Hypothalamic versus pituitary stimulation of luteinizing hormone secretion in the prepubertal female lamb

Glutamate and aspartate have been hypothesized to function as neurotransmitters in the regulation of the gonadotropin-releasing hormone (GnRH) neurosecretory system. We, therefore, determined if hypothalamic stimulation of luteinizing hormone (LH) secretion in the intact prepubertal female lamb could be achieved by intravenous injection of N-methyl-D,L-aspartate (NMA), a glutamate agonist. A pilot study determined a dose of NMA that would induce physiologic pulses of LH (GnRH). Subsequently, we compared the ability of NMA with exogenous GnRH to induce ovulation in the prepubertal lamb when administered chronically. Eighteen prepubertal lambs (21 weeks of age, 34.2 +/- 1.5 kg body weight) were treated intravenously with either NMA (2 mg/kg, n = 6) or GnRH (68 ng/injection or approximately 2 ng/kg, n = 6) for 3 days, every 2 h on day 1 and every 1 h on days 2 and 3, or received no treatment (controls, n = 6). Gonadotropin surges were detected only in GnRH-treated lambs (5/6 lambs, onset = 54.0 +/- 4.5 h from the start of study, mean +/- SE). Compared to 83% of GnRH injections inducing LH pulses, only 47% of NMA injections induced LH pulses. Because each injection of NMA did not induce a pulse of LH, a second experiment was performed in an attempt to optimize the LH response to NMA. Ten prepubertal lambs (25 weeks of age) were injected every 2 h for 24 h with higher doses of NMA, either 4 mg/kg (n = 5) or 16 mg/kg (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)