Our previous study suggested that hypothyroidism in Goto-Kakizaki (GK) rats with insulin resistance and type 2 diabtetes elevates
their serum testosterone and luteinizing hormone (LH) levels and ovarian LH receptor messenger RNA (mRNA) expression. The
present study assessed the effects of troglitazone (Tro), an insulin-sensitizing agent, on these hypothyroidism-induced hormonal
changes in GK rats. GK and normal (Wistar strain) female rats were thyroidectomized (Tx) and then injected with 5 IU of equine
chorionic gonadotropin (eCG) for 5 d starting 1 wk after thyroidectomy (the control groups). In the test groups, Tx GK and
Wistar rats were injected with both eCG and Tro (100 mg kg
−1) po for 5 d. Tro treatment had no effect on the elevated LH serum levels in eCG-treated Tx GK rats but suppressed their enhanced
serum testosterone levels as well as significantly decreasing their LH receptor mRNA expression. Tro lowered testosterone
and LH receptor mRNA levels in cultured theca cells. These results indicate that Tro lowers the elevated testosterone secretion
and ovarian LH receptor mRNA expression that is induced in GK rats by Tx and gonadotropin treatment, which suggests that insulin
resistance may be involved in enhancing testosterone production and LH receptor expression in the ovary.
Key Words Troglitazone - testosterone - luteinizing hormone receptor - hypothyroidism - insulin resistance - Goto-Kakizaki (GK) rat