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 o estrus) on female rats. HT rats showed normal 4-day vaginal cycles on the first three cycles after initiation of the treatment, but on the f ourth cycle had a prolonged oestrus and subsequently entered in consta nt 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 co ntrast, during cycles 2 and 3, ovulating HT rats shed a significantly greater number of ova than controls. Hormones were measured at 12.00 a nd 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 preovulat ory LH levels. Serum FSH concentrations were elevated in all the HT ra ts on cycles 1 and 2 and on pro-oestrus morning in cycle 3 and may hav e been responsible for the increase in ovulation rate. On oestrus, ovu lating HT rats had higher FSH values than non-ovulating ones. Serum pr olactin levels were similar to controls in all the HT rats on cycle 1, but on the subsequent cycles pre-ovulatory levels were lower than con trols in all the HT rats, while values were increased in the non-ovula ting HT rats on the third and fourth oestrus mornings. Pro-oestrous se rum oestradiol concentrations in all the HT rats were not different fr om controls on cycles 1 and 2 and diminished on 3 and 4. Oestrous leve ls were significantly lower on the cycle 1 and only on the non-ovulati ng HT rats on cycle 2. Serum progesterone levels had values similar to those of FSH, with increased values in the first two cycles. Serum co rticosterone levels were increased in the mornings of cycles 2 and 3, but values were normal on the fourth one. Ovarian prolactin and LH rec eptor mRNAs, measured on HT rats on the third prooestrus by Northern b lotting, 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 th e prolactin receptor) with respect to control pro-oestrous rats. These results show a progressive disruption of cycling, ovulation and hormo nal secretion after the initiation of a chronic thyroid hormone treatm ent in rats, which eventually lead to an anovulatory state. These resu lts may be of importance for the interpretation of the reproductive di sfunctions provoked by hyperthyroidism in women.