Effect of chronic thyroid hormone treatment on cycling, ovulation, serum reproductive hormones and ovarian LH and prolactin receptors in rats

We studied the effect on cycling, ovulation and hormone secretion of a chronic thyroxine treatment (HT, 1 mg/kg, S.C., daily, initiated at oestrus) on female rats. HT rats showed normal 4-day vaginal cycles on the first three cycles after initiation of the treatment, but on the fourth cycle had a prolonged oestrus and subsequently entered in constant di-oestrus. In spite of the normal vaginal cycles only 66%, 50%, 33% and 10% of the HT rats ovulated on cycles 1 to 4 respectively. In contrast, during cycles 2 and 3, ovulating HT rats shed a significantly greater number of ova than controls. Hormones were measured at 12.00 and 18.00 h (pre-ovulatory) on prooestrus and at 11.00 h on oestrus. HT ovulating rats had normal LH levels on the first two cycles, but low levels on the third one, while non-ovulating HT rats had low preovulatory LH levels. Serum FSH concentrations were elevated in all the HT rats on cycles 1 and 2 and on pro-oestrus morning in cycle 3 and may have been responsible for the increase in ovulation rate. On oestrus, ovulating HT rats had higher FSH values than nonovulating ones. Serum prolactin levels were similar to controls in all the HT rats on cycle 1, but on the subsequent cycles pre-ovulatory levels were lower than controls in all the HT rats, while values were increased in the non-ovulating HT rats on the third and fourth oestrus mornings. Pro-oestrous serum oestradiol concentrations in all the HT rats were not different from controls on cycles 1 and 2 and diminished on 3 and 4. Oestrous levels were significantly lower on the cycle 1 and only on the nonovulating HT rats on cycle 2. Serum progesterone levels had values similar to those of FSH, with increased values in the first two cycles. Serum corticosterone levels were increased in the mornings of cycles 2 and 3, but values were normal on the fourth one. Ovarian prolactin and LH receptor mRNAs, measured on HT rats on the third prooestrus by Northern blotting, showed significant increases in all the majoritary molecular forms (2.5 and 7 kb for LH receptor and 0.9, 2.9-3, 5 and 10 kb for the prolactin receptor) with respect to control pro-oestrous rats. These results show a progressive disruption of cycling, ovulation and hormonal secretion after the initiation of a chronic thyroid hormone treatment in rats, which eventually lead to an anovulatory state. These results may be of importance for the interpretation of the reproductive disfunctions provoked by hyperthyroidism in women.