Effect of TSH on aromatase expression of ovarian granulosa cells in obese mice.

Abstract

Purpose: Aromatase plays an important role in ovarian development, the normal progress of the menstrual cycle, and fertility status. Elevated aromatase activity is linked to obesity. There is a bidirectional relationship between obesity and thyroid function. Few studies have investigated the relationship between TSH and ovarian aromatase in obesity. Our aim was to investigate the effect of TSH on aromatase expression of ovarian granulosa cells in obese mice.

Methods: Female mice pups were divided into an obesity group and a control group. Obese parameters and the time of pubertal onset were recorded. At the age of 5 weeks, blood and tissues were obtained. Serum aromatase and hormone concentrations were measured using ELISA. The granulosa cells were isolated and exposed to variable concentrations (0 μM, 1 μM, 10 μM, 100 μM) of TSH. The expression of CYP19A1 mRNA and protein were assessed via RT-qPCR and western blot.

Results: In female mice, body weight, Lee's obesity index, and serum levels of E2, aromatase, and TSH were significantly higher in the obesity group compared to the control group, whereas the time of pubertal onset and serum T3 and T4 concentrations were significantly lower (all P < 0.001). In granulosa cells, the expression of CYP19A1 mRNA in the obesity group was lower than that in the control group at 1 μM and 100 μM concentrations of TSH (both P < 0.001). The expression of CYP19A1 protein in the obesity group was higher than that in the control group after TSH stimulation (P = 0.014, P < 0.001, and P = 0.004, respectively). With the increase of TSH concentrations, the expression of CYP19A1 mRNA and protein in the two groups significantly increased (all P < 0.001).

Conclusion: Early puberty and elevated serum aromatase and TSH levels were found in obese female mice. In the granulosa cells of obese mice, TSH directly regulates aromatase expression in a dose-dependent manner.