Positive role of non-N-methyl-D-aspartate receptors in the control of growth hormone secretion in male rats

Abstract

The role of kainic acid (KA) (an agonist of non-NMDA receptors) in the control of GH secretion and the modulation of KA action by gonadal secretion were analysed in male rats. In the first experiment 4, 8, 12, 16, 20 and 30-day old males were sacrificed 15 min after injecting with vehicle or KA (2.5 mg/kg BW). In the second experiment, the effects of KA, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and MK-801 were analysed in monolayer cultures of dispersed adenohypophyseal cells. In the third experiment, adult males were sham-operated or orchiectomized and decapitated seven days later, 15 min after injecting with vehicle or KA (2.5 or 15 mg/kg BW). In the fourth experiment, males neonatally injected with estradiol benzoate or vehicle were sacrificed on days 45, 60 or 90, 15 min after administration of vehicle or KA (2.5 or 15 mg/kg BW). We found that: (i) KA is a powerful secretagogue for GH in neonatal and postpubertal males but its releasing effectiveness decreases in adulthood; (ii) GH secretion by cultured pituitary cells remains unaffected in the presence of KA (1,10 or 100 mumol/l); (iii) the KA-stimulated GH secretion is increased after orchiectomy and abolished in males neonatally estrogenized. These results indicate that in male rats activation of non-NMDA receptors, probably those located in hypothalamus, increases GH secretion. The releasing properties of KA increases in orchiectomized males and completely disappears in males neonatally estrogenized.

Role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the control of prolactin, growth hormone and gonadotropin secretion in prepubertal rats

“…It is noteworthy that GH responses observed after AMPA administration are not attributable to activation of kainate receptors, as KA was unable to mimic the effects of AMPA on GH secretion in 23-day-old female rats (Table 1). Interestingly, the pattern of GH response to KA administration changes sharply in the immature female rat, with a significant stimulatory effect in 30-day-old females but negligible responses between days 16 and 23 of age (Tena-Sempere et al 1995, Pinilla et al 1996a, and present results). The amplitude of GH response to AMPA was lower in prepubertal females than in males (Fig.…”

“…Activation of AMPA receptors, as was the case for other subtypes of glutamate receptors (Mason et al 1983, Acs et al 1990, Pinilla et al 1996a, Tena-Sempere et al 1995, stimulated GH secretion in prepubertal rats. This fact, together with the decrease in serum GH concentrations observed 60 min after administration of 2·5 mg/kg NBQX, indicate that activation of AMPA receptors takes place as part of the physiological control of GH secretion at this age.…”

“…1), thus pointing to a more relevant role of AMPA receptors in the control of GH secretion in the prepubertal male rat. Such a difference was not observed after administration of NMDA or KA to prepubertal males and females (Pinilla et al 1996a, Tena-Sempere et al 1995. As a whole, these results strongly suggest that the role of different subtypes of EAA receptors in the control of GH secretion in prepubertal rats may be sexually dimorphic, AMPA receptors being more effective in males whereas NMDA and KA receptors were equally potent in both sexes.…”

“…Prepubertal animals were selected for analysis as, at this age, pulsatile secretion of anterior pituitary hormones is not fully established (Gabriel et al 1992, Ojeda & Urbanski 1994, thus allowing a high rate of homogeneity in basal hormone secretion (our personal observations). In addition, solid evidence indicates that the physiological role of several subtypes of glutamate receptors in the control of anterior pituitary secretion is maximally expressed in immature animals, and declines with age (Bourguignon et al 1992, Pinilla et al 1995b, 1996a. Moreover, the crucial role of glutamate receptors subtypes, such as NMDA receptors, in the onset of puberty is well proven (MacDonald & Wilkinson 1990, Urbanski & Ojeda 1990).…”

Gonadal and Age-Related Influences on NMDA-Induced Growth Hormone Secretion in Male Rats

“…The action of EAAs are mediated by different postsynaptic receptors, which include N-methyl- D,L - aspartate (NMDA) receptors, kainate (KA) receptors, 2-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA) receptors, amino-4-phosphobutyric acid (L-AP4) receptors and metabotropic receptors [6]. Previous experiments showed that NMDA and KA given systemically increased GH secretion in prepubertal and adult male rats [7, 8, 9]. The abolition of NMDA effect after destruction of GHRH neurons by neonatal administration of monosodium glutamate (MSG) [8], as well as the reduction in hypothalamic GHRH gene expression after administration of MK-801, an NMDA receptor antagonist [10], have supported the hypothesis that NMDA action is mediated through GHRH neurons [8, 10].…”