Yuzuru Kato

Central galanin stimulates pituitary prolactin secretion in rats: Possible involvement of hypothalamic vasoactive intestinal polypeptide

The effect of galanin, a newly identified neuropeptide, on pituitary prolactin (PRL) secretion was examined in the rat. Intracerebroventricular (i.c.v.) injection of all 5 doses of galanin (0.4, 1, 2, 5 and 10 micrograms/rat) raised plasma PRL levels in urethane-anesthetized rats. Galanin injection (2 micrograms/rat, i.c.v.) also increased plasma PRL levels in conscious rats. The intermediate dose of galanin (2 micrograms/rat, i.c.v.) produced a greater response in plasma PRL levels than either smaller or larger doses of galanin. Intravenous injection of galanin did not affect plasma PRL levels. Passive immunization with specific anti-vasoactive intestinal polypeptide (VIP) rabbit serum suppressed plasma PRL response to galanin (2 micrograms/rat, i.c.v.) in anesthetized rats. These findings indicate that central galanin has a stimulatory role in pituitary PRL secretion via the hypothalamus in the rat and that VIP may be involved in rat PRL release induced by galanin.

Galanin stimulates growth hormone (GH) secretion via GH-releasing factor (GRF) in conscious rats

The possibility of a role of hypothalamic growth hormone (GH)-releasing factor (GRF) in GH secretion induced by centrally administered galanin was investigated in freely moving male rats. Intracerebroventricular (i.c.v.) injection of synthetic galanin (0.4 or 2 micrograms/rat) elicited a dose-related increase in plasma GH in these conscious rats. Pretreatment with rabbit antiserum specific for rat GRF significantly inhibited the plasma GH increase induced by i.c.v. injection of galanin (2 micrograms/rat). These findings suggest that galanin-induced GH secretion in the rat is mediated at least in part by hypothalamic GRF.

Nicotine-induced release of noradrenaline from hypothalamic synaptosomes

In order to elucidate the functional role of nicotinic receptors in the hypothalamus, the drug-induced release of noradrenaline from hypothalamic synaptosomes was studied utilizing [3H]noradrenaline ([3H]NA). The release of [3H]NA from synaptosomes was significantly increased with an increase of the dose of nicotine, carbamylcholine chloride, reserpine or tyramine hydrochloride added to the medium, whereas arecoline, atropine sulfate or mecamylamine hydrochloride had no significant effect. Mecamylamine hydrochloride completely inhibited the nicotine- or carbamylcholine-induced release of [3H] at the concentration of 10(-4) M, but had on effect on the reserpine- or tyramine-induced release of [3H]NA. A high concentration of potassium in the medium which depolarizes the synaptosome membrane significantly enhanced the release of [3H]NA. These results strongly suggest that there exist nicotinic cholinergic receptors in brain synaptic regions which play an important role in the function of hypothalamus by releasing noradrenaline and that the release mechanism of noradrenaline induced by nicotine is different from that induced by reserpine and tyramine. Although the existence of postsynaptic nicotinic receptor sites could not be reled out, the present studies indicate the importance of presynaptic cholinergic receptors in the brain.

Effect of β-endorphin on pulsatile luteinizing hormone release in conscious castrated rats

Abstract The effect of intraventricular administration of β-endorphin on pulsatile LH release in castrated conscious rats was studied. The administration of 1 μg of β-endorphin into the lateral ventricle inhibited pulsatile discharge of LH secretion. Intravenous administration of naloxone blocked the suppressive effect of β-endorphin on LH release. These results suggest a possible role of β-endorphin, in addition to Met 5 -enkephalin, in the control of LH release in male rats.

Effects of Neonatal Treatment with Monosodium Glutamate on Growth Hormone Release Induced by Clonidine and Prostaglandin E1 in Conscious Male Rats

Effects of the centrally acting alpha-adrenergic agonist, clonidine, on growth hormone (GH) secretion was studied in conscious male rats pretreated with monosodium glutamate (MSG) during the neonatal period. GH secretory profiles in individual adult rats were obtained by repeated blood samplings every 10-20 min from 10.00 to 17.00 h. GH secretion was pulsatile with mean peak values at around 12.40 and 15.20 h in control rats. When clonidine (15 micrograms/100 g body weight) was injected intravenously into control rats at 14.00 h in the interval between two anticipated spontaneous GH bursts, plasma GH was increased with a mean peak value 20 min after the injection, and the following anticipated spontaneous GH burst was not observed during the experiment. In the rats neonatally treated with MSG (4 mg/g body weight, s.c.), which causes selective destruction of the hypothalamic arcuate nucleus, plasma GH response to clonidine as well as the spontaneous GH bursts were considerably blunted, whereas prostaglandin E1 (5 micrograms/100 g body weight, i.v.) caused an abrupt increase in plasma GH levels in these animals. These results suggest that clonidine stimulates rat GH secretion, possibly by acting within the hypothalamus to stimulate GH releasing factor neurons.

Effects of VIP, TRH, GABA and dopamine on prolactin release from superfused rat anterior pituitary cells

Effects of VIP, TRH, dopamine and GABA on the secretion of prolactin (PRL) from rat pituitary cells were studied in vitro with a sensitive superfusion method. Dispersed anterior pituitary cells were placed on a Sephadex G-25 column and continuously eluted with KRBG buffer. Infusion of TRH (10(-11) - 10(-8)M) and VIP (10(-9) - 10(-6)M) resulted in a dose-related increase in PRL release. LHRH (10(-8) - 10(-5)M) had no effect on PRL release. On the other hand, infusion of dopamine (10(-9) - 10(-6)M) and GABA (10(-8) - 10(-4)M) suppressed not only the basal PRL release from dispersed pituitary cells but also the PRL response to TRH and VIP. The potency of TRH to stimulate PRL release is greater than that of VIP, and the potency of dopamine to inhibit PRL secretion is stronger than that of GABA on a molar basis. These results indicate that TRH and VIP have a stimulating role whereas dopamine and GABA have an inhibitory role in the regulation of PRL secretion at the pituitary level in the rat.

Role of vasoactive intestinal polypeptide (VIP) in regulating the pituitary function in man.

Intramuscular injection of synthetic VIP (200 micrograms) resulted in a rapid increase in plasma prolactin (PRL) concentrations in normal women, which was accompanied by the 4- to 7-fold increase in plasma VIP levels. Mean (+/- SE) peak values of plasma PRL obtained 15 min after the injection of VIP were higher than those of saline control (28.1 +/- 6.7 ng/ml vs. 11.4 +/- 1.6 ng/ml, p less than 0.05). Plasma growth hormone (GH) and cortisol levels were not affected by VIP in normal subjects. VIP injection raised plasma PRL levels (greater than 120% of the basal value) in all of 5 patients with prolactinoma. In 3 of 8 acromegalic patients, plasma GH was increased (greater than 150% of the basal value) by VIP injection. In the in vitro experiments, VIP (10(-8), 10(-7) and 10(-6) M) stimulated PRL release in a dose-related manner from the superfused pituitary adenoma cells obtained from two patients with prolactinoma. VIP-induced GH release from the superfused pituitary adenoma cells was also shown in 5 out of 6 acromegalic patients. VIP concentrations in the CSF were increased in most patients with hyperprolactinemia and a few cases with acromegaly. These findings indicate that VIP may play a role in regulating PRL secretion in man and may affect GH secretion from pituitary adenoma in acromegaly.

Peptide histidine isoleucine- and vasoactive intestinal polypeptide-like immunoreactivity coexist in rat hypophysial portal blood☆

Plasma immunoreactive peptide histidine isoleucine (PHI) and vasoactive intestinal polypeptide (VIP) levels were measured by specific radioimmunoassays in urethane-anesthetized rats. Basal levels of plasma PHI-like immunoreactivity (PHI-LI) in the hypophysial portal blood were 414 +/- 180 pmol/l (means +/- S.E.), about 7 times higher than in the peripheral blood. VIP-like immunoreactivity (VIP-LI) was also high in the portal blood (399 +/- 139 pmol/l). The correlation coefficient between PHI-LI and VIP-LI was 0.76. These findings suggest that PHI and VIP are co-released from the median eminence into the hypophysial portal blood in rats.

Involvement of Alpha-Adrenergic Mechanisms in Growth Hormone Release Induced by Opioid Peptides in Conscious Rats

The effects of synthetic enkephalin analog (KF 33-824) and beta-endorphin on growth hormone (GH) secretion and their interaction with brain monoamines were investigated in unanesthetized male rats. Blood samples (0.4 ml each) were withdrawn every 10-20 min for 6 h from a catheter chronically implanted in the right atrium. In all control rats, immunoreactive GH secretion was pulsatile in nature and two major GH bursts were found to occur around 12.00 and 15.30. The opioid peptides were injected between bursts at 14.00. Following an intravenous administration of FK 33-824 (10 microgram/100 g b.w.), there was an abrupt increase in plasma GH, which was significantly suppressed by naloxone (125 microgram/100 g b.w., i.v.), a specific opiate antagonist. Pretreatment with reserpine (1 mg/100 g b.w., i.p.) abolished not only the natural GH burst but also the GH response to FK 33-824. Pretreatment with dopamine-beta-hydroxylase inhibitors, diethyldithiocarbamate (DDC, 100 mg/100 g b.w., i.v.) and fusarate (10 mg/100 g b.w., i.v.) also inhibited the natural GH burst and GH rise induced by FK 33-824. Intravenous injection of clonidine (15 microgram/100 g b.w.), an alpha-adrenergic stimulant, resulted in an increase in plasma GH in the rats pretreated with reserpine, DDC or fusarate. Phenoxybenzamine (1 mg/100 g b.w., i.v.), an alpha-adrenergic blocking agent, inhibited the GH response to KF 33-824. On the other hand, GH release induced by FK 33-824 was not influenced by propranolol (1 mg/100 g b.w., i.v.), a beta-adrenergic blocking agent, nor pimozide (0.1 mg/100 g b.w., i.v.), a dopamine antagonist. Intraventricular administration of beta-endorphin (5 microgram/rat) also increased the plasma GH levels which were lowered by phenoxybenzamine. These findings suggest that alpha-adrenergic mechanisms are involved in GH release induced by opioid peptides in the rat.

Serotonin stimulates vasoactive intestinal polypeptide release from rat hypothalamus in vitro

Abstract The effect of serotonin (5-HT) on the release of immunoreactive vasoactive intestinal polypeptide (VIP) from rat hypothalamus was examined in vitro with a perifusion system. 5-HT (10 −6 M) and high potassium (56 mM) stimulated VIP release in a calcium-dependent manner. VIP release induced by 5-HT was blunted by cyproheptadine (10 −5 M). These findings suggest that 5-HT has a stimulating effect on VIP release from the hypothalamus.