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From the Clinical Research Centers |
Nemours Children’s Clinic, Jacksonville, Florida 32207; Divisions of Endocrinology (N.M., V.H., S.W., A.R.), Physical Therapy (K.H.), and Pediatric Surgery (M.D.), Department of Medicine (J.D.V.), University of Virginia Medical Center, Charlottesville, Virginia 22908; and the Department of Medicine (R.J.U.), University of Texas Medical Branch, Galveston, Texas 77555-1060
Address all correspondence and requests for reprints to: Nelly Mauras, M.D., Nemours Children’s Clinic, 807 Nira Street, Jacksonville, Florida 32207. E-mail: nmauras{at}nemours.org
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Abstract |
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In conclusion, testosterone deficiency in young men is associated with a marked decrease in measures of whole body protein anabolism, decreased strength, decreased fat oxidation, and increased adiposity. These effects of testosterone deficiency are independent of changes in peripheral GH production and IGF-I concentrations, even though im IGF-I mRNA concentrations decrease. These data suggest a direct effect of androgens on whole body lipid and protein metabolism.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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These studies were approved by the Nemours Children’s Clinic clinical research review committee and the Baptist Medical Center institutional review committee. Six healthy young males (mean ± SEM age, 23.2 ± 0.5 yr) participated in these studies after informed written consent was obtained. They were all within 5% of their ideal body weight (Metropolitan Life Insurance Tables).
Study design
For 3 days before admission to our Clinical Research Center, each subject consumed a weight maintenance diet consisting of approximately 34 Cal/kg and 1.7 g/kg protein/day. Subjects were instructed to keep the same pattern of weekly exercise during these studies.
The afternoon before the isotope tracer studies, subjects underwent body composition analysis using skinfold thickness measurements and dual emission x-ray absorptiometry (DEXA; Hologic 2000, Waltham, MA). Isokinetic dynamometry of the left knee extensors and flexors was performed using a Biodex Dynamometer (Biodex Corp., Shirley, NY). After a 10-min training session, followed by 30 min of rest, maximum torque production and work measures were recorded for isometric and isokinetic tests. Isometric tests, with the knee placed at 45° of flexion, were performed with five contractions for 5 s each, with 10 s of rest between contractions. Isokinetic tests were performed for knee extension and flexion at 60°/s for 5 repetitions and at 180°/s for 21 repetitions.
On the morning of the first study (D1), after an overnight 14-h fast,
two iv heparin locks were placed, one in the antecubital vein for the
infusion of isotopes and another in a contralateral hand vein kept
heated for arterialized blood sampling (11). At 0800 h (time
zero), a primed, dose constant infusion of
L-[1-13C]leucine was started and was
continued uninterrupted for the next 240 min (
4.5 µmol/kg; 0.07
µmol/kg·min). Multiple blood, breath, and urine samples were
obtained at frequent intervals, as detailed below. Indirect calorimetry
was performed three times during the study using a CPX-MAX calorimeter
(Medical Graphics, St. Paul, MN).
Subjects were fed lunch at 300 min and were free to move around. A percutaneous muscle biopsy of the anterior quadriceps was performed under local anesthesia for the measurement of messenger ribonucleic acid (mRNA) gene expression of different proteins in muscle.
After the baseline study was completed, subjects began treatment approximately 1 week later with a long acting GnRH analog (GnRHa; Lupron, TAP Pharmaceuticals, Deerfield, IL), at a dose of 7.5 mg, im. Three weeks after the first injection, another injection was given, and the study was repeated identically 7 weeks later (D2).
Blood, urine, and breath samples
During the isotope infusions, blood was withdrawn at -5, 30,
90, 150, 180, 210, and 240 min in both studies for determination of the
isotopic enrichments of 
-ketoisocaproic acid (KIC). At 0, 120, and
240 min, blood samples were collected for the measurement of serum
total and free testosterone, insulin, and glucose and plasma IGF-I and
IGF-binding protein-3 (IGFBP-3) concentrations. Amino acid
concentrations were also measured in the plasma samples. Serum samples
were obtained at 10-min intervals for 6 h during these studies,
from -60 min through 300 min for the assessment of GH concentration
profiles. Expired air samples were obtained at -10, 0, 160, 180, 200,
and 220 min on each study day to measure the expired labeled
13CO2. A 4-h urine collection for measurement
of urea nitrogen excretion was obtained during the 4-h isotope tracer
infusions.
Isotopes
L-[1-13C]Leucine (99% enriched; Cambridge Isotopes, Andover, MA) was determined to be sterile and pyrogen free and was prepared using 0.9% nonbacteriostatic saline.
Assays
Plasma enrichments of [1-13C]KIC were determined at the Nemours Children’s Clinic Core Endocrine/Metabolic Laboratory by gas chromatography-mass spectrometry as previously described (12). 13CO2 enrichments were determined using a dual inlet isotope ratio mass spectrometer (13, 14). The intraassay coefficient of variation (CV) for the isotopic enrichments of [13C]KIC was 1.1%, and that for 13CO2 was 0.22%. Plasma amino acid concentrations were measured by an ion exchange method using a Beckman 6300 Amino Acid Analyzer (Beckman Instruments, Fullerton, CA) with an intraassay CV of 2.5%. Total serum testosterone was measured by RIA using kits from Diagnostic Products Corp. (Los Angeles, CA), and free testosterone was measured by radioimmunometric assay using a kit from Diagnostic Systems Laboratories (Houston, TX) at the Mayo Clinic General Clinical Research Center (GCRC) Core Laboratory (Rochester, MN), with intraassay CVs of 13.6% and 11%, respectively. IGF-I and IGFBP-3 concentrations were measured by radioimmunometric assays with intraassay CVs of 6% and 5%, respectively. Insulin was measured by a chemiluminescence assay with a CV of 5%. GH was measured by a highly sensitive chemiluminescence assay at the University of Virginia GCRC Core Laboratory with an intraassay CV of 4.6%. Glucose was measured by a glucose oxidase method using a Beckman Glucose Analyzer (Beckman Instruments). Urinary nitrogen excretion was measured using a Kodak Ektachem urease method (Rochester, NY). Substrate oxidation and energy expenditure rates were measured by indirect calorimetry using a mouthpiece with a CPX-MAX Calorimeter (Medical Graphics Corp.).
Ribonuclease protection assays
Percutaneous muscle biopsy samples were placed in liquid
nitrogen and kept frozen at -70 C until assayed. Total RNA was
isolated from the samples using RNAzol B (Tel-Test, Friendswood, TX).
The ribonuclease protection assay was performed as described previously
(3, 15), using human complementary DNA (cDNA) clones for IGF-I,
IGFBP-4, actin, and myosin. The IGF-I and IGFBP-4 clones have been
described previously (3). The myosin cDNA clone contains the myosin
light chains MLC1 and MLC3 from fast skeletal
muscle fibers (16, 17). These were cloned from human fetal tissue and
are the products of alternative splicing of one gene (17). They are the
major isoforms of adult skeletal muscle (17). The -actin cDNA clone
is a full-length clone described by Gunning et al. (18). The
amount of total RNA used for each assay is as follows: IGF-I, 15 µg;
IGFBP-4, 10 µg; and actin and myosin, 2 µg. The RNA-protected bands
were detected with a 425E Phosphor Imager (Molecular Dynamics,
Sunnyvale, CA), and band intensities measured with the ImageQuant
analysis program. All bands were corrected for loading differences by
simultaneously measuring band densities of the housekeeping gene, human
glyceraldehyde 3-phosphate dehydrogenase (G3PD; Ambion, Austin,
TX).
Calculations
Leucine kinetics. Isotope dilution methods using the essential amino acid leucine were used in these experiments. This model assumes that at steady state in the post absorptive state the rate of appearance (Ra) of the tracer equals its disappearance (Rd), and hence, Rd can be partitioned into oxidative and nonoxidative losses or nonoxidative leucine disposal (NOLD). The latter serves as an index of whole body protein synthesis. Plasma enrichments of [1-13C]KIC were used as the index of intracellular enrichment of leucine in the reciprocal pool model (19, 20). All estimates were made at near steady state, between 160-240 min of infusion. The Ra of leucine, leucine oxidation rates, and NOLD were calculated as previously described (20).
Substrate oxidation rates. These combustion equations calculate the oxidation of substrates (sugars, lipids, and proteins) from the rates of O2 and CO2 exchanged and total nitrogen excretion in the urine as previously described (21).
Deconvolution. The GH concentration series was analyzed using deconvolution mathematical modeling, and the amplitude, the frequency of GH bursts, as well as the GH production rates were measured as previously described (22).
Body composition. DEXA scan data were used to estimate body composition changes. Fat-free mass (FFM) represents the sum of nonfat mass plus bone mineral content, as calculated using the tissue composition reference bar of Hologic.
Statistics. Each subject served as his own control; hence, paired Student’s t tests were used to compare differences after treatment. Significance was established at P < 0.05.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Table 1
shows the changes in total
and free testosterone concentrations in these subjects during the 10
weeks of the experiments. Both were markedly suppressed, similar to
levels found in prepuberty or very early puberty. There was a marked
correlation between the body composition measurements made by skinfold
thickness vs DEXA (FFM: r2 = 0.9; P =
1.0 x 10-9; fat mass: r2 = 0.83;
P = 4.5 x 10-8); hence, only data
generated by DEXA are reported. There were no significant changes in
total body weight or BMI during these experiments; however, there was a
significant decrease in FFM (P = 0.005) and a
concomitant increase in percent fat mass during hypogonadism
(P = 0.001).
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There was a remarkable decrease in the Ra of leucine, a measure of
whole body proteolysis, after hypogonadism, which was accompanied by a
parallel decrease in the measure of whole body protein synthesis (Fig. 1). These differences were comparable
whether the data were expressed as total kilograms or kilograms of FFM.
There were no significant changes in plasma amino acid concentrations
after treatment (Table 2).
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Table 3 summarizes results of the
changes in the rates of carbohydrate, protein, and lipid oxidation as
measured by indirect calorimetry. There were no significant changes in
carbohydrate and protein oxidation rates, but there was a clear trend
toward lower lipid oxidation rates after 10 weeks of hypogonadism
(-31%; P = 0.05); hence, the resting energy
expenditure was also lower after treatment (-9%; P =
0.05).
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Isokinetic dynamometry of the knee extensors showed lower strength
at 60° and 180°/s after 10 weeks of hypogonadism [at 60°/s: D1,
186 ± 15 Newton meters; D2, 175 ± 13; P =
0.01; at 180°/s: D1, 146 ± 11; D2, 135 ± 8;
P = 0.07; (by one-tailed test, P =
0.035); Fig. 2]. The isometric testing
results were: D1, 166 ± 13 Newton meters ; D2, 158 ± 13
(P = 0.21); the isokinetic testing results of the
flexors were: D1, 104 ± 13; D2, 95 ± 8 (P =
0.17) at 60°; and D1, 85 ± 8; D2, 76 ± 3
(P = 0.13) at 180°.
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Deconvolution analysis of the GH concentration series performed by
frequent blood sampling (every 10 min) for 6 h revealed no
decreases in the mean or peak GH concentrations in these young men
during the hypogonadal state or in the GH production rates (Table 4). Actually, basal GH secretion was
increased after induction of hypogonadism. Comparably, the circulating
IGF-I concentrations did not change significantly despite 10 weeks of
hypogonadism, with an actual trend toward higher concentrations on D2
(P = 0.08). IGFBP-3 concentrations increased during
treatment (P < 0.05). Insulin concentrations showed no
significant increase during treatment, whereas circulating glucose
concentrations remained normal (Table 5).
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IGF-I mRNA concentrations were significantly decreased after 10
weeks of hypogonadism (D1, 5.4 ± 0.4; D2, 3.7 ± 0.4;
P = 0.04; Fig. 3).
Concentrations of the inhibitory IGFBP-4 tended to be increased, but
did not reach significance (D1, 1.1 ± 0.2; D2, 1.7 ± 0.4;
P = 0.2). Actin and myosin mRNA concentrations did not
change with hypogonadism (actin: D1, 1.7 ± 0.3; D2, 2.0 ±
0.5; P = 0.5; myosin: D1, 1.4 ± 0.5; D2, 1.1
± 0.3; P = 0.5).
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Discussion |
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These changes in body composition are congruent with the well
established observations of increased adiposity and decreased lean body
mass of both hypogonadal and elderly men reported previously (3, 4, 5).
Bhasin et al. showed significant anabolic changes in body
composition and strength in hypogonadal men treated for 10 weeks with
testosterone, but no changes in the whole body protein
turnover/synthesis rates (5). These differences can be readily
accounted for by the acuteness and severity of the androgen deficiency
observed in the present studies, as testosterone concentrations
decreased from the mid-500 ng/dL range to the prepubertal to early
pubertal range (30 ng/dL). The changes reported here, however, are
opposite; they mirror those observed by us in prepubertal boys treated
with testosterone (2) and confirm our previous findings that
testosterone increases both the rates of whole body proteolysis (as
measured by the leucine Ra) and protein synthesis (NOLD) with a net
anabolic effect. These changes in the rates of whole body kinetics were
not due to depletion of the plasma amino acid pool, as the
concentrations of all amino acids after 10 weeks of hypogonadism were
comparable to baseline levels. As the availability of amino acids from
endogenous sources declined, despite the maintenance of oxidative
rates, there was a net decrease in protein synthesis and, overall, less
anabolism after treatment. These changes in whole body kinetics were
accompanied by marked reductions in quadriceps muscle strength, as
measured by isokinetic dynamometry of the knee extensors at 60° and
180°. The isometric test did not show any detectable changes during
these studies; the latter we believe to be due to the inability of
these subjects to give a consistent maximum effort during the test.
The induction of hypogonadism in these young men was not accompanied by any decrease in systemic GH or IGF-I production in any of the subjects studied, as measured by deconvolution analysis of the pulsatile GH concentration series using a highly sensitive assay. Neither mean and peak GH and IGF-I concentrations nor GH production rates were decreased by the severe decrease in testosterone concentrations. The basal GH secretory rate increased after 10 weeks of hypogonadism, suggestive of changes in GH-binding protein levels or GH distribution volume. We do not believe that the lack of change in GH production (with an actual increase in basal secretion) was affected by the lack of nighttime sampling. First, the differences in day/night pulsatility are particularly pronounced in puberty, and our subjects are young adult, postpubertal males. Second, the studies were performed during a 14- to 18-h fast, which typically enhances GH production and overall pulsatility (23). Third, the studies are paired, making comparisons by far more robust. The severe metabolic changes observed here appear to be directly related to androgen deficiency and not due to GH/IGF-I deficiency. Additionally, the IGFBP-3 concentrations were mildly, but significantly, increased during treatment with GnRHa. As IGFBP3 is a GH-dependent protein, it is possible that the bioactivity of GH may be increased and/or the small basal GH secretion rates may have influenced binding protein levels on D2, resulting in an increase in IGFBP-3. As IGFBP-3 may potentiate the effects of IGF-I in vivo (24), the rise in IGFBP-3 may represent a compensatory phenomena to maintain a basic anabolic rate in severe androgen deficiency.
There were, however, significant decreases in im mRNA concentrations for IGF-I and a trend toward increased IGFBP-4 gene expression, the main inhibitory binding protein for IGF-I in muscle (25). The gene expression for actin and myosin in muscle was not altered by the systemic decrease in testosterone concentrations. These observations are congruent with the observation made in elderly men treated with testosterone (3) and suggest that, within skeletal muscle tissue, androgens are necessary for local IGF-I production, independent of GH production and systemic IGF-I concentrations. IGF-I and its type I receptor are ubiquitously expressed in skeletal muscle and appear to be important in both the proliferation and differentiation of skeletal myocytes (26). Even though the gene expression of actin and myosin, the main contractile proteins of skeletal muscle, were not altered during severe hypogonadism, testosterone deficiency was associated with a marked decrease in measures of muscle strength, indicating that other mechanisms besides changes in muscle protein expression are affected by this severe degree of androgen deficiency. Data reported to date do not show an effect of the GH/IGF-I system to enhance muscle strength (27), whereas testosterone administration to normal men has been shown to increase FFM and muscle size in normal men (28). In addition, the decrease in systemic, noncontractile protein synthesis and increased adiposity may also play a role in the decrease in strength observed here.
Young men treated with a GnRHa were less efficient in their oxidation of fat, with a consequent decrease in the resting energy expenditure, which probably explains the increase in adiposity and the decrease in lean body mass observed during these experiments. The mechanisms for these findings are not completely understood; however, several considerations apply. First, concentrations of GH, a significant lipolytic hormone, did not decrease during these experiments. Insulin concentrations, on the other hand, did not increase significantly after hypogonadism. Plasma catecholamines were not measured in this paradigm; however, the studies were paired identically in each subject; hence, it is unlikely that the level of stress, and hence catecholamine production, would have been altered. Androgenic hormones, on the other hand, have been shown to stimulate lipolysis in a variety of species and experimental designs. Testosterone treatment of rat adipose precursor cells causes an increase in the number of ß-adrenergic receptors as well as externalization of those receptors, and increases the forskolin-induced (cAMP-mediated) lipolysis (29, 30). In addition, testosterone increases triacylglycerol lipase activity (31). When given to hypophysectomized rats, testosterone does not affect lipolysis, but when given in conjunction with GH, it normalizes lipolysis to a greater extent than GH alone, demonstrating that GH and testosterone have additive effects on lipolysis (32). Even though lipolysis was not directly measured in the present experiments, the observed decreases in lipid oxidation rates and significant increases in overall adiposity, despite the presence of normal GH production, are strongly suggestive that testosterone per se has significant effects on the regulation of fat metabolism.
In summary, severe androgen deficiency in young men was associated with decreased lean body mass and increased adiposity, decreased lipid oxidation and energy expenditure rates, decreased rates of whole body protein synthesis, and decreased leg muscle strength. These findings were not associated with changes in circulating amino acid concentrations. These changes were associated with decreased gene expression for IGF-I in muscle, but no peripheral decreases in GH and IGF-I production. We conclude that androgens can directly affect systemic protein synthesis, independent of the effect of peripheral GH and IGF-I. The latter may be important when an anabolic effect is the desired effect in the treatment of both elderly and young men.
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Acknowledgments |
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Footnotes |
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Received November 14, 1997.
Revised February 12, 1998.
Revised March 4, 1998.
Accepted March 11, 1998.
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References |
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-, ß-, and 
-actin mRNAs: skeletal but not cytoplasmic
actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 3:787-795.This article has been cited by other articles:
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I. Sinha-Hikim, W. E. Taylor, N. F. Gonzalez-Cadavid, W. Zheng, and S. Bhasin Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5245 - 5255. [Abstract] [Full Text] [PDF]
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 N. A. Evans Current Concepts in Anabolic-Androgenic Steroids Am. J. Sports Med., March 1, 2004; 32(2): 534 - 542. [Abstract] [Full Text] [PDF]
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L. J. Woodhouse, N. Gupta, M. Bhasin, A. B. Singh, R. Ross, J. Phillips, and S. Bhasin Dose-Dependent Effects of Testosterone on Regional Adipose Tissue Distribution in Healthy Young Men J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 718 - 726. [Abstract] [Full Text] [PDF]
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 S. Bhasin, W. E. Taylor, R. Singh, J. Artaza, I. Sinha-Hikim, R. Jasuja, H. Choi, and N. F. Gonzalez-Cadavid The Mechanisms of Androgen Effects on Body Composition: Mesenchymal Pluripotent Cell as the Target of Androgen Action J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2003; 58(12): M1103 - 1110. [Abstract] [Full Text] [PDF]
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P. Szulc, B. Claustrat, F. Marchand, and P. D. Delmas Increased Risk of Falls and Increased Bone Resorption in Elderly Men with Partial Androgen Deficiency: The MINOS Study J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5240 - 5247. [Abstract] [Full Text] [PDF]
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S. Bhasin Testosterone Supplementation for Aging-Associated Sarcopenia J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2003; 58(11): M1002 - 1008. [Abstract] [Full Text] [PDF]
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I. Sinha-Hikim, S. M. Roth, M. I. Lee, and S. Bhasin Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E197 - E205. [Abstract] [Full Text] [PDF]
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S. Bhasin and K. Herbst Testosterone and Atherosclerosis Progression in Men Diabetes Care, June 1, 2003; 26(6): 1929 - 1931. [Full Text] [PDF]
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 M. Nahrendorf, S. Frantz, K. Hu, C. von zur Muhlen, M. Tomaszewski, H. Scheuermann, R. Kaiser, V. Jazbutyte, S. Beer, W. Bauer, et al. Effect of testosterone on post-myocardial infarction remodeling and function Cardiovasc Res, February 1, 2003; 57(2): 370 - 378. [Abstract] [Full Text] [PDF]
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B. L. Herrmann, B. Saller, O. E. Janssen, P. Gocke, A. Bockisch, H. Sperling, K. Mann, and M. Broecker Impact of Estrogen Replacement Therapy in a Male with Congenital Aromatase Deficiency Caused by a Novel Mutation in the CYP19 Gene J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5476 - 5484. [Abstract] [Full Text] [PDF]
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G. Kilciler, M. Ozata, C. Oktenli, S.Y. Sanisoglu, E. Bolu, N. Bingol, M. Kilciler, I. C. Ozdemir, and M. Kutlu Diurnal Leptin Secretion Is Intact in Male Hypogonadotropic Hypogonadism and Is Not Influenced by Exogenous Gonadotropins J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5023 - 5029. [Abstract] [Full Text] [PDF]
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T. A. Roy, M. R. Blackman, S. M. Harman, J. D. Tobin, M. Schrager, and E. J. Metter Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E284 - E294. [Abstract] [Full Text] [PDF]
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I. Sinha-Hikim, J. Artaza, L. Woodhouse, N. Gonzalez-Cadavid, A. B. Singh, M. I. Lee, T. W. Storer, R. Casaburi, R. Shen, and S. Bhasin Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E154 - E164. [Abstract] [Full Text] [PDF]
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C. P. Lambert, D. H. Sullivan, S. A. Freeling, D. M. Lindquist, and W. J. Evans Effects of Testosterone Replacement and/or Resistance Exercise on the Composition of Megestrol Acetate Stimulated Weight Gain in Elderly Men: A Randomized Controlled Trial J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2100 - 2106. [Abstract] [Full Text] [PDF]
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M. R. Smith, J. S. Finkelstein, F. J. McGovern, A. L. Zietman, M. A. Fallon, D. A. Schoenfeld, and P. W. Kantoff Changes in Body Composition during Androgen Deprivation Therapy for Prostate Cancer J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 599 - 603. [Abstract] [Full Text] [PDF]
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A. Gentili, T. Mulligan, M. Godschalk, J. Clore, J. Patrie, A. Iranmanesh, and J. D. Veldhuis Unequal Impact of Short-Term Testosterone Repletion on the Somatotropic Axis of Young and Older Men J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 825 - 834. [Abstract] [Full Text] [PDF]
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A. M. Matsumoto Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2002; 57(2): M76 - 99. [Full Text]
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A. B. Singh, S. Hsia, P. Alaupovic, I. Sinha-Hikim, L. Woodhouse, T. A. Buchanan, R. Shen, R. Bross, N. Berman, and S. Bhasin The Effects of Varying Doses of T on Insulin Sensitivity, Plasma Lipids, Apolipoproteins, and C-Reactive Protein in Healthy Young Men J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 136 - 143. [Abstract] [Full Text] [PDF]
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 C. M. Kuhn Anabolic Steroids Recent Prog. Horm. Res., January 1, 2002; 57(1): 411 - 434. [Abstract] [Full Text] [PDF]
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S. Bhasin, L. Woodhouse, R. Casaburi, A. B. Singh, D. Bhasin, N. Berman, X. Chen, K. E. Yarasheski, L. Magliano, C. Dzekov, et al. Testosterone dose-response relationships in healthy young men Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1172 - E1181. [Abstract] [Full Text] [PDF]
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S. Basaria, J. T. Wahlstrom, and A. S. Dobs Anabolic-Androgenic Steroid Therapy in the Treatment of Chronic Diseases J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5108 - 5117. [Abstract] [Full Text] [PDF]
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R. J. Saad, B. S. Keenan, K. Danadian, V. D. Lewy, and S. A. Arslanian Dihydrotestosterone Treatment in Adolescents with Delayed Puberty: Does it Explain Insulin Resistance of Puberty? J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4881 - 4886. [Abstract] [Full Text] [PDF]
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P. J. Snyder Effects of Age on Testicular Function and Consequences of Testosterone Treatment J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2369 - 2372. [Full Text] [PDF]
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V. Y. Hayes, R. J. Urban, J. Jiang, T. J. Marcell, K. Helgeson, and N. Mauras Recombinant Human Growth Hormone and Recombinant Human Insulin-Like Growth Factor I Diminish the Catabolic Effects of Hypogonadism in Man: Metabolic and Molecular Effects J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2211 - 2219. [Abstract] [Full Text]
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M. M. Bamman, J. R. Shipp, J. Jiang, B. A. Gower, G. R. Hunter, A. Goodman, C. L. McLafferty Jr., and R. J. Urban Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans Am J Physiol Endocrinol Metab, March 1, 2001; 280(3): E383 - E390. [Abstract] [Full Text] [PDF]
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S. M. Harman, E. J. Metter, J. D. Tobin, J. Pearson, and M. R. Blackman Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 724 - 731. [Abstract] [Full Text]
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B. A. Gower and L. Nyman Associations among Oral Estrogen Use, Free Testosterone Concentration, and Lean Body Mass among Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4476 - 4480. [Abstract] [Full Text]
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N. Mauras, V. Martinez, A. Rini, and J. Guevara-Aguirre Recombinant Human Insulin-Like Growth Factor I Has Significant Anabolic Effects in Adults with Growth Hormone Receptor Deficiency: Studies on Protein, Glucose, and Lipid Metabolism J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3036 - 3042. [Abstract] [Full Text]
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P. J. Snyder, H. Peachey, J. A. Berlin, P. Hannoush, G. Haddad, A. Dlewati, J. Santanna, L. Loh, D. A. Lenrow, J. H. Holmes, et al. Effects of Testosterone Replacement in Hypogonadal Men J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2670 - 2677. [Abstract] [Full Text]
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N. Mauras, K. O. O’Brien, K. O. Klein, and V. Hayes Estrogen Suppression in Males: Metabolic Effects J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2370 - 2377. [Abstract] [Full Text]
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N. Mauras, K. O. O’Brien, S. Welch, A. Rini, K. Helgeson, N. E. Vieira, and A. L. Yergey Insulin-Like Growth Factor I and Growth Hormone (GH) Treatment in GH-Deficient Humans: Differential Effects on Protein, Glucose, Lipid, and Calcium Metabolism J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1686 - 1694. [Abstract] [Full Text]
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Is Obesity an Outcome of Gonadotropin-Releasing Hormone Agonist Administration? Analysis of Growth and Body Composition in 110 Patients with Central Precocious Puberty J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4480 - 4488. [Abstract] [Full Text]
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P. J. Snyder, H. Peachey, P. Hannoush, J. A. Berlin, L. Loh, D. A. Lenrow, J. H. Holmes, A. Dlewati, J. Santanna, C. J. Rosen, et al. Effect of Testosterone Treatment on Body Composition and Muscle Strength in Men Over 65 Years of Age J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2647 - 2653. [Abstract] [Full Text]
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M. Sheffield-Moore, R. J. Urban, S. E. Wolf, J. Jiang, D. H. Catlin, D. N. Herndon, R. R. Wolfe, and A. A. Ferrando Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2705 - 2711. [Abstract] [Full Text]
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A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human Endocr. Rev., December 1, 1998; 19(6): 717 - 797. [Abstract] [Full Text]
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M. I. Lewis, G. D. Horvitz, D. R. Clemmons, and M. Fournier Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E483 - E490. [Abstract] [Full Text] [PDF]
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A. A. Ferrando, M. Sheffield-Moore, C. W. Yeckel, C. Gilkison, J. Jiang, A. Achacosa, S. A. Lieberman, K. Tipton, R. R. Wolfe, and R. J. Urban Testosterone administration to older men improves muscle function: molecular and physiological mechanisms Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E601 - E607. [Abstract] [Full Text] [PDF]
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