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Horm Metab Res 2006; 38(5): 330-335
DOI: 10.1055/s-2006-925392
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Circulating Progesterone and Obesity in Men

S.  Blanchette1 , P.  Marceau2 , S.  Biron2 , G.  Brochu2 , A.  Tchernof1, 3
  • 1 Molecular Endocrinology Research Center, Laval University Medical Research Center, Quebec, Canada
  • 2 Department of Surgery, Laval University, Quebec, Canada
  • 3 Department of Nutrition, Laval University, Quebec, Canada
Further Information

Publication History

Received 6 June 2005

Accepted after revision 14 February 2006

Publication Date:
23 May 2006 (online)

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Abstract

Progesterone can be detected in male plasma and has been considered to originate mainly from the adrenals. We have examined the association between circulating progesterone and obesity in a sample of thirty-eight lean to morbidly obese men aged 44.5 ± 9.9 years (BMI: 44.3 ± 12.8 kg/m2). Plasma concentrations of progesterone, 17-OH-progesterone as well as androstendione, testosterone, DHT and DHEA-S were determined. Negative correlations were observed between plasma progesterone levels and body weight (r = - 0.47, p < 0.05), BMI (r = - 0.56, p < 0.001), waist circumference (r = - 0.58, p < 0.001), as well as subcutaneous adipocyte diameter (r = - 0.50, p < 0.05). Plasma levels of 17-OH-progesterone, DHEA-S, androstendione, testosterone and DHT were also negatively associated with body weight, BMI and waist circumference. However, the ratio of 17-OH-progesterone-to-progesterone and androstendione-to-17-OH-progesterone were not related to these variables. A positive correlation was found between circulating progesterone and DHEA-S levels (r = 0.50, p < 0.002 after adjustment for age). Accordingly, using multivariate regression analyses, the best steroid predictor of progesterone level was plasma DHEA-S. Waist circumference was the best predictor of progesterone levels in a multivariate model including steroid concentrations as well as waist circumference, BMI and subcutaneous adipocyte diameter. In conclusion, plasma progesterone was negatively associated with markers of obesity such as BMI, waist circumference and subcutaneous adipocyte diameter in this sample of men. Circulating DHEA-S level was the best steroid correlate of plasma progesterone. We suggest that the low progesterone levels observed in obese men may reflect decreased adrenal C19 steroid production in the adrenal cortex. Further research is needed to confirm this hypothesis.

Key words

Obesity - waist circumference - adipose tissue - progesterone - 17-hydroxyprogesterone - dehydroepiandrosterone

References

  • 1 Vermeulen A. Plasma levels and secretion rate of steroids with anabolic activity in man.  Environ Qual Saf. 1976;  5 171-180
    PubMedGoogle Scholar
  • 2 Tea N T, Castanier M, Roger M. Simultaneous radioimmunoassay of plasma progesterone and 17-hydroxyprogesterone normal values in children, in men and in women throughout the menstrual cycle and in early pregnancy.  J Steroid Biochem. 1975;  6 1509-1516
    CrossrefPubMedGoogle Scholar
  • 3 Vermeulen A, Verdonck L. Radioimmunoassay of 17beta-hydroxy-5alpha-androstan-3-one, 4-androstene-3,17-dione, dehydroepiandrosterone, 17-hydroxyprogesterone and progesterone and its application to the human male plasma.  J Steroid Biochem. 1976;  7 1-10
    CrossrefPubMedGoogle Scholar
  • 4 Lacasa D, Le Liepvre X, Ferre P, Dugail I. Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. potential mechanism for the lipogenic effect of progesterone in adipose tissue.  J Biol Chem. 2001;  276 11 512-11 516
    PubMedGoogle Scholar
  • 5 Wiper-Bergeron N, Wu D, Pope L, Schild-Poulter C, Hache R J. Stimulation of preadipocyte differentiation by steroid through targeting of an HDAC1 complex.  EMBO J. 2003;  22 2135-2145
    CrossrefPubMedGoogle Scholar
  • 6 Björntorp P. Endocrine abnormalities in obesity.  Diabetes Rev. 1997;  5 52-68
    PubMedGoogle Scholar
  • 7 Blanchette S, Blouin K, Richard C, Dupont P, Luu-The V, Tchernof A. Expression and activity of 20-hydroxysteroid dehydrogenase (AKR 1C1) in abdominal subcutaneous and omental adipose tissue in women.  J Clin Endocrinol Metab. 2005;  90 264-270
    PubMedGoogle Scholar
  • 8 Blouin K, Blanchette S, Richard C, Dupont P, Luu-The V, Tchernof A. Expression and activity of steroid aldoketoreductases 1C in omental adipose tissue are positive correlates of adiposity in women.  Am J Physiol Endocrinol Metab. 2005;  288 E398-E404
    CrossrefPubMedGoogle Scholar
  • 9 Tchernof A, Labrie F, Bélanger A, Després J P. Obesity and metabolic complications: contribution of dehydroepiandrosterone and other steroid hormones.  J Endocrinol. 1996;  150 S155-S164
    PubMedGoogle Scholar
  • 10 Salehi M, Ferenczi A, Zumoff B. Obesity and cortisol status.  Horm Metab Res. 2005;  37 193-197
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Marceau P, Biron S, Hould F S, Marceau S, Simard S, Thung S N, Kral J G. Liver pathology and the metabolic syndrome X in severe obesity.  J Clin Endocrinol Metab. 1999;  84 1513-1517
    CrossrefPubMedGoogle Scholar
  • 12 Marceau P, Hould F S, Lebel S, Marceau S, Biron S. Malabsorptive obesity surgery.  Surg Clin North Am. 2001;  81 1113-1127
    CrossrefPubMedGoogle Scholar
  • 13 Rodbell M. Metabolism of isolated fat cells.  J Biol Chem. 1964;  239 375-380
    PubMedGoogle Scholar
  • 14 Nestler J E, McClanahan M A, Clore J N, Blackard W G. Insulin inhibits adrenal 17,20-lyase activity in man.  J Clin Endocrinol Metab. 1992;  74 362-367
    CrossrefPubMedGoogle Scholar
  • 15 Fiet J, Villette J M, Galons H, Boudou P, Burthier J M, Hardy N, Soliman H, Julien R, Vexiau P, Gourmelen M. The application of a new highly-sensitive radioimmunoassay for plasma 21-deoxycortisol to the detection of steroid-21-hydroxylase deficiency.  Ann Clin Biochem. 1994;  31 56-64
    PubMedGoogle Scholar
  • 16 Cristoni S, Cuccato D, Sciannamblo M, Bernardi L R, Biunno I, Gerthoux P, Russo G, Weber G, Mora S. Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoring.  Rapid Commun Mass Spectrom. 2004;  18 77-82
    CrossrefPubMedGoogle Scholar
  • 17 Mendes A M, Madon R J, Flint D J. Effects of cortisol and progesterone on insulin binding and lipogenesis in adipocytes from normal and diabetic rats.  J Endocrinol. 1985;  106 225-231
    PubMedGoogle Scholar
  • 18 Shirling D, Ashby J P, Baird J D. Effect of progesterone on lipid metabolism in the intact rat.  J Endocrinol. 1981;  90 285-294
    PubMedGoogle Scholar
  • 19 Tchernof A, Labrie F. Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies.  Eur J Endocrinol. 2004;  151 1-14
    CrossrefPubMedGoogle Scholar
  • 20 l'Allemand D, Schmidt S, Rousson V, Brabant G, Gasser T, Gruters A. Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche.  Eur J Endocrinol. 2002;  146 537-543
    CrossrefPubMedGoogle Scholar
  • 21 Kurtz B R, Givens J R, Komindr S, Stevens M D, Karas J G, Bittle J B, Judge D, Kitabchi A E. Maintenance of normal circulating levels of delta-4- androstendione and dehydroepiandrosterone in simple obesity despite increased metabolic clearance rates: evidence for a servo-control mechanism.  J Clin Endocrinol Metab. 1987;  64 1261-1267
    PubMedGoogle Scholar
  • 22 Fehér T, Halmy L. Dehydroepiandrosterone and dehydroepiandrosterone sulfate dynamics in obesity.  Can J Biochem. 1975;  53 215-222
    PubMedGoogle Scholar
  • 23 Kirschner M A, Samojlik E, Silber D. A comparison of androgen production and clearance in hirsute and obese women.  J Steroid Biochem. 1983;  19 607-614
    CrossrefPubMedGoogle Scholar
  • 24 Tchernof A, Després J P, Bélanger A, Dupont A, Prud'homme D, Moorjani S, Lupien P J, Labrie F. Reduced testosterone and adrenal C19 steroid levels in obese men.  Metabolism. 1995;  44 513-519
    CrossrefPubMedGoogle Scholar
  • 25 Abbasi A, Duthie Jr E H , Sheldahl L, Wilson C, Sasse E, Rudman I, Mattson D E. Association of dehydroepiandrosterone sulfate, body composition, and physical fitness in independent community-dwelling older men and women.  J Am Geriatr Soc. 1998;  46 263-273
    PubMedGoogle Scholar
  • 26 Couillard C, Gagnon J, Bergeron J, Leon A S, Rao D C, Skinner J S, Wilmore J H, Després J P, Bouchard C. Contribution of body fatness and adipose tissue distribution to the age variation in plasma steroid hormone concentrations in men: the HERITAGE family study.  J Clin Endocrinol Metab. 2000;  85 1026-1031
    CrossrefPubMedGoogle Scholar
  • 27 de Pergola G, Giagulli V A, Garruti G, Cospite M R, Giorgino F, Cignarelli M, Giorgino R. Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index.  Metabolism. 1991;  40 187-190
    CrossrefPubMedGoogle Scholar
  • 28 Després J P, Moorjani S, Ferland M, Tremblay Y, Lupien P J, Nadeau A, Pinault S, Thériault G, Bouchard C. Adipose tissue distribution and plasma lipoprotein levels in obese women: importance of intra-abdominal fat.  Arteriosclerosis. 1989;  9 203-210
    CrossrefPubMedGoogle Scholar
  • 29 Moghetti P, Castello R, Negri C, Tosi F, Spiazzi G G, Brun E, Balducci R, Toscano V, Muggeo M. Insulin infusion amplifies 17a-hydroxycorticosteroid intermediates responses to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity.  J Clin Endocrinol Metab. 1996;  81 881-886
    CrossrefPubMedGoogle Scholar
  • 30 Ueshiba H, Shimizu Y, Hiroi N, Yakushiji F, Shimojo M, Tsuboi K, Miyachi Y. Decreased steroidogenic enzyme 17,20-lyase and increased 17-hydroxylase activities in type 2 diabetes mellitus.  Eur J Endocrinol. 2002;  146 375-380
    CrossrefPubMedGoogle Scholar
  • 31 Guido M, Romualdi D, Suriano R, Giuliani M, Costantini B, Apa R, Lanzone A. Effect of pioglitazone treatment on the adrenal androgen response to corticotrophin in obese patients with polycystic ovary syndrome.  Hum Reprod. 2004;  19 534-539
    CrossrefPubMedGoogle Scholar
  • 32 Considine R V, Caro J F. Leptin: genes, concepts and clinical perspective.  Horm Res. 1996;  46 249-256
    PubMedGoogle Scholar
  • 33 Kruse M, Bornstein S R, Uhlmann K, Paeth G, Scherbaum W A. Leptin down-regulates the steroid producing system in the adrenal.  Endocr Res. 1998;  24 587-590
    PubMedGoogle Scholar
  • 34 Harle P, Pongratz G, Weidler C, Buttner R, Scholmerich J, Straub R H. Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis.  Ann Rheum Dis. 2004;  63 809-816
    CrossrefPubMedGoogle Scholar
  • 35 Bornstein S R, Uhlmann K, Haidan A, Ehrhart-Bornstein M, Scherbaum W A. Evidence for a novel peripheral action of leptin as a metabolic signal to the adrenal gland: leptin inhibits cortisol release directly.  Diabetes. 1997;  46 1235-1238
    CrossrefPubMedGoogle Scholar
  • 36 Wilson M E, Fisher J, Brown J. Chronic subcutaneous leptin infusion diminishes the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in female rhesus monkeys.  Physiol Behav. 2005;  84 449-458
    CrossrefPubMedGoogle Scholar
  • 37 Salzmann C, Otis M, Long H, Roberge C, Gallo-Payet N, Walker C D. Inhibition of steroidogenic response to adrenocorticotropin by leptin: implications for the adrenal response to maternal separation in neonatal rats.  Endocrinology. 2004;  145 1810-1822
    PubMedGoogle Scholar
  • 38 Jaattela M, Ilvesmaki V, Voutilainen R, Stenman U H, Saksela E. Tumor necrosis factor as a potent inhibitor of adrenocorticotropin-induced cortisol production and steroidogenic P450 enzyme gene expression in cultured human fetal adrenal cells.  Endocrinology. 1991;  128 623-629
    PubMedGoogle Scholar
  • 39 Borst S E. The role of TNF-alpha in insulin resistance.  Endocrine. 2004;  23 177-182
    CrossrefPubMedGoogle Scholar
  • 40 Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K, Fujii M, Tsuchihashi K, Goto H, Nakatani K, Yano Y. Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus.  J Clin Endocrinol Metab. 1998;  83 859-862
    CrossrefPubMedGoogle Scholar
  • 41 Fain J N, Bahouth S W, Madan A K. TNFalpha release by the nonfat cells of human adipose tissue.  Int J Obes Relat Metab Disord. 2004;  28 616-622
    CrossrefPubMedGoogle Scholar
  • 42 Weisberg S P, McCann D, Desai M, Rosenbaum M, Leibel R L, Ferrante Jr A W. Obesity is associated with macrophage accumulation in adipose tissue.  J Clin Invest. 2003;  112 1796-1808
    CrossrefPubMedGoogle Scholar
  • 43 Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, Langenbach J, Willenberg H S, Barthel A, Hauner H, McCann S M, Scherbaum W A, Bornstein S R. Human adipocytes secrete mineralocorticoid-releasing factors.  Proc Natl Acad Sci U S A. 2003;  100 14 211-14 216
    PubMedGoogle Scholar
  • 44 Lavallée B, Provost P R, Nestler J E, Kahwash Z, Bélanger A. Effect of insulin on serum levels of dehydroepiandrosterone metabolites in men.  Clin Endocrinol. 1997;  46 93-100
    CrossrefPubMedGoogle Scholar
  • 45 Bélanger C, Luu-The V, Dupont P, Tchernof A. Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity.  Horm Metab Res. 2002;  34 737-745
    Article in Thieme ConnectPubMedGoogle Scholar

André Tchernof, Ph. D.

Molecular Endocrinology Research Center · Department of Nutrition · Laval University Medical Center

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Email: andre.tchernof@crchul.ulaval.ca