Effect of a Single Intravenous Injection of N‐Methyl‐D,L‐Aspartic Acid on Secretion of Luteinizing Hormone and Growth Hormone in Holstein Bull Calves

Abstract

The role of N-methyl-D-aspartate (NMDA) receptor activation in the central regulation of luteinizing hormone (LH) and growth hormone (GH) was tested by administering a bolus intravenous dose of N-methyl-D,L-aspartic acid (NMA), a NMDA receptor agonist, to 24-week-old intact (n=5), estradiol-treated intact (n=3) and castrated (n=3) Holstein bull calves. The calves were bled for 12h pre- and 100 min post-NMA injection (1.75 mg-/kgBW) periods at 10 min intervals. Concentrations of LH and GH in plasma were measured by specific RIA. Prior to administration of NMA, the average concentration of LH, but not GH, differed significantly among the 3 groups. As expected, administration of estradiol prevented the normal ontogeny of pulsatile LH secretion, while castration resulted in an increased frequency of LH discharges. Injection of NMA resulted in an acute (P<0.001) release of LH in 3 of 5 intact and 3 of 3 estradiol-treated intact calves with the peak response being observed at 20 min (3.18 +/- 1.3 and 5.58 +/- 1.3 ng/ml, respectively) following the challenge. Treatment with NMA did not alter the release of LH in castrate calves. Concentrations of GH in plasma increased (P<0.001) within 20 to 30 min after administration of NMA in intact, estradiol-treated intact and castrate calves with a similar response being observed in each group. Based on these findings, we suggest an involvement of glutamatergic neurotransmission in the hypothalamic or supra-hypothalamic control of LH and GH secretion, and that the excitatory effects of NMDA receptor activation on LH release are overtly influenced by gonadal steroids in bull calves.

Testosterone modulates growth hormone secretion at the hypothalamic but not at the hypophyseal level in the adult male rhesus monkey

“…A similar observation has previously been reported for plasma PRL secretion, demonstrating that in chronically gonadectomized male monkeys testosterone treatment reinstates the PRLreleasing effect of NMA (Arslan et al 1991). It has also been shown that steroid replacement re-establishes the luteinizing hormone response to NMA challenges in some species of mammals (Estienne et al 1990, Shahab et al 1993. Finally, compared with that in normal boys, the GHRH response to -dopa stimulation is less in naturally androgen-deficient individuals with idiopathic delayed puberty (Argente et al 1987, Liapi et al 1988, whereas administration of oxandrolone to these patients significantly increases the -dopa induced GHRH release (Liapi et al 1988).…”

“…administration of the neuroexcitatory amino acid agonist NMA induced a prompt discharge of GH in adult intact male monkeys is not surprising. The ability of NMA to evoke a release of GH has been well documented for rats (Mason et al 1983), pigs (Barb et al 1992), sheep (Estienne et al 1989), holstein bulls (Shahab et al 1993) and monkeys (Plant et al 1989, Medhamurthy et al 1992. The excitatory effects of NMA on GH secretion have been shown to be exerted via the discharge of GHRH from the hypothalamus (Cocilovo et al 1992).…”

Investigation of the serum levels of anterior pituitary hormones in male children with autism

“…There are no available data to interpret this increased GH in basal conditions in autism. However, because the serum levels of glutamate have been shown to be increased in adults with autism [25], and because intravenous administration of excitatory amino acids stimulates GH secretion [26-28], the increased basal GH levels in autism seen in our study may, at least in part, be due to a high concentration of glutamate in the circulation.…”

Presence of vesicular glutamate transporter‐2 in hypophysiotropic somatostatin but not growth hormone‐releasing hormone neurons of the male rat

“…Glutamate is an important regulator of anterior pituitary functions, including regulation of GH synthesis and secretion (Brann, 1995). Subcutaneous N ‐methyl‐DL‐aspartic acid or kainate injections to adult male rats increases serum GH levels (Mason et al ., 1983) and similar stimulatory effects have also been observed in other species (Estienne et al ., 1989; Shahab et al ., 1993). Some of the actions of glutamate on the somatotropic axis may also be exerted at the hypophysial level.…”