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J. F. Tait
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S. A. S. Tait
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ABSTRACT

Earlier views indicated that globulin (corticosteroid-binding globulin (CBG) or sex hormone-binding globulin (SBG)) but not albumin binding in plasma, protects steroids from splanchnic metabolism in man. Also, the splanchnic extraction (HE) of a steroid seemed to be highly dependent on the rate of disassociation of the steroid–protein complex. However, the faster rate of disassociation (τ½ = 0·9 s) of cortisol–CBG, as determined by later accurate fluorescence methods, intuitively meant that this complex must disassociate completely in a single 9 s passage through the liver. The low HE of total cortisol was then a puzzling anomaly.

Using a differential equation solver (TUTSIM) and a model with unbound, albumin- and globulin-bound pools of steroid (with metabolism of unbound and also possibly albumin-bound steroid), the mechanism of splanchnic metabolism has been studied. The 'complex', probably most realistic, model includes 13 steroids, which can simultaneously bind to plasma albumin, CBG and SBG. The steroid concentration and numbers of occupied binding sites of the globulins decrease during the time of metabolism. The experimental data used are the in-vitro binding characteristics of the steroid–protein complexes, including the equilibrium constants and rates of disassociation and the in-vivo HE of nine steroids, usually measured by direct analysis of hepatic venous blood. However, the HE of cortisol had to be calculated from the metabolic clearance rate/splanchnic blood flow, giving a maximum value of 12%.

The fractional metabolic rate of unbound steroid is generally represented by e. A certain value of e (RE) is required to give a remaining steroid concentration after 9 s of metabolism, which is made equal to (1–HE) in the model to simulate splanchnic extraction. If the fractional rate of metabolism of albumin-bound steroid is h (f = h/e), then RE will depend on the value of f. The maximum RE for cortisol is RE0 = 0·42 and RE1 = 0·16 for f = 0 and 1 respectively. For either value of RE, there will be the appreciable reassociation of cortisol to CBG after disassociation of the cortisol–CBG complex. With such reassociation, the total cortisol remaining after 9 s metabolism is fairly independent of the rate of disassociation of the cortisol–CBG complex. This explains the low total HE of cortisol in spite of the high rate of disassociation of cortisol–CBG. Generally, for all nine steroids studied, HE estimations in vivo in humans indicate that the steroid–globulin disassociation rate will only be markedly rate-limiting for dihydrotestosterone–SBG and, to a lesser extent, testosterone–SBG. These results are examples of the principle that the divergence in hormone concentration with the disassociation rate of the hormone-protein complex after metabolism depends on the value of e.

The RE0 and RE1 values of the nine steroids: aldosterone, progesterone, testosterone, dihydrotestosterone, androstenedione, androstanediol, oestradiol, oestrone and cortisol have also been calculated from all in-vivo HE estimates. If it is assumed that the steroid in the albumin-bound pool is not metabolized (f = 0), then the RE0 values of the nine steroids considered have a large variation (s.d./mean = 115%). There is a correlation between the RE0 values and their albumin-binding index (BIA). However, if f = 1 then the variation of RE is smaller (s.d./mean = 36%) and there is no correlation between RE1 and BIA. The ratio of the RE0 and RE1 values for a particular steroid is nearly equal to (1 + BIA), which is determined solely by the dynamics of the situation. However, the appropriate value of f depends on the mechanisms involved.

With the F1 hypothesis (f = 1), albumin binding does not protect steroids from splanchnic extraction because of metabolism of albumin-bound steroid. With the FO hypothesis (f = 0), this seeming lack of protection of albumin binding is essentially artefactual. Albumin-bound steroid would not be metabolized directly but the fractional rate of metabolism of unbound steroid would be increased with the decreasing polarity of the steroid (i.e. with increasing BIA). With the available data, the choice between the hypotheses can only be on an intuitive basis.

Journal of Endocrinology (1991) 131, 339–357

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Research Article
DOI:
https://doi.org/10.1677/joe.0.1310339
Volume/Issue:
Volume 131: Issue 3
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Cheryl A Conover Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, 200 First Street SW, 5-194 Joseph, Rochester, Minnesota 55905, USA

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Megan A Mason Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, 200 First Street SW, 5-194 Joseph, Rochester, Minnesota 55905, USA

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James A Levine Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, 200 First Street SW, 5-194 Joseph, Rochester, Minnesota 55905, USA

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Colleen M Novak Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, 200 First Street SW, 5-194 Joseph, Rochester, Minnesota 55905, USA

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posits that a decrease in overall metabolic rate decreases the production of reactive oxygen species (ROS) during respiration, thereby slowing the aging process (reviewed in Masoro 2005 ). If so, then reduced IGF signaling might result in decreases in

Article Type:
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DOI:
https://doi.org/10.1677/JOE-08-0179
Volume/Issue:
Volume 198: Issue 3
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Sean A Newsom Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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Jennifer C Richards Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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Tyler K Johnson Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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Jessica N Kuzma Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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Mark C Lonac Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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Roger J Paxton Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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Grant M Rynn Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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Wyatt F Voyles Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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Christopher Bell Department of Health and Exercise Science, Colorado State University, 205E Moby B-Complex, Fort Collins, Colorado 80523-1582, USA

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overwhelming: during β-AR blockade, both resting metabolic rate (RMR) and the magnitude of increase in EE following energy intake (thermic effect of feeding) are decreased ( Tappy et al . 1986 , Welle et al . 1991 , Bell et al . 2001 , Monroe et al

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DOI:
https://doi.org/10.1677/JOE-10-0152
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Volume 206: Issue 3
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Marian Ludgate School of Medicine, Centre for Endocrine and Diabetes Sciences, Cardiff University, Heath Park, Cardiff CF14 4XN, UK

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all of the required components and are able to produce thyroid hormone ( Meischl et al . 2008 ). Thyroid hormones are essential to the development and maintenance of, for example, the brain and skeletal system and for regulation of the basal metabolic

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https://doi.org/10.1530/JOE-11-0159
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Volume 210: Issue 1
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Rosalba Senese
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Federica Cioffi Dipartimento di Scienze e Tecnologie Ambientali, Dipartimento di Scienze e Tecnologie, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Via Vivaldi 43, 81100 Caserta, Italy

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Pieter de Lange
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Fernando Goglia Dipartimento di Scienze e Tecnologie Ambientali, Dipartimento di Scienze e Tecnologie, Biologiche e Farmaceutiche, Seconda Università degli Studi di Napoli, Via Vivaldi 43, 81100 Caserta, Italy

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Antonia Lanni
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( Kunitake et al . 1989 ) and to increase metabolic rate in obese patients ( Dumas et al . 1982 ). It has been shown to be more potent than T 3 as both a β-adrenergic stimulator of uncoupling protein 1 and inducer of lipoprotein lipase mRNA, D3 activity

Article Type:
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DOI:
https://doi.org/10.1530/JOE-13-0573
Volume/Issue:
Volume 221: Issue 2
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Sujith Rajan Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Kripa Shankar Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Muheeb Beg Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Salil Varshney Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Abhishek Gupta Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Ankita Srivastava Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Durgesh Kumar Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Raj K Mishra SIPS Superspeciality Hospital, Lucknow, Uttar Pradesh, India

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Zakir Hussain Division of Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Jiaur R Gayen Division of Pharmacokinetics, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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Anil N Gaikwad Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India
Academy of Scientific and Innovative Research, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India

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animal monitoring system (CLAMS) Oxymax/CLAMS (Columbus Instruments, Columbus, OH, USA) were used to quantitate food intake, locomotor activity, oxygen consumption (VO 2 ), carbon dioxide production (VCO 2 ), metabolic rate, and heat production. Mice

Article Type:
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DOI:
https://doi.org/10.1530/JOE-16-0099
Volume/Issue:
Volume 230: Issue 3
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I Sadaf Farooqi MRC Metabolic Diseases Unit, Metabolic Research Laboratories, Wellcome Trust–MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

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Stephen O'Rahilly MRC Metabolic Diseases Unit, Metabolic Research Laboratories, Wellcome Trust–MRC Institute of Metabolic Science, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK

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unable to demonstrate a major acute effect of leptin administration on basal metabolic rate as measured by indirect calorimetry, total energy expenditure using chamber calorimetry, or free-living energy expenditure using the doubly-labelled water method

Article Type:
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DOI:
https://doi.org/10.1530/JOE-14-0480
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Volume 223: Issue 1
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Cássio M Villicev Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Fatima R S Freitas Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Marcelo S Aoki Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Cássio Taffarel Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Thomas S Scanlan Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Anselmo S Moriscot Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Miriam O Ribeiro Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Antonio C Bianco Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Cecília H A Gouveia Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof Lineu Prestes, 2415 Sao Paulo 05508-900, Brazil
School of Arts, Sciences & Humanities, University of Sao Paulo, Sao Paulo, Brazil
Department of Biosciences, Mackenzie Presbyterian University, Sao Paulo, Brazil
Departments of Pharmaceutical Chemistry & Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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result in some therapeutically desirable effects, such as increased metabolic rate, lipolysis, cholesterol lowering, improvement of heart contractility and thyroid-stimulating hormone (TSH) suppression, which is beneficial in patients with thyroid cancer

Article Type:
Research Article
DOI:
https://doi.org/10.1677/joe.1.07066
Volume/Issue:
Volume 193: Issue 1
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Xuan Zhou Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

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Yanan Zhang Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

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Youwen Yuan Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

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Fei Teng Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

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Jiayang Lin Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

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Xueru Ye Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

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Yaojin Pan Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

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Huijie Zhang Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China
Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, China

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Introduction Thyroid hormone (TH) performs vital functions in energy expenditure and homeostasis. Under physiological circumstances, TH is essential for sustaining basal metabolic rate (BMR), facilitating adaptive thermogenesis, and modulating

Article Type:
Research Article
DOI:
https://doi.org/10.1530/JOE-23-0412
Volume/Issue:
Volume 262: Issue 2
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Noelia Martínez-Sánchez Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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José M Moreno-Navarrete CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain

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Cristina Contreras Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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Eva Rial-Pensado Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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Johan Fernø Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
Department of Clinical Science, KG Jebsen Center for Diabetes Research, University of Bergen, Bergen, Norway

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Rubén Nogueiras Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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Carlos Diéguez Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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José-Manuel Fernández-Real CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
Department of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Institut D’investigació Biomèdica de Girona (IdIBGi) and University of Girona, Girona, Spain

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Miguel López Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, Spain
CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain

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the metabolic rate and the patients suffering from this condition undergo body weight loss, despite increased food intake; quite the opposite, hypothyroid patients show lowered metabolic rate and reduced food intake ( Brenta et al . 2007 , Kaptein

Article Type:
Research Article
DOI:
https://doi.org/10.1530/JOE-16-0425
Volume/Issue:
Volume 232: Issue 2
Open access