The role of excitatory amino acid pathways in the control of pituitary function in neonatally oestrogenized male rats

Abstract

Abstract It is well known that in the rat neonatal manipulation of the sex steroid environment results in altered hypothalamic-pituitary function in adulthood which implies an abnormal prolactin secretion and gonadotrophin response to orchidectomy. The present paper analyses the involvement of excitatory amino acid pathways in the disturbed gonadotrophin and prolactin secretion in male rats neonatally injected with oestradiol benzoate (500 μg on the day of birth). In the first experiment, 60-day-old control and oestrogenized male rats (intact or orchidectomized a week before) were killed 15 min after injection of vehicle, N-methyl-d-aspartic acid (NMDA; 15 mg/kg) or kainic acid (KA; 15 mg/kg). In the second experiment, prepubertal males were killed 15 min after injection of vehicle or NMDA. In the third experiment 30-, 45-, 60-and 90-day-old intact control and oestrogenized males were killed 15 min after injection of vehicle or KA. In the fourth experiment, control and oestrogenized males were sham-orchidectomized, orchidectomized or orchidectomized and implanted with Silastic capsules at 30 days of age and killed on day 90, 15 min after vehicle or KA injection. We found that (1) as previously reported, oestrogenized males showed hyperprolactinaemia and absence of LH and FSH responses after orchidectomy, (2) the stimulatory effect of NMDA on LH secretion was observed in prepubertal control and in prepubertal and adult oestrogenized males, (3) KA stimulated LH secretion only in prepubertal (30-day-old) and peripubertal (45-day-old) control males, whereas stimulation was observed in oestrogenized males at all ages studied, except when they were implanted with testosterone, (4) FSH secretion was only stimulated in oestrogenized orchidectomized males, and (5) prolactin secretion was inhibited by NMDA and KA in control and oestrogenized males. The greater effectiveness of NMDA and KA on gonadotrophin secretion in oestrogenized males, a finding especially noticeable after orchidectomy, may reflect the existence of a greater pool of releasable GnRH, a consequence of the absence of response to orchidectomy. The decrease in prolactin secretion after NMDA or KA administration in oestrogenized males may be mediated by an increase in dopaminergic tone, presumably reduced in the hyperprolactinaemic oestrogenized males. Finally, the effectiveness of KA on prolactin and LH secretion was maintained in adult oestrogenized males, perhaps because of the permanent decrease in testosterone secretion. Journal of Endocrinology (1995) 147, 51–57