Changes in ovarian steroidogenesis in insulin-resistant, type 2 diabetic Goto-Kakizaki rats after thyroidectomy and gonadotropin treatment

The present study used thyroidectomized insulin-resistant, type 2 diabetic Goto-Kakizaki (GK) rats to assess whether insulin resistance and hypothyroidism modulate ovarian physiology. Animals were treated with daily injections of 5 IU equine chorionic gonadotropin for 5 days starting 1 week after thyroidectomy. Control groups included rats of GK and control (Wistar) strains treated only with equine chorionic gonadotropin or thyroidectomy, or with no treatment (intact). In Wistar rats, equine chorionic gonadotropin injections tended to increase the serum concentrations of luteinizing hormone (LH) and testosterone more in the thyroidectomy group than in intact rats. Similar changes in LH and testosterone were observed in the thyroidectomy + equine chorionic gonadotropin and equine chorionic gonadotropin groups of GK rats, but the LH and testosterone levels in the thyroidectomy + equine chorionic gonadotropin group were significantly higher in GK rats. Expression of ovarian LH receptor messenger RNA (mRNA) was enhanced by thyroidectomy. The LH receptor mRNA levels were significantly higher in the thyroidectomy + equine chorionic gonadotropin group of GK rats than in the corresponding group of control rats. These results indicate that hypothyroidism in animals with insulin resistance and type 2 diabetes promotes LH and testosterone secretions, and suggests that the enhanced-testosterone levels is partially mediated by the enhancement of LH receptor expression and an increase in the serum level of LH.