The effect of hypothalamic catecholamine synthesis inhibition by alpha-methyltyrosine on gonadotropin secretion during sexual maturation in the male Wistar rat.

Abstract

alpha-Methyl-p-tyrosine (AMPT), a competitive inhibitor of tyrosine hydroxylase, was used to block the synthesis of hypothalamic catecholamines in six different age groups (15, 23, 30, 38, 56, and 72 days of age) in both intact and castrated male rats. Castrated rats received testosterone-filled Silastic capsules of various lengths to give four graded serum concentrations of testosterone in each age group. Intact and castrate animals of all ages were killed 1 week after the castrate group was orchiectomized and outfitted with Silastic capsules. On the day of death, 250 mg/kg BW AMPT base were given ip at zero time, and a second dose (125 mg/kg BW) was given 2 h after the first injection. Rats were killed at zero time and 2 and 4 h after the first AMPT injection. Serum was collected for LH, FSH, and testosterone determinations. AMPT had marked biphasic effects on LH and T secretion, causing both to increase (less than 70% above basal) in the intact immature rats (15 and 23 days of age) and fall (greater than 60% below basal) in the mature rats (38, 56, and 72 days of age). LH increased (up to 307%) in the castrated immature rats in response to AMPT, but no change occurred in the mature castrated rats until moderate concentrations of testosterone were present (1000-2000 pg/ml). Then, LH, as in intact rats, decreased (up to 90%) during exposure to AMPT. These data suggest that the ratio of stimulatory and inhibitory effects of hypothalamic norepinephrine and dopamine changes during sexual maturation, with inhibitory effects predominating in the prepubertal rat.