| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Reproductive Endocrinology |
Klinik II und Poliklinik für Innere Medizin, Universität zu Köln (F.J., D.M.-W., W.K.), 50924 Koln; Lilly Deutschland (W.F.B.), 61350 Bad Homburg; Universitätskinderklinik (W.F.B., P.E., W.R.), 35385 Giessen; and Abteilung für Endokrinologie, Zentrum für Innere Medizin, Universitätsklinik Essen (E.V., D.R.), 45122 Essen, Germany
Address all correspondence and requests for reprints to: Dr. Friedrich Jockenhövel, Klinik II und Poliklinik für Innere Medizin, Universität zu Köln, 50924 Köln, Germany.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Hypogonadal men with T levels of 3.6 nmol/L or less and off
substitution therapy for at least 3 months were assigned to two
treatment groups: testosterone enanthate (TE; 250 mg, im, every 21
days; n = 10) or a single sc implantation of 1200 mg crystalline T
(TPEL; n = 12). Blood samples for determination of T,
5
-dihydrotestosterone (DHT), sex hormone-binding globulin, and
17ß-estradiol were obtained before therapy and then every 21 days
until day 189 and at follow-up visits on days 246 and 300. Serum OB
levels were assessed on days 0, 42, 84, 126, 168, and 300. OB levels
were referred to a normal range for men based on the analysis of OB
levels in 393 adult men.
Substitution with T led to a large rise in T and DHT in both groups
compared to baseline values (average T, days 21–189: TE, 14.33 ±
2.63 nmol/L; TPEL, 24.98 ± 1.64; average DHT, days 21–189: TE,
4.20 ± 0.57 nmol/L; TPEL, 5.11 ± 0.56;
P 
0.05). Concomitantly, 17ß-estradiol
increased in both groups, and sex hormone-binding globulin levels were
significantly decreased. At baseline, serum OB levels in hypogonadal
men were 3-fold elevated compared to those in normal men (12.39 ±
2.93 µg/L vs. 4.28 ± 0.52; P <
0.01) and not different between groups (TE, 13.7 ± 5.6; TPEL,
11.3 ± 2.9 µg/L). This elevation was retained after adjustment
for body mass index in the normal control group [TE, 1.45 ± 0.51
SD score (P < 0.0001); TPEL, 0.98
± 0.35 SD score (P < 0.0008)].
During T substitution serum OB was completely normalized (trough
levels: TE, 4.6 ± 1.0 µg/L; TPEL, 4.3 ± 0.9 µg/L). In
multiple regression analysis, the androgen (T plus DHT)/estrogen ratio
was the only significant determinant of OB levels (r = -0.32;
P < 0.01). At baseline, OB levels did not
correlate with body mass index, but during substitution, the
correlation was considerably improved.
We conclude that hypogonadal men exhibit elevated OB levels that are normalized by substitution with T. The only determinant of OB levels was the androgen/estrogen ratio, indicating a major influence of sex steroids on OB production. The interaction of T and OB might be part of a hypothalamic-pituitary-gonadal-adipose tissue axis that is involved in body weight maintenance and reproductive function.
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Initial studies in humans show that serum OB levels are most closely correlated with the percentage of body fat (8, 9). Nevertheless, men have lower serum OB concentrations than women with similar body mass indexs (BMIs) (8, 9, 10, 11). As the factors responsible for these differences are unknown, we undertook the present work to shed light on the effect of testosterone (T) on OB levels in men by substituting T in hypogonadal men.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In this single center study 22 men with hypogonadism, as
confirmed by 2 determinations of serum T yielding serum concentrations
less than 3.6 nmol/L (normal, >10 nmol/L), were randomly assigned to T
enanthate (TE; Testoviron depot 250, Schering, Berlin, Germany) or T
pellets (TPEL), a single sc implantation of 6 testosterone pellets each
containing 200 mg crystalline T (Organon, Oss, The Netherlands; Table 1
) (12). Previous testosterone medication (TE or T
undecanoate) had been suspended at least 3 months before the study
began. On days 0, 21, 42, 63, 84, 105, 126, 147, 168, and 189, blood
samples were drawn, and TE injections were administered. Study
medication lasted until day 210, and follow-up visits were conducted on
days 246 and 300. Serum samples for OB analysis were available for days
0, 42, 84, 126, 168, and 300. BMI was assessed on days 0, 105, and 300.
All men gave written informed consent; the study was approved by the
ethics committee of the University of Essen and followed the guidelines
of the Declaration of Helsinki 1975.
|
Hormones were measured by commercially available immunoassays;
T, sex hormone-binding globulin (SHBG), and 17ß-estradiol
(E2) were determined by RIA (Diagnostic Products
Corp., Los Angeles, CA), and 5-dihydrotestosterone (DHT) was
determined by RIA after oxidative destruction of T (Amersham,
Braunschweig, Germany). Inter- and intraassay variations were below 8%
for all assays except DHT (17%) (12).
OB was measured by a specific RIA as previously described (13). Recombinant human OB (gift from Dr. Heiman, Eli Lilly Research Laboratories, Indianapolis, IN) was used for production of antiserum in rabbits and for preparation of tracer by the chloramine-T method (14) and of standards. The assay buffer was composed of 0.05 mol/L sodium phosphate (pH 7.4), 0.1 mol/L NaCl, 0.05% (wt/vol) NaN3, 0.1% (vol/vol) gelatin from teleost fish (Sigma, Munich, Germany), and 0.1% (vol/vol) Triton X-100. The assay volume was 0.3 mL. After incubation at room temperature overnight, bound and unbound tracers were separated using the second antibody technique (14). Maximal binding of tracer was 37–45%, and half-maximal binding occurred at 0.9 µg/L unlabeled OB. Excellent parallelism was obtained with serial dilutions of human serum, and spiking experiments with 0.1 ng/tube yielded a recovery of 97 ± 2.1%. The sensitivity was 0.03 µg/L, and the intra- and interassay variations were 0.8% and 8.5%, respectively.
With this assay system a normal reference range of serum OB levels was established based on the analysis of sera from 393 healthy men, which proved to be BMI, but not age, dependent. The best-fit regression line for the 50th percentile was an exponential curve: OB = 0.0237 x e(0.1985 x BMI). The corresponding equations for the 5th and 95th percentiles were: OB = 0.0237 x e(0.1985 x BMI - 1.0473) and OB = 0.0237 x e(0.1985 x BMI + 1.0473), respectively. To adjust for BMI, OB levels were converted to SD scores by the following equation: OB SD score = [ln (OB) - ln (0.0237) - (0.1985 x BMI)]/0.6386, taking the log normal distribution of serum OB levels into account.
Statistical analysis
Results are reported as the mean ± SE. The androgen/estrogen ratio (A/E ratio) was derived by dividing the total androgen concentration (T plus DHT; nanomoles per L) by the estrogen concentration (picomoles per L). The area under the hormone curve was calculated by the trapezoidal rule. Statistical comparisons use a paired t test or repeated measures ANOVA as appropriate, with the level of significance set at P < 0.05 (by Student-Newman-Keuls test) using the SPSS (SPSS, Chicago, IL) software package. Changes in BMI (kilograms of body weight divided by height in meters squared) were tested with the Wilcoxon matched pairs sign test. Pearson’s correlation analysis and multiple regression analysis were applied to assess the relation of hormone parameters and BMI to OB concentrations.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In both groups, serum T was normalized during substitution, with
average T levels of 14.33 ± 2.63 nmol/L (days 21–189) in the TE
group and 24.98 ± 1.64 nmol/L in the TPEL group (Fig. 1). Whereas implantation of T pellets produced large
increases in DHT and E2, this was less pronounced
in the TE group: DHT, days 21–189: TE, 4.20 ± 0.57 nmol/L; TPEL,
5.11 ± 0.56; E2, days 21–189: TE,
95.6 ± 7.3 pmol/L; TPEL, 102.1 ± 6.1; Fig. 1). Accordingly,
the A/E ratio was elevated in both groups, and serum sex
hormone-binding globulin levels decreased in response to T substitution
in both groups (Fig. 1). Due to the study design, with the final TE
injection on day 189, all changes were more prolonged in the TE
group.
|
At baseline, mean OB levels for all 22 hypogondal men were
12.39 ± 2.93 µg/L and significantly elevated (P
< 0.01) compared to the BMI-dependent normal range for men (+1.20
± 0.20 SD score). For normal men with similar BMI, a mean
OB level of 4.28 ± 0.52 µg/L (95th percentile, 12.19 ±
1.48 µg/L) was calculated (Fig. 2). In 7 of 22
hypogonadal men, OB levels exceeded the 95th percentile of the normal
range. Between treatment groups no significant differences in OB levels
were observed (TE, 13.70 ± 5.62; TPEL, 11.30 ± 2.87
µg/L).
|
). Serum OB concentrations
reached a nadir on day 126 with 4.61 ± 1.02 µg/L in the TE
group and 4.34 ± 0.91 µg/L in the TPEL group, not different
from their expected normal value. Parallel to the earlier decreases in
serum T and the A/E ratio in the TPEL group compared to the TE group,
OB levels started to increase in the TPEL group earlier than in the TE
group (Fig. 1). After cessation of substitution, OB levels completely
returned to the elevated baseline levels. There were now significant
differences in OB levels between men with primary and secondary
hypogonadism at any time point.
By single regression analysis, OB levels correlated significantly with
all hormone parameters (Table 2). However, in multiple
regression, the only factor significantly determining OB levels for
both groups was the A/E ratio (TE, r = -0.30 and
P = 0.034; TPEL, r = -0.34 and P
= 0.008).
|
0.05), but not in the TPEL group (day 0,
26.24 ± 0.80 kg/m2; day 105, 26.54 ± 0.67;
P = NS) and did return to baseline on day 300 (TE,
24.78 ± 0.83 kg/m2; TPEL, 26.69 ± 0.72). At baseline, serum OB levels (day 0) did not correlate with BMI on day 0 in either group (TE, r = -0.05 and P = 0.89; TPEL, r = 0.38 and P = 0.22) or when both groups were combined (r = 0.09; P = 0.76). Whereas the correlation was considerably improved in the TPEL group during and after substitution (OB on day 42 with BMI on day 105, r = 0.54 and P = 0.085; OB on day 300 with BMI on day 300, r = 0.60 and P = 0.04), in the TE group no significant correlation was observed.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The normalization of OB levels in hypogonadal men upon substitution of T indicates an important influence of sex steroids on the regulation of OB production. Due to its anabolic action, T increases lean body mass, but not adipose tissue, the source of OB (15, 16). Even extremely high doses of T do not change the percentage of body fat (15). Therefore, the 50% decline in serum OB levels observed during substitution of TE and TPEL cannot be accounted for by a possible decrease in the percent body fat. Thus, T substitution has lowered serum OB levels independently of its effects on the proportion of body fat, suggesting a regulatory role of T in OB production. The observation of similar pharmacodynamic effects on serum OB levels by the two T preparations with markedly different pharmacokinetics (12) is explained by the fact that the areas under the T vs. time curve might actually be quite similar for the two testosterone preparations when the initial supraphysiological levels of TE are considered. As blood was sampled only at the end of the injection interval, the serum T levels in the TE group are underestimated because they do not reveal the preceding high levels.
The mechanism by which T lowers OB production is unclear. Adipocytes specifically bind androgens (17) and appear to carry androgen receptors (18). Therefore, a direct suppressive effect of T on OB gene expression is possible. On the other hand, indirect effects of androgens on adipocyte metabolism have been shown. In vitro, T enhances the lipolytic activity and the activity of adenylate cyclase of adipocytes by increasing the number of ß-adrenergic receptors (17). The involvement of estrogens intracellularly derived from androgens is unlikely, because androgens and estrogens seem to have opposite effects on OB levels, and in vitro the effects of T on adipocytes are not influenced by aromatase inhibitors (17). Thus, T appears to directly cause the suppression of adipocyte OB production. The suppressive effect of T on OB might be the link between the frequent association of low serum T with visceral obesity (19, 20), which is an important risk factor for cardio-cerebrovascular disease and noninsulin-dependent diabetes mellitus (21, 22). The amount of intraabdominal fat mass is strongly negatively correlated with serum T levels (23), and T administration to men with visceral obesity is followed by an apparently region-specific decrease in abdominal adipose tissue (24). Possibly, hypogonadal men are in a state of OB resistance, which is corrected by the androgen-induced reduction of OB levels, thereby restoring responsiveness of the hypothalamus to OB action.
Impaired reproductive function due to hypothalamic dysfunction is a characteristic feature of all of the recessively transmitted obesities in rodents (25, 26, 27). Recent studies demonstrated that administration of recombinant OB during states of absent or low OB levels reverses or prevents the impairment of reproductive function (28, 29). Therefore, OB might be a modulator of reproductive function, signaling the central nervous system about the amount of fat tissue and thereby indicating reproductive adequacy, possibly by interaction with NPY (6). NPY has been shown to modulate GnRH release (30). In this case, sex steroids would be the natural corresponding part of the hypothalamic-pituitary-gonadal-adipose tissue axis, as is suggested by this study.
|
Acknowledgments |
|---|
Received March 12, 1997.
Revised April 16, 1997.
Accepted April 22, 1997.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  F. Laghi, N. Adiguzel, and M. J. Tobin Endocrinological derangements in COPD Eur. Respir. J., October 1, 2009; 34(4): 975 - 996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Kapoor, S Clarke, R Stanworth, K S Channer, and T H Jones The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes Eur. J. Endocrinol., May 1, 2007; 156(5): 595 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.L. Hendriks, J.C.F. Ket, P.G.A. Hompes, R. Homburg, and C.B. Lambalk Why does ovarian surgery in PCOS help? Insight into the endocrine implications of ovarian surgery for ovulation induction in polycystic ovary syndrome Hum. Reprod. Update, May 1, 2007; 13(3): 249 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. O. Hammoud, M. Gibson, C. M. Peterson, B. D. Hamilton, and D. T. Carrell Obesity and Male Reproductive Potential J Androl, September 1, 2006; 27(5): 619 - 626. [Full Text] [PDF]
|
|
|
|
 |
|
 J. L Downs and H. F Urbanski Aging-related sex-dependent loss of the circulating leptin 24-h rhythm in the rhesus monkey. J. Endocrinol., July 1, 2006; 190(1): 117 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Makinen, M. J. Jarvisalo, P. Pollanen, A. Perheentupa, K. Irjala, M. Koskenvuo, J. Makinen, I. Huhtaniemi, and O. T. Raitakari Increased Carotid Atherosclerosis in Andropausal Middle-Aged Men J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1603 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Laghi, A. Antonescu-Turcu, E. Collins, J. Segal, D. E. Tobin, A. Jubran, and M. J. Tobin Hypogonadism in Men with Chronic Obstructive Pulmonary Disease: Prevalence and Quality of Life Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 728 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schroth, J. Kratzsch, M. Groschl, M. Rauh, W. Rascher, and J. Dotsch Increased Soluble Leptin Receptor in Children with Nephrotic Syndrome J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5497 - 5501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Pagotto, A. Gambineri, C. Pelusi, S. Genghini, M. Cacciari, B. Otto, T. Castaneda, M. Tschop, and R. Pasquali Testosterone Replacement Therapy Restores Normal Ghrelin in Hypogonadal Men J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4139 - 4143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. Kratzsch, A. Lammert, A. Bottner, B. Seidel, G. Mueller, J. Thiery, J. Hebebrand, and W. Kiess Circulating Soluble Leptin Receptor and Free Leptin Index during Childhood, Puberty, and Adolescence J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4587 - 4594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Kraemer, H. Chu, and V. D. Castracane Leptin and Exercise Experimental Biology and Medicine, October 1, 2002; 227(9): 701 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hamerman Molecular-Based Therapeutic Approaches in Treatment of Anorexia of Aging and Cancer Cachexia J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2002; 57(8): M511 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. O'Neil, A. E. Green, D. E. Edwards, K. F. Swan, T. Gimpel, V. D. Castracane, and M. C. Henson Regulation of Leptin and Leptin Receptor in Baboon Pregnancy: Effects of Advancing Gestation and Fetectomy J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2518 - 2524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Callies, M. Fassnacht, J. C. van Vlijmen, I. Koehler, D. Huebler, M. J. Seibel, W. Arlt, and B. Allolio Dehydroepiandrosterone Replacement in Women with Adrenal Insufficiency: Effects on Body Composition, Serum Leptin, Bone Turnover, and Exercise Capacity J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 1968 - 1972. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Maccario, G. Aimaretti, G. Corneli, C. Gauna, S. Grottoli, M. Bidlingmaier, C. J. Strasburger, C. Dieguez, F. F. Casanueva, and E. Ghigo Short-term fasting abolishes the sex-related difference in GH and leptin secretion in humans Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E411 - E416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.M English, O Mandour, R.P Steeds, M.J Diver, T.H Jones, and K.S Channer Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms Eur. Heart J., June 1, 2000; 21(11): 890 - 894. [Abstract] [PDF]
|
|
|
|
|
|
A. M. Isidori, F. Strollo, M. Morè, M. Caprio, A. Aversa, C. Moretti, G. Frajese, G. Riondino, and A. Fabbri Leptin and Aging: Correlation with Endocrine Changes in Male and Female Healthy Adult Populations of Different Body Weights J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1954 - 1962. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. R. Mann, M. A. Akinbami, K. G. Gould, and V. D. Castracane A Longitudinal Study of Leptin During Development in the Male Rhesus Monkey: The Effect of Body Composition and Season on Circulating Leptin Levels Biol Reprod, February 1, 2000; 62(2): 285 - 291. [Abstract] [Full Text]
|
|
|
|
|
|
M. Rosenbaum and R. L. Leibel Role of Gonadal Steroids in the Sexual Dimorphisms in Body Composition and Circulating Concentrations of Leptin J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 1784 - 1789. [Full Text]
|
|
|
|
 |
|
 F. Machinal, M.-N. Dieudonne, M.-C. Leneveu, R. Pecquery, and Y. Giudicelli In Vivo and in Vitro ob Gene Expression and Leptin Secretion in Rat Adipocytes: Evidence for a Regional Specific Regulation by Sex Steroid Hormones Endocrinology, April 1, 1999; 140(4): 1567 - 1574. [Abstract] [Full Text]
|
|
|
|
|
|
M. L. Ahmed, K. K. L. Ong, D. J. Morrell, L. Cox, N. Drayer, L. Perry, M. A. Preece, and D. B. Dunger Longitudinal Study of Leptin Concentrations during Puberty: Sex Differences and Relationship to Changes in Body Composition J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 899 - 905. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Jeevanandam, C. K. Begay, and S. R. Petersen Plasma Leptin Levels in Trauma Patients: Effect of Adjuvant Recombinant Human Growth Hormone in Intravenously Fed Multiple Trauma Patients JPEN J Parenter Enteral Nutr, November 1, 1998; 22(6): 340 - 346. [Abstract] [PDF]
|
|
|
|
|
|
V. Luukkaa, U. Pesonen, I. Huhtaniemi, A. Lehtonen, R. Tilvis, J. Tuomilehto, M. Koulu, and R. Huupponen Inverse Correlation between Serum Testosterone and Leptin in Men J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3243 - 3246. [Abstract] [Full Text]
|
|
|
|
|
|
M. R. Palmert, S. Radovick, and P. A. Boepple Leptin Levels in Children with Central Precocious Puberty J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2260 - 2265. [Abstract] [Full Text]
|
|
|
|
|
|
X. Casabiell, V. Piñeiro, R. Peino, M. Lage, J. Camiña, R. Gallego, L. G. Vallejo, C. Dieguez, and F. F. Casanueva Gender Differences in Both Spontaneous and Stimulated Leptin Secretion by Human Omental Adipose Tissue in Vitro: Dexamethasone and Estradiol Stimulate Leptin Release in Women, But Not in Men J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 2149 - 2155. [Abstract] [Full Text]
|
|
|
|
|
|
M. R. Palmert, S. Radovick, and P. A. Boepple The Impact of Reversible Gonadal Sex Steroid Suppression on Serum Leptin Concentrations in Children with Central Precocious Puberty J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1091 - 1096. [Abstract] [Full Text]
|
|
|
|
|
|
W. F. Blum, P. Englaro, S. Hanitsch, A. Juul, N. T. Hertel, J. Muller, N. E. Skakkebak, M. L. Heiman, M. Birkett, A. M. Attanasio, et al. Plasma Leptin Levels in Healthy Children and Adolescents: Dependence on Body Mass Index, Body Fat Mass, Gender, Pubertal Stage, and Testosterone J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2904 - 2910. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
