Secretagogue type, sex-steroid milieu, and abdominal visceral adiposity individually determine secretagogue-stimulated cortisol secretion

DesignWhile androgens and estrogens control glucocorticoid secretion in animal models, how the sex-steroid milieu determines cortisol secretion in humans is less clear. To address this issue, cortisol was measured in archival sera obtained at 10-min intervals for 5 h in 42 healthy men administered double placebo, placebo and testosterone, testosterone and dutasteride (to block 5α-reductases type I and type II), or testosterone and anastrozole (to block aromatase) in a double-blind, placebo-controlled, prospectively randomized design.MethodsSubjects received i.v. injection of saline, GHRH, GH-releasing peptide-2 (GHRP-2), somatostatin (SS), and GHRP-2/GHRH/l-arginine (triple stimulus) each on separate mornings fasting. Outcomes comprised cortisol concentrations, pulsatile cortisol secretion, and relationships with age or abdominal visceral fat (AVF).ResultsBy ANCOVA, baseline (saline-infused) cortisol concentrations (nmol/l) did not differ among the sex-steroid milieus (overall mean 364±14). In contrast, stimulated peak cortisol concentrations were strongly determined by secretagogue type (P<0.001) as follows: triple stimulus (868±27)>GHRP-2 (616±42)>saline=SS=GHRH (grand mean 420±21). After GHRP-2 injection, pulsatile cortisol secretion increased with age (R2=0.16,P=0.012). After the triple stimulus, pulsatile cortisol secretion correlated i) inversely with serum 5α-dihydrotestosterone (DHT) concentrations (R2=0.53,P=0.026) and ii) directly with computerized tomography-estimated AVF (R2=0.11,P=0.038).ConclusionAge, DHT concentrations, AVF, and secretagogue type influence pulsatile cortisol secretion at least in men. Further studies should be performed to assess ACTH secretion and native ghrelin action in defined sex-steroid milieus.

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Cholinergic Influences on Use-Dependent Plasticity

Journal of Neurophysiology ◽

10.1152/jn.00279.2001 ◽

2002 ◽

Vol 87 (1) ◽

pp. 166-171 ◽

Cited By ~ 65

Author(s):

L. Sawaki ◽

B. Boroojerdi ◽

A. Kaelin-Lang ◽

A. H. Burstein ◽

C. M. Bütefisch ◽

...

Keyword(s):

Receptor Antagonist ◽

Motor System ◽

Global Changes ◽

Double Blind ◽

Double Blind Placebo ◽

Corticomotor Excitability ◽

Dependent Plasticity ◽

Motor Practice ◽

Randomized Design ◽

Human Motor

Motor practice elicits use-dependent plasticity in humans as well as in animals. Given the influence of cholinergic neurotransmission on learning and memory processes, we evaluated the effects of scopolamine (a muscarinic receptor antagonist) on use-dependent plasticity and corticomotor excitability in a double-blind placebo-controlled randomized design study. Use-dependent plasticity was substantially attenuated by scopolamine in the absence of global changes in corticomotor excitability. These results identify a facilitatory role for cholinergic influences in use-dependent plasticity in the human motor system.

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A randomized, double-blind, placebo-controlled study of the efficacy and tolerability of policosanol in adolescents with type II hypercholesterolemia

Current Therapeutic Research ◽

10.1016/s0011-393x(02)80033-9 ◽

2002 ◽

Vol 63 (4) ◽

pp. 286-303 ◽

Cited By ~ 10

Author(s):

Gladys Castaño ◽

Rosa Más ◽

Lilia Fernández ◽

José Illnait ◽

Eric Hernández ◽

...

Keyword(s):

Controlled Study ◽

Type Ii ◽

Double Blind ◽

Double Blind Placebo

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Pharmacokinetics, pharmacodynamics, and safety of subcutaneous anifrolumab in patients with systemic lupus erythematosus, active skin disease, and high type I interferon gene signature: a multicentre, randomised, double-blind, placebo-controlled, phase 2 study

The Lancet Rheumatology ◽

10.1016/s2665-9913(20)30342-8 ◽

2020 ◽

Author(s):

Ian N Bruce ◽

Alireza Nami ◽

Erik Schwetje ◽

M Edward Pierson ◽

Tomas Rouse ◽

...

Keyword(s):

Lupus Erythematosus ◽

Type I Interferon ◽

Gene Signature ◽

Type I ◽

Phase 2 ◽

Double Blind ◽

High Type ◽

Double Blind Placebo ◽

Phase 2 Study ◽

Interferon Gene

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Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers

Journal of the International Society of Sports Nutrition ◽

10.1186/1550-2783-10-48 ◽

2013 ◽

Vol 10 (1) ◽

pp. 48 ◽

Cited By ~ 17

Author(s):

James P Lugo ◽

Zainulabedin M Saiyed ◽

Francis C Lau ◽

Jhanna Pamela L Molina ◽

Michael N Pakdaman ◽

...

Keyword(s):

Healthy Volunteers ◽

Type Ii Collagen ◽

Controlled Study ◽

Type Ii ◽

Double Blind ◽

Double Blind Placebo ◽

Undenatured Type Ii Collagen

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Coated-tube radioimmunoassay for C-telopeptides of type I collagen to assess bone resorption

Clinical Chemistry ◽

10.1093/clinchem/42.10.1639 ◽

1996 ◽

Vol 42 (10) ◽

pp. 1639-1644 ◽

Cited By ~ 41

Author(s):

M Bonde ◽

C Fledelius ◽

P Qvist ◽

C Christiansen

Keyword(s):

Bone Resorption ◽

Postmenopausal Women ◽

Type I Collagen ◽

Premenopausal Women ◽

Type I ◽

Double Blind ◽

Double Blind Placebo ◽

Analytical Recovery ◽

Controlled Clinical Study ◽

Different Doses

Abstract We present a coated-tube RIA that is useful for assessment of bone resorption. The assay uses a monoclonal antibody raised against a linear 8-amino-acid sequence (EKAHDGGR) derived from the C-telopeptides of type I collagen. Within-run and total CVs were 4.4% and 5.3-6.2%, respectively, at concentrations of 1-7 mg/L (n = 4-20). Analytical recovery was 98% +/- 8% and dilution 97% +/- 7%. Values obtained in a group of 36 premenopausal women were 227 +/- 89.6 mg/mol creatinine. In a group of 141 postmenopausal women, the values obtained were 429 +/- 225 mg/mol creatinine, a highly significant increase of 89% (P <0.001) over the premenopausal value. In a double-blind placebo-controlled clinical study of these postmenopausal women receiving five different doses of a bisphosphonate, a significant decrease of RIA-measured C-telopeptide values was seen in all bisphosphonate-treated groups, after just 3 months. Values in urine samples from postmenopausal women assayed with the RIA (gamma) and the CrossLaps(TM) ELISA (x) agreed well: slope = 0.98 (95% confidence interval, 0.94-1.01), intercept = 0.34 (0.25-0.43) mg/L, and Sylx = 0.93 mg/L (n = 678). We conclude that this RIA represents a valuable tool for assessing bone resorption.

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Two multi-center, double-blind, placebo-controlled studies of efficacy and safety of acarbose treatment of type I diabetes

New Aspects in Diabetes ◽

10.1515/9783110859447-024 ◽

1992 ◽

pp. 238-238

Author(s):

P. Holander ◽

R. F. Coniff

Keyword(s):

Type I Diabetes ◽

Type I ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo ◽

Acarbose Treatment

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Enhanced circadian ACTH release in obese premenopausal women: reversal by short-term acipimox treatment

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00254.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. E848-E856 ◽

Cited By ~ 17

Author(s):

Petra Kok ◽

Simon W. Kok ◽

Madelon M. Buijs ◽

Jos J. M. Westenberg ◽

Ferdinand Roelfsema ◽

...

Keyword(s):

Hpa Axis ◽

Experimental Studies ◽

Premenopausal Women ◽

Secretory Activity ◽

Cortisol Secretion ◽

Obese Women ◽

Acth Secretion ◽

Double Blind ◽

Deconvolution Analysis ◽

Acth Release

Several studies suggest that the hypothalamo-pituitary-adrenal (HPA) axis is exceedingly active in obese individuals. Experimental studies show that circulating free fatty acids (FFAs) promote the secretory activity of the HPA axis and that human obesity is associated with high circulating FFAs. We hypothesized that HPA axis activity is enhanced and that lowering of circulating FFAs by acipimox would reduce spontaneous secretion of the HPA hormonal ensemble in obese humans. To evaluate these hypotheses, diurnal ACTH and cortisol secretion was studied in 11 obese and 9 lean premenopausal women (body mass index: obese 33.5 ± 0.9 vs. lean 21.2 ± 0.6 kg/m2, P < 0.001) in the early follicular stage of their menstrual cycle. Obese women were randomly assigned to treatment with either acipimox (inhibitor of lipolysis, 250 mg orally four times daily) or placebo in a double-blind crossover design, starting one day before admission until the end of the blood-sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of plasma ACTH and cortisol concentrations. ACTH and cortisol secretion rates were estimated by multiparameter deconvolution analysis. Daily ACTH secretion was substantially higher in obese than in lean women (7,950 ± 1,212 vs. 2,808 ± 329 ng/24 h, P = 0.002), whereas cortisol was not altered (obese 36,362 ± 5,639 vs. lean 37,187 ± 4,239 nmol/24 h, P = 0.912). Acipimox significantly reduced ACTH secretion in the obese subjects (acipimox 5,850 ± 769 ng/24 h, P = 0.039 vs. placebo), whereas cortisol release did not change (acipimox 33,542 ± 3,436 nmol/24 h, P = 0.484 vs. placebo). In conclusion, spontaneous ACTH secretion is enhanced in obese premenopausal women, whereas cortisol production is normal. Reduction of circulating FFA concentrations by acipimox blunts ACTH release in obese women, which suggests that FFAs are involved in the pathophysiology of this neuroendocrine anomaly.

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