The effect of aging on the release of gonadotropin-releasing hormone (GnRH) in vitro and of luteinizing hormone (LH) both in vivo and in vitro in ovariectomized (Ovx) rats was studied. Old (21–24 months) and young (3–4 months) rats were Ovx before use. They were injected subcutaneously with estradiol benzoate (25 µg/kg) or sesame oil for 3 days and then challenged with GnRH (0.5,2 or 10 µg/kg) via a jugular catheter. Blood samples were collected immediately before and at 5, 10, 20, 40 and 60 min following GnRH injection. For in vitro study, Ovx rats were decapitated. The anterior pituitary glands (APs) were incubated with GnRH (0.1 or 10 nM) and estradiol (0, 0.1, 1 or 10 nM) at 37 ^¤C for 30 min. The mediobasal hypothalamus was superfused with Locke’s solution at 37 °C for 210 min, and stimulated with 60 mM KCl at 90 and 150 min. The medium samples were collected at 10-min intervals. Concentrations of GnRH and LH in plasma and medium samples were measured by radioimmunoassay. In all rats, the basal and GnRH-stimulated levels of plasma LH were lower in old than in young rats. The spontaneous release of LH in vitro from APs of Ovx rats was increased by aging, whereas GnRH-stimulated release of LH in vitro was lower in old than in young animals. The potassium-stimulated, but not spontaneous, release of GnRH was lower in old than in young Ovx rats. These results suggest that the reduction of plasma LH level in female rats during aging is in part due to a decrease in the K⁺-stimulated release of GnRH, and a reduction of pituitary responsiveness to GnRH and estradiol.

Effect of estradiol on the spontaneous and thyrotropin-releasing hormone (TRH)-stimulated release of prolactin (PRL) and thyrotropin (TSH) in young and aged ovariectomized (Ovx) rats was investigated. Old (22–26 months) and young (3 months) female rats were Ovx 3 weeks before use. They were injected subcutaneously with estradiol benzoate (EB, 25 µg/kg) or sesame oil for 3 days and were catheterized via the right jugular vein. Twenty hours after the last administration of EB, rats were injected with TRH (10 µg/kg) through the catheter. Blood samples were collected before and 5, 10, 20, 40 and 60 min after TRH injection. On the day following blood sampling, all rats were decapitated. The anterior pituitary glands (APs) were excised, and incubated with or without TRH (10 ng/ml) at 37 ° C for 30 min. The basal level of PRL concentration in plasma samples was 5-fold higher in old Ovx rats than in young Ovx rats. Five min after TRH injection, the increase in plasma PRL was greater in old animals than in young animals. Plasma PRL remained higher in old animals than in young animals at 10, 20, 40 and 60 min following TRH challenge. Administration of EB to old and to young Ovx rats produced increases in both basal and TRH-stimulated secretions of PRL, but did not affect the difference in plasma PRL patterns between old and young animals. The release of PRL from APs was increased significantly in all rats after a 30-min incubation with TRH. In Ovx rats injected with oil, the basal release of PRL in vitro was increased with age. The TRH-stimulated release of PRL from APs of oil- and EB-primed rats was also higher in aged rats than in the corresponding young rats. The concentration of plasma TSH in response to TRH was less in old rats than in young rats. Estradiol seemed to have no effect on the secretion of TSH in vivo. Neither aging nor EB injection appeared to alter the spontaneous release of TSH in vitro. However, the release of TSH from APs in vitro in response to TRH was significantly reduced by age. These results suggest that the increased capability of the basal and TRH-stimulated secretion of PRL as well as the decreased capability of the secretion of TSH in response to TRH in old rats was due at least in part to intrinsic changes in anterior pituitary function, including the discordant patterns of lactotrophs and thyrotrophs responding to TRH during the aging process.

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