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. 2011 Mar;208(3):293-300.
doi: 10.1677/JOE-10-0263. Epub 2010 Dec 20.

Prenatal androgen treatment alters body composition and glucose homeostasis in male rats

Milos Lazic  1 , Fraser Aird, Jon E Levine, Andrea Dunaif
Affiliations

Prenatal androgen treatment alters body composition and glucose homeostasis in male rats

Milos Lazic et al. J Endocrinol. 2011 Mar.

Abstract

Prenatal androgen produces many reproductive and metabolic features of polycystic ovary syndrome in female rodents, sheep, and monkeys. We investigated the impact of such prenatal treatment in adult male rats. Pregnant dams received free testosterone (T; aromatizable androgen), dihydrotestosterone (D; nonaromatizable androgen), or vehicle control (C) on embryonic days 16-19. Neither of the prenatal androgen treatments resulted in increased body weight from weaning to age 65 days in males. However, at 65 days, there were significant increases in retroperitoneal (P < 0.001 T versus C; P < 0.05 D versus C), epididymal (P < 0.05 T versus C), and subcutaneous (P < 0.01 T versus C) fat pads in prenatally androgenized males. While both androgens altered body composition, subcutaneous fat depots increased only in T males. T males had elevated glucose levels (P < 0.01) compared to C males. There were no differences among the three groups in insulin sensitivity, circulating lipid and leptin levels, or hepatic triglyceride content. Real-time PCR analysis of insulin signaling pathway genes in retroperitoneal fat revealed a transcriptional downregulation of adipsin and insulin receptor substrate-1 in T and α-1D adrenergic receptor in D compared to C males. We conclude that transient exposure to androgen excess in utero increases body fat in adult male rats. Only T males exhibit increased circulating glucose levels and subcutaneous fat suggesting that these changes may be mediated by aromatization of androgen to estrogen rather than by direct androgenic actions.

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Conflict of interest statement

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of research reported.

Figures

Figure 1
Figure 1
Study schema with the number of animals used in each experiment. IPITT, intraperitoneal insulin tolerance test; IPGTT, intraperitoneal glucose tolerance test; SAL, saline baseline; INS, insulin stimulated.
Figure 2
Figure 2
Body weight and body composition. (A) There were no significant differences in BW among control (C; open squares), testosterone (T; black triangles) and dihydrotestosterone (D; black circles) males. (B) Body composition: T males (striped bars) had significantly increased retroperitoneal, epididymal and sc fat pad weights compared to C males (open bars). D males (black bars) had significantly increased retroperitoneal fat pad weight compared to C males. Values are mean ± SEM. C n=16, T n=15, D n=16. *P<0.05, **P<0.01, ***P<0.001 vs C. †P<0.05 T vs D. (C) Representative MRI axial images of visceral area (renal section) in C, T and D males showed a modest increase in retroperitoneal fat content in D compared to C males and a more striking increase in both mesenteric and retroperitoneal fat depots in T compared to C males; 1) retroperitoneal, 2) mesenteric and 3) sc fat.
Figure 3
Figure 3
Biochemical changes. (A) Serum glucose levels were significantly increased in T (striped bars) compared to C males (open bars), **Pn=17, T n=14, D n=19.
Figure 4
Figure 4
Dynamic testing. There were no significant differences in: (A) glucose and (B) insulin levels during IPGTT; (C) percent basal glucose during IPITT among C (open squares), T (black triangles) and D males (black circles). Values are mean ± SEM. C n=16, T n=13, D n=18.
Figure 5
Figure 5
Insulin signaling (represented as a phospho-AKT: AKT ratio) after 10 min ± ip insulin (5U). No differences in insulin action were detected in (A) skeletal muscle, (B) liver and (C) retroperitoneal fat among C (open bars), T (striped bars) and D males (black bars). Tissue-specific representative Western Blot images of phospho-AKT are shown above the figures. Values are mean ± SEM. C n=8 saline, n=5 insulin; T n=8 saline, n=6 insulin; D n=8 saline, n=6 insulin.
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