Intraventricular administration of estradiol modulates rat prolactin secretion and synthesis

The effect of estradiol (E2) on rat tuberoinfundibular dopaminergic (TIDA) neurons was examined in vivo, employing chronic intraventricular (i.c.v.) infusion technique using an osmotic mini-pump. The activity of TIDA neurons was assessed by the release and synthesis of prolactin (PRL) in the rat pituitary gland and by the changes in the 3, 4-dihydroxyphenylacetic acid (DOPAC) and dopamine (DA) levels and in the DOPAC/DA ratio in the rat hypothalamus. We also examined the [3H] E2 binding in the rat hypothalamus. Ovariectomized female Wistar rats with E2 replacement were treated with daily i.c.v. infusion of 1 microM of E2 or saline vehicle for 1, 3, and 7 days using the Alzet osmotic mini-pump and brain infusion kit. At 1 day of i.c.v. infusion of E2, the serum PRL level was significantly decreased compared with that in the vehicle group. Northern blot analysis of the total RNA isolated from the pituitary glands demonstrated a decrease in the PRL gene transcript level in the E2 group. At 3 days of E2 treatment, however, the serum PRL level was significantly increased compared with that of the vehicle-injected group and Northern blot analysis also demonstrated that the PRL gene transcript level was increased in the E2 group. At 7 days of E2 administration, there were no significant differences between the E2 and vehicle groups in either serum PRL or PRL gene transcript levels. There was a significant increase in the DOPAC/DA ratio after 1 day in the E2 group. However, no significant effects of E2 on this ratio were observed at 3 and 7 days of treatment. The DOPAC concentration in the E2 group was significantly increased at day 1 and significantly decreased at day 3, compared with that of the respective time in vehicle group. At day 7 there was no significant change in DOPAC concentration in either groups. The DA concentrations in the hypothalamus was not changed on any day in either group. Specific [3H] E2 binding was observed in the rat hypothalamus. These data suggest that E2 may have a biphasic effect on the accumulation of PRL gene transcripts and on the PRL secretion in the rat pituitary by first stimulating and then inhibiting the TIDA neuronal activity.