Summary
Although the presence of ionotropic (iGluRs) and metabotropic (mGluRs) glutamate receptors
has been demonstrated in the anterior pituitary, recent reports on the direct effect
of glutamate on prolactin (PRL) secretion by anterior pituitary cells have presented
contradictory results. Hence, the aim of this study was to determine the effect of
ionotropic (iGluRs) and metabotropic (mGluRs) glutamate receptor agonists on prolactin
(PRL) release. In addition, since D-Aspartate (D-Asp) is found in the pituitary and
is involved in neuroendocrine regulation, we also studied the direct action of D-Asp
on PRL secretion. Finally, since the posterior pituitary participates in the regulation
of PRL secretion, we examined the influence of the posterior pituitary on the effects
of NMDA and D-Asp on PRL release. - Glutamate (1000 μM) increased PRL secretion from
cultured anterior pituitary cells. Both NMDA (100 μM) and kainate (100 μM) increased
PRL secretion and these effects were blocked by a specific NMDA receptor antagonist.
AMPA did not modify PRL release in these cultures. The group I and II mGluR agonist,
trans-ACPD (1000 μM), and a specific group II mGluR agonist, L-CCG-I (100-1000 μM),
inhibited whereas specific group I and III mGluR agonists, 3-HPG and L-AP4 respectively,
had no effect on PRL release. Finally, D-Asp (100-1000 μM) stimulated PRL secretion
and this effect was reduced by a NMDA receptor antagonist. When anterior pituitary
cells were cultured in the presence of posterior pituitary cells, NMDA did not modify
PRL or GABA release, while D-Asp increased PRL secretion and decreased GABA release
in these cocultures. - In conclusion, our results show that L-glutamate has a differential
direct effect on PRL release: it exerts a stimulatory action via iGluRs and an inhibitory
effect via mGluRs. D-Asp could directly stimulate PRL release through NMDA receptors.
D-Asp may also stimulate PRL release by decreasing GABA release from the posterior
pituitary.
Key words:
Pituitary - Glutamate - Ionotropic receptors - Metabotropic receptors - D-aspartate
- Prolactin
References
- 1
Aguilar E, Tena-Sempere M, Aguilar R, González D, Pinilla L.
Interactions between N-methyl-D-aspartate, nitric oxide and serotonin in the control of prolactin secretion
in prepubertal male rats.
Eur J Endocrinology.
1997;
137
99-106
- 2
Bernasconi R, Bittiger H, Heid J, Martin P.
Determination of GABA levels by a 3H-muscimol-radioreceptor assay.
J Neurochem.
1980;
34
614-618
- 3
Brann D W, Mahesh V B.
Endogenous excitatory amino acid involvement in the preovulatory and steroid-induced
surge of gonadotropins in the female rat.
Endocrinology.
1991;
128
1541-1547
- 4
Brann D W, Mahesh V B.
Excitatory amino acids: evidence for a role in the control of reproduction and anterior
pituitary hormone secretion.
Endocrine Rev.
1997;
18
678-700
- 5
Brann D W, Ping L, Mahesh V B.
Possible role of non-NMDA receptor-mediated neurotransmission in steroid-induced and
preovulatory gonadotropin surges in the rat.
Mol Cell Neurosci.
1993;
4
292-297
- 6
Conn J P, Pin J P.
Pharmacology and functions of metabotropic glutamate receptors.
Annu Rev Pharmacol Toxicol.
1997;
37
205-237
- 7
Costa A, Yasin S A, Hucks D, Forsling M L, Besser G M, Grossman A.
Differential effects of neuroexcitatory amino acids on corticotropin-releasing hormone-41
and vasopressin release from rat hypothalamic explants.
Endocrinology.
1992;
131
2595-2602
- 8
D'Aniello A, Di Fiore M M, Fisher G H, Milone A, Seleni A, D'Aniello S, Perna A F,
Ingrosso D.
Occurrence of D-aspartic acid and N-methyl-D-aspartic acid in rat neuroendocrine tissues and their role in the modulation
of luteinizing homone and growth hormone release.
FASEB J.
2000a;
14
699-714
- 9
D'Aniello G, Tolino A, D'Aniello A, Errico F, Fisher G H, Di Fiore M M.
The role of D-aspartic acid and N-methyl-D-aspartic acid in the regulation of prolactin release.
Endocrinology.
2000b;
141
3862-3870
- 10
De Laurentiis A, Pisera D, Duvilanski B, Rettori V, Lasaga M, Seilicovich A.
Neurokinin A inhibits oxytocin and GABA release from the posterior pituitary by stimulating
nitric oxide synthase.
Brain Res Bul.
2000;
53
325-330
- 11
Dymshitz J, Ben-Jonathan N.
Coculture of anterior and posterior pituitary cells: selective stimulation of lactotrophs.
Endocrinology.
1991;
128
469-2475
- 12
Ferrari M D, Odink J, Bos K D, Malessey M JA, Bruyn G W.
Neuroexcitatory plasma amino acids are elevated in migraine.
Neurology.
1990;
40
1582-1586
- 13
Frawley L S.
Role of the hypophyseal neurointermediate lobe in the dynamic release of prolactin.
Trends Endocrinol Metab.
1994;
5
107-112
- 14
Gay V L, Plant T M.
N-methyl-D,L-aspartate elicits hypothalamic gonadotropin-releasing hormone release
in prepubertal male rhesus monkeys.
Endocrinology.
1987;
120
2289-2296
- 15
Gonzalez L C, Pinilla L, Tena-Sempere M, Aguilar E.
Role of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors in the control
of prolactin, growth hormone and gonadotropin secretion in prepubertal rats.
J Endocrinol.
1999;
162
417-424
- 16
Hashimoto A, Oka T.
Free D-aspartate and D-serine in the mammalian brain and periphery.
Prog Neurobiol.
1997;
52
325-353
- 17
Henley J M, Ambrosini A, Rodriguez-Ithurralde D, Sudan H, Brackley P, Kerry C, Mellor I,
Abutidze K, Usherwood P NR, Barnard E A.
Purified unitary kainate/α-amino-3-hydroxy-5-methylisooxazole-propionate (AMPA) and
kainate/AMPA/N-methyl-D-aspartate receptors with interchangeable subunits.
Proc Natl Acad Sci USA.
1992;
89
4806-4810
- 18 Kordon C, Drouva S V, Martinez de la Escalera G, Weiner R I. Role of classic and
peptide neuromediators in the neuroendocrine regulation of luteinizing hormone and
prolactin. In: Knobil E, Neill JD (eds) The physiology of Reproduction, Second Edition
Raven Press, New York 1994: 1621-1682
- 19
Lasaga M, De Laurentiis A, Pampillo M, Pisera D, Díaz M, Theas S, Duvilanski B, Seilicovich A.
The effect of excitatory aminoacids on GABA release from mediobasal hypothalamus of
female rats.
Neurosci Lett.
1998;
247
119-122
- 20
Laudon M, Grossman D A, Ben-Jonathan N.
Prolactin-releasing factor: cellular origin in the intermediate lobe of the pituitary.
Endocrinology.
1990;
126
3185-3192
- 21
Lee J, Homma H, Tashiro K, Iwatsubo T, Imai K.
D-aspartate localization in the rat pituitary gland and retina.
Brain Res.
1999;
838
193-199
- 22
Login I S.
Direct stimulation of pituitary prolactin release by glutamate.
Life Sci.
1990;
47
2269-2275
- 23
Meeker R B, Greenwood R S, Hayward J N.
Glutamate receptors in the rat hypothalamus and pituitary.
Endocrinology.
1994;
134
621-629
- 24
Meldrum B S.
Glutamate as a neurotransmitter in the brain: review of physiology and pathology.
J Nutr.
2000;
130
1007S-15S
- 25 Neill J D, Nagy G M. Prolactin secretion and its control. In: Knobil E, Neill JD
(eds) The physiology of Reproduction, Second Edition. Raven Press, New York 1994:
1833-1860
- 26
Niimi M, Sato M, Murao K, Takahara J, Kawanishi K.
Effect of excitatory amino acid receptor agonists on secretion of growth hormone as
assessed by the reverse hemolytic plaque assay.
Neuroendocrinology.
1994;
60
173-178
- 27
O'Conner J L, Wade M F.
Evidence that the posterior pituitary plays a role in neuropeptide Y and luteinizing
hormone-releasing hormone-stimulated gonadotropin secretion in vitro.
Proc Soc Exp Biol Med.
1996;
213
59-64
- 28
Pampillo M, De Laurentiis A, Duvilanski B, Pisera D, Díaz M C, Seilicovich A, Lasaga M.
NMDA receptor-mediated control of GABA release from neurointermediate lobes of female
and male rats.
Brain Res.
1999;
842
469-472
- 29
Parker S L, Crowley W R.
Stimulation of oxytocin release in the lactating rat by central excitatory amino acid
mechanisms: evidence for specific involvement of R,S-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-sensitive glutamate receptors.
Endocrinology.
1993;
133
2847-2854
- 30
Perry T L, Krieger C, Hansen S, Eisen A.
Amyotrophic lateral sclerosis: amino acid levels in plasma and cerebrospinal fluid.
Ann Neurol.
1990;
28
12-17
- 31
Petralia R S, Wang Y X, Niedzielski A S, Wenthold R J.
The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic,
presynaptic and glial localizations.
Neuroscience.
1996;
71
949-976
- 32
Pinilla L, González D, Tena-Sempere M, Aguilar R, Aguilar E.
Mechanisms of inhibitory action of kainic acid on prolactin secretion in male rats.
J Endocrinol.
1996;
151
159-167
- 33
Pohl C R, Lee L R, Smith M S.
Qualitative changes in luteinizing hormone and prolactin responses to N-methyl-aspartic acid during lactation in the rat.
Endocrinology.
1989;
124
1905-1911
- 34
Schell M J, Cooper O B, Snyder S H.
D-aspartate localizations imply neuronal and neuroendocrine roles.
Proc Natl Acad Sci USA.
1997;
94
2013-2018
- 35
Strobl F J, Luderer U, Besecke L, Wolfe A, Schwartz N B, Levine J E.
Differential gonadotropin responses to N-methyl-D,L-aspartate in intact and castrated male rats.
Biol Reprod.
1993;
48
867-873
- 36
Wilson R C, Knobil E.
Acute effects of N-methyl-D,L-aspartate on the release of pituitary gonadotropins and prolactin in the
female rhesus monkey.
Brain Res.
1982;
248
177-179
- 37
Zanisi M, Galbiati M, Messi E, Martini L.
The anterior pituitary gland as a possible site of action of kainic acid.
Proc Soc Exp Biol Med.
1994;
206
431-437
Mercedes Lasaga
Centro de Investigaciones en Reproducción
Facultad de Medicina
Piso 10
Buenos Aires (1121)
Argentina
Phone: +54-11-5950-9612
Fax: +54-11-4807-4052
Email: mlasaga@fmed.uba.ar