Introduction Different factors are involved in the decline of the reproductive system with age. A decrease in ovarian function, as indicated by a reduced number of ovarian follicles and an associated increase in ovarian resistance to gonadotrophins, has been reported (Navot et al., 1994; Hofmann et al., 1995). The role of the hypothalamo–pituitary axis during the decline of reproductive function remains uncertain. Attenuated preovulatory LH surges related to a decrease in LH pulse amplitude with no change in pulse frequency have been found in female rats during reproductive ageing. This finding indicates that a deficient GnRH drive or reduced responsiveness to the GnRH signal, rather than altered timing of the signal, accounts for the age- related decline in reproductive function as reflected by an attenuated pro-oestrous LH surge in middle-aged rats (Matt et al., 1998). Studies in young and middle-aged female rats have indicated that reduced pituitary responsiveness to GnRH may contribute to the delayed and attenuated pro- oestrous LH surge that precedes reproductive senescence (Smith et al., 1982). Brito et al. (1994) concluded that a decrease in pituitary LH responsiveness to GnRH is only apparent in middle-aged rats that display attenuated pro- oestrous LH surges. Ageing of the female reproductive system in rats is marked by discrete stages in the disappearance of regular oestrous cyclicity. Transition to acyclicity is characterized by increased LH pulse duration but decreased amplitude. Changes in pulse generator function may play a role in the age-related transition to acyclicity (Scarbrough and Wise, 1990). Melatonin has been found to inhibit ageing processes (Pierpaoli et al., 1997; Oaknin-Bendahan et al., 1995; Rasmussen et al., 1999) and its secretion is reduced in senescence (Waldhauser and Steger, 1986; Reiter, 1992). Evidence of hypothalamic melatonin receptor sites (Zisapel et al., 1987) and changes consistent with inhibition of GnRH release after hypothalamic melatonin implants (Glass and Knotts, 1987) have led to the hypothesis that melatonin modulates GnRH Journal of Reproduction and Fertility (2000) 119, 151–156 Effects of ageing and exogenous melatonin on pituitary responsiveness to GnRH in rats E. Diaz 1 , D. Pazo 2 , A. I. Esquifino 2 and B. Diaz 1 1 Dpto Biología Funcional. Area Fisiología, Fac. Medicina, Universidad de Oviedo, Oviedo; and 2 Dpto Bioquímica y Biología Molecular III, Fac. Medicina, Universidad Complutense, Madrid, Spain The effect of age and melatonin on the activity of the neuroendocrine reproductive system was studied in young cyclic (3–5 months-old), and old acyclic (23–25 month- old) female rats. Pituitary responsiveness to a bolus of GnRH (50 ng per 100 g body weight) was assessed at both reproductive stages in control and melatonin-treated (150 μg melatonin per 100 g body weight each day for 1 month) groups. After this experiment, female rats were treated for another month to study the influence of ageing and melatonin on the reproductive axis. Plasma LH, FSH, prolactin, oestradiol and progesterone were measured. A positive LH response to GnRH was observed in both control groups (cyclic and acyclic). However, a response of greater magnitude was observed in old acyclic rats. Melatonin treatment reduced this increased response in acyclic rats and produced a pituitary responsiveness similar to that of young cyclic rats. FSH secretion was independent of GnRH administration in all groups, indicating desynchronization between LH and FSH secretion in response to GnRH in young animals and during senescence. No effect on prolactin was observed. Significantly higher LH (3009.11  1275.08 pg ml –1 ; P < 0.05) and FSH concentrations (5879.28  1631.68 pg ml –1 ; P< 0.01) were seen in acyclic control rats. After melatonin treatment, LH (811.11  89.71 pg ml –1 ) and FSH concentrations (2070  301.62 pg ml –1 ) decreased to amounts similar to those observed in young cyclic rats. However, plasma concentrations of oestradiol and progesterone were not reduced. In conclusion, the results of the present study indicate that, during ageing, the effect of melatonin is exerted primarily at the hypothalamo–pituitary axis rather than on the ovary. Melatonin restored the basal concentrations of pituitary hormones and pituitary responsiveness to similar values to those observed in young rats. © 2000 Journals of Reproduction and Fertility Ltd 0022–4251/2000 Received 1 September 1999. Downloaded from Bioscientifica.com at 01/03/2019 03:43:48AM via free access