Role of brain monoamines in release of gonadotropin before proestrus in the cyclic rat.

To determine whether brain monoaminergic neurons are involved in the release of gonadotropins responsible for estrogen increases before proestrus, various inhibitors and precursors of monoamine biosynthesis were administered subcutaneously or intracranially to the 3rd ventricle at 10.00 or 20.00 on the day before proestrus, the 2nd day of diestrus (DII) in 4-day cycling rats. The inhibitors used were alpha-methyl-p-tyrosine (alpha-MPT) and bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)-disulfide (FLA-63). The effects of these drugs on changes in vaginal cytology, ovulation, uterine weight of uterine intraluminal fluid, and on serum concentrations of LH and FSH were evaluated in selected experiments. (1) Administration of alpha-MPT (150 mg/kg s.c.), an inhibitor of tyrosine hydroxylase, at 10.00 on DII reduced weights of uterus and intraluminal fluid on the day of expected proestrus (P), prevented vaginal cornification on estrus (E), blocked ovulation in all 10 rats, and induced prolonged diestrus. (2) Administration of FLA-63 (10 mg/kg s.c.), an inhibitor of dopamine-beta-hydroxylase, at 10.00 on DII reduced weights of uterus and intraluminal fluid on P, blocked ovulation for a few days but did not prevent vaginal cornification at the expected time of E. (3) Administration of alpha-MPT (200 mg/kg) or FLA-63 (15 mg/kg) at 20.00 on DII blocked ovulation in all of 8 and 7 rats, respectively, but these treatments did not block vaginal cornification at the expected time in any animal. (4) Administration of L-DOPA (100 mg/kg) or dihydroxy-phenylserine (DOPS, 200 mg/kg) with alpha-MPT (200 mg/kg) at 20.00 on DII reversed the blocking effect of alpha-MPT on ovulation in 3 out of 6 and 3 out of 5 rats, respectively. (5) Direct application of crystalline alpha-MPT or FLA-63 (about 3-5 mug) to the 3rd ventricle at 20.00 on DII also blocked ovulation in all of 7 and 5 rats, respectively. (6) Both systemic and intraventricular injections of alpha-MPT at 10.00 on DII reduced serum LH on P but not serum FSH. FLA-63 by intraventricular injection also reduced serum LH but not serum FSH. (7) Injection of 17beta-estradiol (40 mug s.c.) with alpha-MPT or FLA-63 partially removed the ovulatory blockade induced by conditions 1, 2, 3 and 5. Therefore, norepinephrine seems to be an important neurotransmitter in the release of gonadotropin responsible for estrogen secretion before P, but dopamine may also be involved during its early stage as represented by 10.00 on DII.