Obesity alters the estrogen-induced luteinizing hormone surge in ovariectomized ewes†.

Obesity is a leading health issue with a negative effect on fertility, but the complexity of the relationship between obesity and fertility requires further study. Santoro and colleagues have characterized the metabolic environment of obesity and the development of reprometabolic syndrome. Due to the reproductive similarities between ewes and women, we use ovariectomized ewes as a translational model of reprometabolic syndrome and tested whether obesity alters the estradiol-17β (E2)-induced luteinizing hormone (LH) surge. Each ovariectomized ewe serves as her own biological control during the three phases of the study: normal weight (phase 1), obese (phase 2), and a return to normal weight (phase 3). Ewes were weighed weekly, and 12th rib fat thickness was measured as a proxy for body condition score. During each of the three phases of the study, following an intramuscular injection of 25 μg of E2, serial blood samples were collected, and serum LH concentrations were measured by radioimmunoassay. The peak concentration and timing of the LH surge are significantly lower and delayed in obese ewes in phase 2 as compared to phases 1 and 3. Our results suggest that the mechanisms that underlie the pathological effects of obesity and reprometabolic syndrome on the E2-induced LH surge are similar in ewes and women. Therefore, ewes can serve as a model for parsing the relative roles of diminished hypothalamic and pituitary sensitivity to E2, resulting in a reduced and delayed LH surge associated with obesity and reprometabolic syndrome in women.