Visceral Fat Removal Improves Steroid-induced LH Surge in Middle-Aged Female Rats

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 515-547-Female Reproductive Endocrinology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-547
Yan SUN*1, Tomoko Inagaki1, Djibril Keita2, Jun Shu1 and Genevieve Neal-Perry1
1Albert Einstein College of Medicine, Bronx, NY, 2Hunter College, Manhattan, NY
Recent data suggests that increased adiposity disrupts estradiol (E2)-positive feedback effects on the hypothalamus-pituitary (HP) axis of females. Although as much as 75% of perimenopausal and menopausal women are obese, the effect of increasing visceral adiposity (metabolically active fat) on transition of females into reproductive senescence is minimally studied. Female reproductive senescence in rat is also characterized by reduced responsiveness to E2 positive feedback and heralded by a significantly delayed and attenuated LH surge. Of interest several studies suggest that moderate caloric restriction delays the transition into reproductive senescence in female rodents and delays age-related infertility. We hypothesize that age-related accrual of metabolic fat and the associated chronic inflammatory state advances the onset of female reproductive senescence. To test this hypothesis we surgically removed metabolically active fat (visceral, perinephric and gonadal fat pads) in young adults (5-6 month old) and then determined if middle-aged females generate an appropriately timed and high amplitude LH surge under E2 positive feedback conditions. Methods: Young female rats were subjected to the surgical removal of visceral fat, perinephric, and gonadal fat pads (n=5) or sham surgery (n=10). Females were then housed with free access to chow and water and monthly body weight assessed. At 9-10 months old weight, fat distribution and glucose tolerance tests (GTT) were performed before females were ovariectomized (OVX), primed with a regime of E2 and progesterone (P) that reliably induces a  LH surge and outfitted with jugular vein catheters (JVC) for serial blood sampling. Starting at 1100 hr on the day of the expected LH surge, blood samples were collected every 1-2 hrs for plasma LH determination. Student’s t-test was used for statistical analysis. Data are reported as mean ± SEM. Results: There was no significant difference in the weight, fat distribution, or GTT in 9 month old females subject to sham and VF surgery as mid reproductive aged adults. A standard regimen of Compared to sham treated females surgical removal of metabolically active fat in young females resulted in greater than a 3 and 1.5 fold increase of peak (2.8±0.8 vs. 8.8±1.6; P=0.003) and total LH release (area under the curve; 1231±273 vs. 2805±677 ng/ml/hr; P=0.07), respectively, as well as the advancement of the onset (9.1±0.3 vs. 7.5±0.5; P=0.009) of the LH surge in middle-aged rats. A similar effect was not observed when middle-aged (11-12 months) females were subjected to sham and VF surgery after a two week recovery period. Conclusion:  These data suggest that metabolically active fat attenuates the responsiveness of the HP-axis to E2-positive feedback and may accelerate the transition into reproductive senescence.

Nothing to Disclose: YS, TI, DK, JS, GN

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Sources of Research Support: Eunice Kennedy Shriver NICHD/NIH through cooperative agreement U54 HD058155, as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research and by the Department of Obstetrics & Gynecology and Women’s Health, Albert Einstein College of Medicine.
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