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Biomedical subjects

D L Loriaux

Publications and source records attributed to D L Loriaux.

At least 109 records · Page 6Linked to original sources
PubMed1987

Adrenal 11-hydroxylase activity in a hypercortisolemic New World primate: adaptive intra-adrenal changes.

The squirrel monkey, a representative New World primate, has high plasma cortisol and aldosterone concentrations when compared to Old World primates. We measured adrenal mitochondrial 11-hydroxylase (11-OHase) activity in squirrel monkeys and in two representative Old World species (cynomolgus and rhesus macaques) in an effort to explain these elevated plasma glucocorticoid and mineralocorticoid levels. The activity of 11-OHase was 5-fold higher in the squirrel monkey than in the Old World species tested. Calculated 11-OHase Vmax was different in the squirrel monkey and the cynomolgus. However, the Km values were similar in the New World primate when compared to cynomolgus. The ability of metyrapone to block 11-OHase was less in the former than in the latter. The data are consistent with the hypothesis that the squirrel monkey adrenal cortex possesses an increased number of 11-hydroxylase enzyme units compared to that of Old World primate species, and is therefore more efficient in producing cortisol. This difference in 11-OHase activity in the squirrel monkey, in addition to other previously reported adrenal steroidogenic enzyme alterations, may be adaptive in nature, favoring increased cortisol and aldosterone production in this and possibly other New World primate species.

Adaptation, Physiological↗
PubMed1987

Developmental processes in early adolescence. Relations among chronologic age, pubertal stage, height, weight, and serum levels of gonadotropins, sex steroids, and adrenal androgens.

Cross-sectional data are presented on 108 young adolescents (56 boys, 52 girls), ages 9 to 14 years. The measures were: for all subjects, pubertal stage (Tanner criteria for genital/breast and pubic hair stage); height and weight; serum hormone concentrations for gonadotropins (luteinizing hormone and follicle-stimulating hormone), sex steroids (testosterone, estradiol, and the computed testosterone to estradiol ratio), adrenal androgens (dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione), and testosterone-estradiol binding globulin. In addition, testicular volume for boys and menarchial status for girls are reported. The study goal was to provide interrelations among these measures, based on the same sample, and examine their interchangeability. Results suggest that it would be reasonable to compare research across as well as within studies based on different markers. Multiple regression analysis showed that the strongest hormone correlates of pubertal development were androgen levels (primarily testosterone in boys and primarily dehydroepiandrosterone sulphate and androstenedione in girls). Estradiol level in girls was the strongest correlate only for menarchial status. Level of testosterone-estradiol binding globulin, which was lower at successive pubertal stages for boys and showed no consistent differences for girls, may be a useful measure for studying the developmental processes and gender differences during puberty.

Adolescent↗
PubMed1987

Effect of the antiprogestin RU486 on human ovarian steroidogenesis.

Previous studies in the authors' laboratory suggest that the antiprogestin RU486 may directly affect human ovarian progesterone production. The possibility that this compound could affect other steps in human ovarian steroidogenesis was examined by studying its effects on estrogen production in cultured human granulosa cells and on human ovarian aromatase (AR) and 17-hydroxylase (17-OH) activities in vitro. RU486 had no effect on media estradiol (E2) levels as measured by radioimmunoassay (RIA) over a 24-hour incubation period. Furthermore, no effect on ovarian AR activity occurred at concentrations of RU486 100 times substrate. However, a dose-dependent decrease in the activity of 17-OH was observed with increasing amounts of drug. RU486 decreased 17-OH activity by 12 and 29% below that of basal activity at concentrations equal to and ten times substrate. At 50- and 100-fold excess, RU486 further decreased 17-OH activity by 42 (P less than 0.01) and 48% (P less than 0.005). In conclusion, RU486 directly inhibits human ovarian 17-OH activity, but does not affect AR activity or E2 production in vitro. Clinically observed decreases in serum E2 levels may be due to inhibition of enzymatic steps proximal to E2 synthesis. These findings support the authors' previous observations suggesting that RU486 has a direct affect on human ovarian steroidogenesis.

Adult↗
PubMed1987

Growth hormone secretory dynamics in children with precocious puberty.

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.

Body Height↗
PubMed1987

Developmental processes in early adolescence: relationships between adolescent adjustment problems and chronologic age, pubertal stage, and puberty-related serum hormone levels.

Relations between adolescent psychosocial adjustment problems and markers of biologic development, including chronologic age, pubertal status, and serum hormone levels, were examined in 56 normal boys and 52 normal girls, ages 9 to 14 years. Adolescent psychosocial adjustment was assessed by adolescent self-ratings of various aspects of self-image (Offer Self-Image Questionnaire for Adolescents) and parent ratings of adolescent behavior problems (Child Behavior Checklist). The pubertal status measure used in the analyses was Tanner genital stage for boys and Tanner breast stage for girls. The hormone measures, determined by radioimmunoassay, were serum levels of gonadotropins (luteinizing hormone and follicle stimulating hormone), sex steroids (testosterone and estradiol), and adrenal androgens (dehydroepiandrosterone and its sulfate, and androstenedione). The testosterone/estradiol ratio also was computed. Overall, findings were stronger, more consistent, and more generalized for boys than for girls. For boys, adjustment problems typically were associated with a multivariate profile that may be characteristic for later maturers: relatively low sex steroid levels, or lower pubertal stage, and relatively high adrenal androgen (androstenedione) levels, frequently in conjunction with higher chronologic age. Univariate relations predominated for girls; that is, associated with adjustment problems for girls were relatively high levels of gonadotropins, relatively low levels of dehydroepiandrosterone sulfate, and relatively high levels of androstenedione on their own or in conjunction with lower pubertal stage. Higher levels of androstenedione, a steroid particularly responsive to stress, were associated with adjustment problems in both boys and girls. This relation may reflect the stress of later maturation, which could result from environmental factors, such as adolescent self-comparisons with same-age peers, or endogenous effects of hormones.

Adolescent↗
PubMed1987

New evidence for a direct effect of prolactin on rat adrenal steroidogenesis.

The direct effect of prolactin on rat adrenal steroidogenic enzyme activity was evaluated by measuring plasma and adrenal cytosol steroid levels and adrenal microsomal 3B-hydroxysteroid dehydrogenase/isomerase (3B-HSD), 21 hydroxylase (21-OHase) and mitochondrial 11-hydroxylase (11-OHase) after in vivo administration of purified rat prolactin (rPRL) to adult, female Sprague-Dawley rats. Animals were ovariectomized, hypophysectomized and replaced with ACTH. Two days after surgery rPRL was administered i.p. at doses of 1.0, 10.0 and 100.0 micrograms (micrograms) every 4 hours for 5 days to experimental animals. Control rats received vehicle injections. All rats were sacrificed by decapitation and blood and adrenal glands collected. The adrenals were pooled into each rPRL dose group and mitochondria, microsomes and cytosol prepared from each pool. The activities of 3B-HSD, 21-OHase and 11-OHase were measured using as substrates 14C-dehydroepiandrosterone, 14C-progesterone and 14C-deoxycorticosterone, respectively. Plasma prolactin levels rose from 9.9 +/- 2.5 ng/ml in the control animals to 166.0 +/- 37.7 ng/ml (p less than 0.001) in the 100 micrograms rPRL dose group. Plasma corticosterone levels were not statistically different in the experimental groups when compared to controls. However, adrenal weight was increased in the high dose rPRL group (34.9 +/- 0.9 mg vs 41.9 +/- 1.2 mg, p less than 0.025). Hyperprolactinemia did not influence microsomal 3B-HSD or mitochondrial 11-OHase activities but was associated with a dose dependent decrease in microsomal 21-OHase activity when compared to controls (p less than 0.001). Adrenal cytosol progesterone levels increased with increasing rPRL dose consistent with a 21-OHase block during hyperprolactinemia. These data suggest that prolactin has a direct effect on rat adrenal 21-OHase in vivo.

Adrenal Cortex↗
PubMed1987

Cushing syndrome: pituitary CT scanning.

Proper treatment of patients with Cushing syndrome depends on knowledge of whether the condition derives from a pituitary or adrenal adenoma or an ectopic tumor that secretes adrenocorticotropic hormone (ACTH). Fifty-seven patients with Cushing syndrome were prospectively evaluated to determine whether computed tomography (CT) of the pituitary gland is useful in diagnosing or excluding an ACTH-producing adenoma and in predicting the site of the adenoma within the pituitary gland. Findings on CT scans were normal in 35 of 50 patients with surgically confirmed Cushing disease and in seven patients with ectopic ACTH-producing tumors. Of the 15 patients with Cushing disease for whom CT results were abnormal, eight had macroadenomas and seven had microadenomas. This study demonstrates a low sensitivity (30%) and low diagnostic accuracy (39%) of CT in the detection of ACTH-producing pituitary tumors and indicates the need for alternative methods of confirming the pituitary origin of excessive ACTH secretion in most patients.

Adenoma↗
PubMed1987

Identification of ACTH-producing intrathoracic tumors by measuring ACTH levels in aspirated specimens.

Three patients with Cushing syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production underwent direct 22-gauge needle aspiration of bronchial (two cases) and mediastinal (one case) carcinoid tumors. High levels of ACTH were measured in all three tumors. This technique permits absolute identification of an ectopic source of ACTH before surgery.

ACTH Syndrome, Ectopic↗
PubMed1987

Pituitary adenomas in patients with Cushing disease: initial experience with Gd-DTPA-enhanced MR imaging.

To assess the role of magnetic resonance imaging in the evaluation of adrenocorticotropic-hormone (ACTH)-producing pituitary adenomas, and the effect of intravenously administered gadolinium-diethylenetriaminepentaacetic acid (DTPA) on lesion/pituitary contrast, imaging was performed in 13 patients with clinical and chemical evidence of Cushing disease. Images were obtained at 0.5 T before and after the injection of Gd-DTPA (0.1 mmol/kg). Lesions were identified in eight of 12 precontrast and ten of 12 postcontrast studies. In these 12 patients adenomas were found at transsphenoidal surgery. The other patient, with normal images, was found to have an ectopic source of ACTH. Coronal images corresponded remarkably well with the neurosurgeon's intraoperative findings. Serial T1-weighted images disclosed early enhancement of the pituitary gland and delayed enhancement of the cystic adenomas. The discrepancy in times to peak enhancement accounted for improved lesion/pituitary contrast in some early images and for reversal or diminution of lesion/pituitary contrast in later images.

ACTH Syndrome, Ectopic↗
PubMed1987

Effect of continuous somatostatin and growth hormone-releasing hormone (GHRH) infusions on the subsequent growth hormone (GH) response to GHRH. Evidence for somatotroph desensitization independent of GH pool depletion.

Continuous infusions of growth hormone-releasing hormone (GHRH) attenuate the subsequent growth hormone (GH) response to GHRH. To test whether this phenomenon can occur in the absence of GH pool depletion, we examined the effects of continuous infusions of 10 nM GHRH and of 10 nM somatostatin (SRIH), separately or in combination, on dispersed, perifused rat anterior pituitary cells. Columns of these cells were given either GHRH alone for 5 h, GHRH and SRIH together for 3 h followed by GHRH alone, or SRIH alone for 3 h followed by GHRH or medium. SRIH blunted both basal GH release and the GH response to GHRH, without affecting the subsequent GH responses to GHRH. The GHRH infusions attenuated the subsequent GH response to GHRH, even when GH release was initially prevented by the concurrent infusion of SRIH. Furthermore, the degree of attenuation was similar in the presence or absence of SRIH, suggesting that pool depletion plays little role in the desensitization process under these experimental conditions. The results are consistent with the hypothesis that a short-term infusion of GHRH leads to attenuation of the GH response in rat anterior pituitary cells primarily through receptor effects rather than through GH pool depletion.

Animals↗
PubMed1987

Effect of bromocriptine on affect and libido in hyperprolactinemia.

Six women with primary hyperprolactinemia (mean prolactin level, 50 ng/ml) were matched with six normal women on eight factors influencing life style. Observers blind to endocrine status followed the subjects weekly for 10 weeks. Patients took bromocriptine, 2.5 mg twice daily, or placebo in a randomized double-blind sequence with crossover at 5 weeks. The mean Hamilton score for the patients was compatible with mild depression and higher than that for normal subjects during placebo but not during bromocriptine treatment. Libido was similar in both groups during placebo and bromocriptine. The mean number of orgasms reported per day was lower in patients than in normal subjects during both treatment conditions, although one patient reported orgasms during drug treatment only. Hyperprolactinemia in women may be associated with mild depression and a decrease in orgasmic frequency.

Adult↗
PubMed1987

The relationship of saline-induced changes in vasopressin secretion to basal and corticotropin-releasing hormone-stimulated adrenocorticotropin and cortisol secretion in man.

To investigate the effect of endogenous arginine vasopressin (AVP) on ACTH secretion, normal subjects were given infusions of either hypertonic saline (HS) or isotonic saline (NS) combined with human corticotropin-releasing hormone (CRH) or placebo. Basal plasma AVP was 2.3 +/- 0.3 (+/- SE) pg/ml, did not change with NS treatment, and rose to 5.4 +/- 0.6 pg/ml during HS infusion (P less than 0.01). Both basal and CRH-stimulated plasma ACTH and cortisol concentrations increased during HS infusion. Peak plasma ACTH and cortisol levels were 11.4 +/- 1.5 pg/ml and 8.6 +/- 0.8 micrograms/dl, respectively, during the HS (plus placebo) infusion. During the NS (plus placebo) infusion, plasma ACTH and cortisol gradually declined to 6.8 +/- 0.5 pg/ml and 2.6 +/- 0.4 micrograms/dl. The timing of the rise in ACTH during the HS infusion paralleled the rise in AVP. When an iv dose of 1 microgram/kg CRH was administered during the saline infusions, peak plasma ACTH and cortisol levels were 27.7 +/- 6.3 pg/ml and 17.5 +/- 1.0 micrograms/dl, respectively, during the HS infusion and 15.6 +/- 1.7 pg/ml and 13.4 +/- 1.2 micrograms/dl during the NS infusion. When the areas under the hormone response curves were compared, CRH stimulated ACTH and cortisol secretion to a greater extent than did HS (P less than 0.05). The hormonal stimulation due to combined CRH and hypertonic saline was greater than that attributable to either factor alone (P less than 0.025), but was not different than the sum of the effects of the individual factors. These results indicate that increases in endogenous AVP produced by HS are associated with increases in both basal and CRH-stimulated ACTH and cortisol release. The effect of HS appears to be additive to but not consistently synergistic with the effect of CRH.

Adrenocorticotropic Hormone↗
PubMed1987

The effect of mevinolin on steroidogenesis in patients with defects in the low density lipoprotein receptor pathway.

Adrenal steroidogenesis is dependent upon cholesterol derived from both de novo biosynthesis and uptake of plasma lipoproteins through the low density lipoprotein (LDL) receptor pathway. Recent studies have demonstrated that patients homozygous for familial hypercholesterolemia have a mild impairment in cortisol secretion during maximal ACTH stimulation. Mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, has been used clinically to inhibit de novo cholesterol synthesis in patients with familial hypercholesterolemia. In this study we examined hypothalamic-pituitary-adrenal function in seven patients with defects in the LDL receptor pathway, both before and during treatment with oral mevinolin (20 mg, twice a day), to assess whether inhibition of cholesterol synthesis influences steroidogenesis under basal conditions and in response to ovine CRH and exogenous ACTH. Two months after initiation of therapy, high density lipoprotein cholesterol levels were significantly elevated, and LDL cholesterol levels were reduced, although not normalized. Basal and ovine CRH-stimulated adrenocortical function were normal in all patients both before and during therapy. Plateau plasma cortisol concentrations achieved during maximal ACTH stimulation were lower than those in control subjects in all patients both before and during therapy. All patients, however, had an approximately 3-fold increase over basal values. These results suggest that treatment of patients with defects in the LDL receptor pathway with mevinolin improves the plasma lipid profile and does not result in adrenal dysfunction or further exacerbation of the mild impairment of adrenal function during maximal ACTH stimulation.

Adrenal Cortex↗
PubMed1987

Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress.

We studied the responses of plasma CRH, ACTH, cortisol, norepinephrine, epinephrine, and renin activity in 11 patients undergoing parathyroid or thyroid surgery after identical preoperative sedation and during isoflurane (Forane) anesthesia. During surgical exploration, plasma CRH levels [10 +/- 2 (+/- SEM) pg/mL] remained at basal (unstimulated) levels, and plasma ACTH (11.5 +/- 1.4 pg/mL), cortisol (24 +/- 4 micrograms/dL), and epinephrine (35 +/- 10 pg/mL) concentrations remained within their normal morning ranges. The majority of the patients had no evidence of pulsatile ACTH secretion during the operation, but, rather, secreted ACTH and cortisol continuously. There was a small elevation of plasma norepinephrine and PRA which was associated with a small increase in heart rate and decrease in blood pressure. Anesthesia reversal, endotrachial extubation, and the early recovery period were associated with marked mean peak increases in plasma ACTH (173 +/- 45 pg/mL), cortisol (35 +/- 6 micrograms/dL), and epinephrine (220 +/- 56 pg/mL) and the return of plasma norepinephrine and PRA to basal levels. All hormones returned to basal levels by the first post-operative day. The data suggest that with modern anesthetic techniques patients undergoing neck surgery had mildly elevated plasma ACTH, cortisol, and epinephrine levels. Glucocorticoid secretion during the operation was maintained primarily by continuous rather than pulsatile ACTH secretion. The immediate postoperative period was associated with profound elevations of plasma ACTH, cortisol, and epinephrine. The major determinant of ACTH, cortisol, and epinephrine secretion was anesthesia reversal and recovery and not surgical trauma.

Adrenocorticotropic Hormone↗
PubMed1987

Dissociation of adrenarche and gonadarche in precocious puberty and in isolated hypogonadotropic hypogonadism.

Adrenarche is a developmental change of the adrenal gland that results in increased secretion of adrenal androgens. This maturational process generally begins several years before activation of the hypothalamic-pituitary-gonadal axis (gonadarche). To study further the relationship between adrenarche and gonadarche, we examined adrenarche in patients with precocious puberty and in patients with isolated hypogonadotropic hypogonadism. Plasma dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, and cortisol were measured basally and during an infusion of ACTH in 50 children with precocious puberty, 5 patients with isolated hypogonadotropic hypogonadism, 7 preadrenarchal children with constitutional short stature, 44 normal pubertal children, and 40 normal adults. Children with precocious puberty did not have a corresponding advance in the timing of adrenarche. Their basal and ACTH-stimulated adrenal androgen levels were markedly lower than those of normal children matched for pubertal stage (P less than 0.05) and were only slightly greater than those reported for normal children of the same age. Similarly, patients with isolated hypogonadotropic hypogonadism and delayed puberty had no corresponding delay of adrenarche. Their adrenal androgen levels were appropriate for chronological age. Thus, these data provide further support for the hypothesis that adrenarche and gonadarche are independent maturational events controlled by separate mechanisms.

Adolescent↗
PubMed1987

Evidence for Leydig cell dysfunction in infertile men with a selective increase in plasma follicle-stimulating hormone.

Recent studies in acutely castrated males of several species have demonstrated that testosterone (T) alone, given in doses that produce normal plasma T levels, can maintain normal plasma FSH and LH levels. This suggests that a nonsteroidal factor from the seminiferous tubule is not required to regulate FSH release, and raises the possibility that Leydig cell function may not be fully normal in oligo- or azoospermic men with increased plasma FSH levels. To clarify this, we studied T production rates in 11 sexually mature, infertile, but otherwise healthy men who had increased plasma FSH and normal plasma LH, T, and estradiol levels and in 9 normal men. Although individual plasma T and LH levels in the infertile men were within the normal ranges, the mean plasma T level of the infertile men was significantly lower (P less than 0.002), and the mean plasma LH level was significantly higher (P less than 0.002) than values in the normal men. The infertile men also had significantly lower plasma free T concentrations (P less than 0.005), while sex hormone-binding globulin and estradiol levels were similar to those of the normal men. The production rate of T in the infertile men was half that in the normal men (P less than 0.001). We conclude that T production is significantly reduced in infertile men who have a selective increase in plasma FSH. Because of the known role of Leydig cell sex steroids in the negative feedback control of FSH, this finding may explain the elevated plasma FSH concentrations characteristic of men with germ cell loss without the need to postulate a deficiency of a separate seminiferous tubule factor.

Adolescent↗