2-Methoxyestradiol↗
PubMed1982

Evaluation of pituitary gonadotropic function in men: value of luteinizing hormone-releasing hormone response versus basal luteinizing hormone level for discrimination of diagnosis.

We examined the serum LH response to LRH in 40 normal men and 38 men with various forms of gonadal dysfunction in an attempt to determine whether the LH response to LRH was more useful than the basal LH level alone for categorizing pathophysiological subgroups of gonadal dysfunction. The subgroups studied included hypogonadotropic hypogonadism, delayed puberty, idiopathic oligospermia, and primary hypogonadism. Log transformation of all values was done in order to normalize the data. Spearman's correlation analysis showed that increased basal LH was associated with increased incremental LH responses. However, our preliminary analysis of LRH response data suggested that the changes in LH were smaller in the secondary hypogonadal and delayed puberty groups then could be accounted for by the differences in basal LH level. Accordingly, we used various statistical techniques to test whether, and under what conditions, LRH testing provides information beyond that evident from examination of basal LH values. We found that the relationship between basal LH and the LH response to LRH differs in men with and without hypothalamic-pituitary dysfunction and that this difference can be exploited to improve the discrimination of men with pituitary hypogonadism from normals.

Adolescent↗