EFFECTS OF AGE AND OVARIAN FUNCTION ON THE PITUITARY–THYROID SYSTEM IN FEMALE RATS

Abstract

SUMMARY The effects of ovariectomy and ovariectomy and treatment with oestradiol benzoate (OB) on the basal concentration of thyrotrophin (TSH), the total concentrations and concentrations of free tri-iodothyronine (T3) and thyroxine (T4), and the concentrations of TSH, T3 and T4 observed after treatment with thyrotrophin releasing hormone (TRH) were studied in old (16–17 months of age) constant oestrous and young (3–4 months of age) oestrous rats. The untreated old control rats had significantly (P< 0·001) lower basal total T4 concentrations and percentage and absolute concentrations of free T4 and lower percentage and absolute concentrations of free T3 than untreated young rats. The basal levels of TSH in these two groups were similar and the increases in TSH after injection of TRH were identical. Two weeks after ovariectomy, no significant additional differences in hormone concentrations between old and young rats were observed. However, release of TSH induced by TRH was increased by three- to fourfold in old rats after ovariectomy compared with nine- to tenfold in young ovariectomized rats (P<0·01). Basal T4 concentrations remained unchanged in old ovariectomized rats treated for 7 days with 2 μg OB/day compared with both intact and ovariectomized rats. However, T4 concentrations in OB-treated young rats were significantly (P<0·001) reduced. Treatment with OB significantly increased both basal and TRH-induced T3 and TSH levels in old and young rats although the young rats showed a greater response (P<0·001). Two hours after injection of TRH, serum T3 concentrations in old rats increased only after OB treatment and not after ovariectomy alone or in intact rats, whereas T3 concentrations rose in all three groups of young animals. These results indicate that (1) older female rats have lower total T4, free T4 and free T3 concentrations and a lower TSH response to TRH, (2) OB treatment in young rats suppresses serum T4 but increases serum T3 and results in a greater TSH response to TRH and (3) at least one of the mechanisms accounting for the alterations in thyroid function observed in the older female rat, in addition to possible concomitant primary thyroid gland hypofunction, is a hyporesponsiveness of pituitary thyrotrophs to both endogenous negative feedback signals from low serum thyroid hormone concentrations and exogenous TRH stimulation.