Prenatal Programming: Prenatal Testosterone Excess Impacts Adipocyte Morphology in Sheep

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 548-560-Hyperandrogenic Disorders
Basic/Clinical
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-554
Jacob Scott Moeller*1, Wen Ye1, Vasantha Padmanabhan2 and Almudena Veiga-Lopez3
1University of Michigan, 2Univ of Michigan, Ann Arbor, MI, 3Univ of Michigan Med Schl, Ann Arbor, MI
Prenatal testosterone (T) excess induces maternal hyperinsulinemia and fetal growth retardation, culminating in reproductive and metabolic deficits in female sheep. These sheep manifest insulin resistance and compensatory hyperinsulinemia. Increased adiposity and adipocyte size has been reported to correlate with insulin resistance. Previously, we found prenatal T excess leads to reduced adipocyte size and area at ~21 months of age, similar to lean women with PCOS. The objectives of this study were to determine the relative contribution of androgen and insulin in altering adipocyte size in prenatal T-treated sheep. Prenatal treatment involved administering T propionate (100 mg, i.m.) twice weekly from days 30 to 90 of gestation (T group). Control group (C) received vehicle. Prenatal interventions involved the co-administration of T plus an androgen antagonist (flutamide, 15 mg/kg/day, s.c.; TF group), and T plus an insulin sensitizer (rosiglitazone, 8 mg/day, orally, TR group). Abdominal and subcutaneous adipocytes were collected from adult females (C; n=9, 8; T, n=5, 5; TF, n=8, 8; TR, n=6, 6, respectively), cut into small pieces, and dissociated using collagenase A (Roche; 5 mg/ml). Dissociated adipocytes were imaged and captured under bright field illumination. Area and mean cell diameter were calculated using computerized image analysis (Image-Pro Plus) and differences among groups analyzed using a permutation test based on Kolmogorov-Smirnov statistics with pairwise comparisons. The area (C: 10,856.7±51.4 vs. T: 8,593.1±80.7 μm, p=.055;) and mean cell diameter (C: 114.9±0.3 vs. T: 100.8±0.5 μm, p<.05) were smaller in the T group’s abdominal adipocytes. A similar effect of prenatal T was seen in subcutaneous adipocytes (area: C: 5,225.8±27.6 vs. T: 4,680.2±44.4 μm, p<.05; diameter: C: 79.7±0.2 vs. T: 74.4±0.3 μm, p<.05).  Area (TF:  8,722.4±75.1; TR: 8,567.2±66.3) and mean adipocyte diameter (TF: 100.6±0.5; TR: 101.1±0.4) of the TF or TR group did not differ from either the C or the T group.  Subcutaneous adipocyte area (TF: 4,289.4±33.3; TR: 3,496.8±30.5) and mean diameter (TF: 71.1±0.3; TR: 64.2±0.3) differed (p<.05) from C,  but not the T group. These findings suggest that the effect of prenatal T on adipocyte morphology of both fat depots may be mediated with both androgen and insulin signaling pathways acting in synergy or alternatively via estrogenic actions of T.

Nothing to Disclose: JSM, WY, VP, AV

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Supported by NIH PO1 HD44232.