Abstract
Introduction:
Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with polycystic ovary syndrome (PCOS) women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic β-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI).
Objective:
To determine whether PA females have altered body fat distribution.
Design:
Five early-treated PA (EPA), five late-treated PA (LPA) and five control adult female monkeys underwent somatometrics, dual-X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Five control and five EPA females underwent an intravenous glucose tolerance test to assess the relationship between body composition and glucoregulation.
Results:
There were no differences in age, weight, BMI or somatometrics. LPA females had ∼20% greater DXA-determined total fat and percent body fat, as well as total and percent abdominal fat than EPA or control females (P⩽0.05). LPA females also had ∼40% more CT-determined non-visceral abdominal fat than EPA or control females (P⩽0.05). The volume of visceral fat was similar among the three groups. EPA (R2=0.94, P⩽0.01) and LPA (R2=0.53, P=0.16) females had a positive relationship between visceral fat and BMI, although not significant for LPA females. Conversely, control females had a positive relationship between non-visceral fat and BMI (R2=0.98, P⩽0.001). There was a positive relationship between basal insulin and total body (R2=0.95, P⩽0.007), total abdominal (R2=0.81, P⩽0.04) and visceral (R2=0.82, P⩽0.03) fat quantities in EPA, but not control females.
Conclusions:
Prenatal androgenization in female rhesus monkeys induces adiposity-dependent visceral fat accumulation, and late gestation androgenization causes increased total body and non-visceral fat mass. Early gestation androgenization induces visceral fat-dependent hyperinsulinemia. The relationship between the timing of prenatal androgen exposure and body composition phenotypes in this nonhuman primate model for PCOS may provide insight into the heterogeneity of metabolic defects found in PCOS women.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Dunaif A, Finegood DT . Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81: 942–947.
Dunaif A . Insulin action in the polycystic ovary syndrome. Endocrinol Metab Clin North Am 1999; 28: 341–359.
Eisner JR, Dumesic DA, Kemnitz JW, Abbott DH . Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys. J Clin Endocrinol Metab 2000; 85: 1206–1210.
Dumesic DA, Schramm RD, Abbott DH . Early origins of polycystic ovary syndrome. Reprod Fertil Dev 2005; 17: 349–360.
Abbott DH, Barnett DK, Bruns CM, Dumesic DA . Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update 2005; 11: 357–374.
Douchi T, Ijuin H, Nakamura S, Oki T, Yamamoto S, Nagata Y . Body fat distribution in women with polycystic ovary syndrome. Obstet Gynecol 1995; 86: 516–519.
Kirchengast S, Huber J . Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 2001; 16: 1255–1260.
Yildirim B, Sabir N, Kaleli B . Relation of intra-abdominal fat distribution to metabolic disorders in nonobese patients with polycystic ovary syndrome. Fertil Steril 2003; 79: 1358–1364.
Puder JJ, Varga S, Kraenzlin M, De Geyter C, Keller U, Muller B . Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance. J Clin Endocrinol Metab 2005; 90: 6014–6021.
Eisner JR, Dumesic DA, Kemnitz JW, Colman RJ, Abbott DH . Increased adiposity in female rhesus monkeys exposed to androgen excess during early gestation. Obes Res 2003; 11: 279–286.
Goy RW, Kemnitz JW . Early, persistent, and delayed effects of virilizing substances delivered transplacentally to female rhesus fetuses. In: Weiss B (ed). Application of Behavioral Pharmacology in Toxicology. Raven Press: New York, 1983; pp: 303–314.
Goy RW, Robinson JA . Prenatal exposure of rhesus monkeys to patent androgens: morphological, behavioral, and physiological consequences. Banbury Rep 1982; 11: 355–378.
Kemnitz JW, Elson DF, Roecker EB, Baum ST, Bergman RN, Meglasson MD . Pioglitazone increases insulin sensitivity, reduces blood glucose, insulin, and lipid levels, and lowers blood pressure, in obese, insulin-resistant rhesus monkeys. Diabetes 1994; 43: 204–211.
Dumesic DA, Abbott DH, Eisner JR, Goy RW . Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood. Fertil Steril 1997; 67: 155–163.
Dumesic DA, Schramm RD, Peterson E, Paprocki AM, Zhou R, Abbott DH . Impaired developmental competence of oocytes in adult prenatally androgenized female rhesus monkeys undergoing gonadotropin stimulation for in vitro fertilization. J Clin Endocrinol Metab 2002; 87: 1111–1119.
Abbott DH, Dumesic DA, Eisner JR, Colman RJ, Kemnitz JW . Insights into the development of PCOS from studies of prenatally androgenized female rhesus monkeys. Trends Endocrinol Metab 1998; 9: 62–67.
Jen KL, Hansen BC, Metzger BL . Adiposity, anthropometric measures, and plasma insulin levels of rhesus monkeys. Int J Obes 1985; 9: 213–224.
Colman RJ, Hudson JC, Barden HS, Kemnitz JW . A comparison of dual-energy X-ray absorptiometry and somatometrics for determining body fat in rhesus macaques. Obes Res 1999; 7: 90–96.
Sokal RR, Rohlf FJ . Biometry: The Principles and Practice of Statistics in Biological Research,4th edn. W. H. Freeman and Co: New York, 1995; 413–422.
Kvist H, Chowdhury B, Grangard U, Tylen U, Sjostrom L . Total and visceral adipose-tissue volumes derived from measurements with computed tomography in adult men and women: predictive equations. Am J Clin Nutr 1988; 48: 1351–1361.
Kemnitz JW, Goy RW, Flitsch TJ, Lohmiller JJ, Robinson JA . Obesity in male and female rhesus monkeys: fat distribution, glucoregulation, and serum androgen levels. J Clin Endocrinol Metab 1989; 69: 287–293.
Hickey T, Chandy A, Norman RJ . The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87: 161–165.
Goodarzi MO, Shah NA, Antoine HJ, Pall M, Guo X, Azziz R . Variants in the 5alpha-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women. J Clin Endocrinol Metab 2006; 91: 4085–4089.
Lebovitz HE, Banerji MA . Point: visceral adiposity is causally related to insulin resistance. Diabetes Care 2005; 28: 2322–2325.
Venkatesan AM, Dunaif A, Corbould A . Insulin resistance in polycystic ovary syndrome: progress and paradoxes. Recent Prog Horm Res 2001; 56: 295–308.
Holte J, Bergh T, Berne C, Berglund L, Lithell H . Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance. J Clin Endocrinol Metab 1994; 78: 1052–1058.
Dunaif A, Segal KR, Futterweit W, Dobrjansky A . Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38: 1165–1174.
Abbott DH, Bruns CM, Barnett DK, Zhou R, Colman RJ, Kemnitz JW et al. Metabolic and reproductive consequences of prenatal testosterone exposure. Abstract S34-1 presented at the 85th Annual Meeting of the Endocrine Society, June 19-22, 2003, Philadelphia, PA.
Acknowledgements
We gratefully acknowledge Mike Dobbert, Jim Turk, Kerri Hable, Peggy Helwig, Amy Lange, John Garry, Deborah Barnett, PhD, Kurt Sladky, DVM, and Lisa Forrest, DVM for assistance with procedures. We also thank Ron Gangnon and Mike Evans for statistical support, Fritz Wegner and the Assay Services of WNPRC for assay support, and the veterinary and animal care staff at WNPRC. This work was supported by NIH grants R01 RR013635, T32 AG000268, P50 HD044405 and P51 RR000167. This research was conducted at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459 and RR020141.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bruns, C., Baum, S., Colman, R. et al. Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome. Int J Obes 31, 1579–1585 (2007). https://doi.org/10.1038/sj.ijo.0803638
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijo.0803638
Keywords
This article is cited by
-
Applying the adverse outcome pathway concept for assessing non-monotonic dose responses: biphasic effect of bis(2-ethylhexyl) phthalate (DEHP) on testosterone levels
Archives of Toxicology (2023)
-
Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood—longitudinal analysis of BMI data from birth to age 46 in cases of PCOS
International Journal of Obesity (2019)
-
Polycystic ovary syndrome resembling histopathological alterations in ovaries from prenatal androgenized female rats
Journal of Ovarian Research (2012)
-
Nonhuman primates as models for human adrenal androgen production: Function and dysfunction
Reviews in Endocrine and Metabolic Disorders (2009)
-
Polycystic ovary syndrome and its developmental origins
Reviews in Endocrine and Metabolic Disorders (2007)