Tatsuhide Inoue

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.

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.

Inhibition by antiserum to Vasoactive Intestinal Polypeptide (VIP) of prolactin secretion induced by serotonin in the rat

Intraventricular (i.c.v.) injection of serotonin (5HT) or intravenous (i.v.) injection of 5-hydroxytryptophan (5HTP), a precursor of 5HT, raised plasma prolactin (PRL) levels in urethane-anesthetized rats pretreated with normal rabbit serum. When the animals were injected i.c.v. or i.v. with specific anti-VIP rabbit serum, the plasma PRL responses to 5HT and 5HTP were blunted. These findings suggest that hypothalamic VIP is involved, at least in part, in PRL secretion induced by central serotonergic stimulation in the rat.

Further evidence that peptide histidine isoleucine (PHI) may function as a prolactin releasing factor in rats

Intraventricular administration of peptide histidine isoleucine (PHI) (200 ng, 1, 5 and 10 micrograms/rat) resulted in a significant and dose-related increase in plasma prolactin (PRL) levels in urethane-anesthetized rats and in conscious rats with intraatrial and intraventricular catheters. Intravenous injection of PHI (10 micrograms/rat) also raised plasma PRL levels in these animals. In in vitro studies, PRL release from superfused rat anterior pituitary cells was stimulated by PHI (10(-9), 10(-8) and 10(-7) M) in a dose-related manner. The stimulating effect of PHI (10(-7)M) on PRL release in vitro was as potent as that of vasoactive intestinal polypeptide (VIP) (10(-7) M) and was observed even in the presence of dopamine (10(-7) M). These results suggest that PHI plays a stimulating role in regulating PRL secretion by acting, at least in part, directly on the pituitary in the rat.

Galanin stimulates the release of vasoactive intestinal polypeptide from perifused hypothalamic fragments in vitro and from periventricular structures into the cerebrospinal fluid in vivo in the rat

Intracerebroventricular injection of galanin (2 micrograms/rat) raised plasma prolactin (PRL) levels in the rat, which was accompanied by an increase in immunoreactive vasoactive intestinal polypeptide (VIP) in the cerebrospinal fluid (CSF). Immunoreactive VIP release from superfused rat hypothalamic fragments in vitro was dose-relatedly stimulated by galanin (10(-7) and 10(-8) M). PRL release from superfused rat anterior pituitary cells was stimulated by TRH (10(-8) M) but not affected by galanin (10(-7) to 10(-5) M). These findings indicate that central galanin has a stimulating role in the release of hypothalamic VIP, which results in pituitary PRL secretion in the rat.

Involvement of Hypothalamic Vasoactive Intestinal Polypeptide (VIP) in Prolactin Secretion Induced by Serotonin in Rats

Abstract To study the possible involvement of hypothalamic vasoactive intestinal polypeptide (VIP) in regulating the secretion of prolactin (PRL), the effect of anti-VIP rabbit serum on serotonin (5-HT)-induced PRL release was examined in urethane-anesthetized male rats. Anti-VIP serum (AVS) or normal rabbit serum (NRS) was infused into a single hypophysial portal vessel of the rat for 40 min at a rate of 2 μl/min with the aid of a fine glass cannula and 5-HT was injected into a lateral ventricle 10 min after the start of the infusion. Intraventricular injection of 5-HT (10 μg/rat) caused an increase in plasma PRL levels in control animals infused with NRS and 5-HT-induced PRL release was blunted in animals infused with AVS (mean±SE peak plasma PRL: 118.9±19.8 ng/ml vs 54.7±16.2 ng/ml, p<0.05). These findings suggest that the secretion of PRL induced by 5-HT is mediated, at least in part, by hypothalamic VIP release into the hypophysial portal blood in the rat.

Inhibition by Antiserum to Rat Growth Hormone-Releasing Factor of Growth Hormone Secretion Induced by A Met5-Enkephalin Analog, FK33-824, in Rats

Abstract A Met5-enkephalin analog, FK33-824 (5, 10 and 20 ug/100 g body wt, iv) caused a dose-related increase in plasma growth hormone (GH) in urethane-anesthetized male rats. Pretreatmentwith cysteamine (30 mg/100 g body wt, sc), a depletor of hypothalamic somatostatin, increased the plasma GH response to FK33-824 (10 ug/100 g body wt, iv). Antiserum specific for rat GH-releasing factor (GRF)(0.5 ml/rat, iv) blunted GH release induced by FK33-824 (10 ug/100 g body wt, iv) in rats with or without cysteamine pretreatment. These results suggest that GH secretion induced by the opioid peptide is mediated, at least in part, by hypothalamic GRF in the rat.

Interaction between vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in stimulating the secretion of prolactin from rat anterior pituitary cells in vitro

Interaction between vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in regulating the secretion of prolactin (PRL) from the pituitary was investigated in the rat in vitro using two different methods: (1) short incubation of anterior pituitary cells and (2) superfusion of the pituitary cell column. PRL levels in the incubation medium were raised by addition of either VIP or PHI in concentrations of 10(-9) M to 10(-7) M in a dose-related manner. When both peptides were simultaneously added, additive stimulating effect on PRL release was obtained below the VIP concentration of 10(-7) M, in which no additive effect of PHI was revealed. PRL release from superfused rat pituitary cells was stimulated by 5-min pulses of VIP (10(-7) M), PHI (10(-7) M) and TRH (10(-8) M). Infusion of VIP for 200 min in the concentration of 0.3 x 10(-7) M resulted in an increase in basal release of PRL and blunted PRL release induced by not only VIP but also PHI stimulation, whereas PRL release induced by TRH was not affected. Infusion of PHI (0.3 x 10(-7) M, 0.7 x 10(-7) M and 10(-7) M) for 200 min also dose-relatedly suppressed PRL release induced by not only PHI but also VIP without any change in PRL release induced by TRH. These findings suggest that VIP and PHI may act through a common binding site on the pituitary lactotroph in the rat.

Stimulation of prolactin secretion by L-3,4-dihydroxyphenyl-serine (L-dops) via central norepinephrine in the rat

Intracerebroventricular (icv) injection of L-3,4-dihydroxyphenylserine (L-DOPS) (50 and 250 micrograms/rat) raised in a dose-related manner both plasma prolactin (PRL) and CSF norepinephrine (NE) in urethane-anesthetized male rats. Intravenous (iv) injection of larger doses of L-DOPS (5 and 10 mg/100 g BW) slightly but significantly increased plasma PRL and CSF NE. L-DOPS injection (50 micrograms/rat, icv or 5 mg/100 g BW, iv) also raised plasma PRL in conscious rats. There was a good correlation (r = 0.74) between CSF NE and peak plasma PRL in the anesthetized animals. Propranolol (100 micrograms/100 g BW, iv) inhibited plasma PRL responses to L-DOPS (50 micrograms/rat, icv) and NE injection (1 microgram/rat, icv) raised plasma PRL in anesthetized animals. These findings indicate that L-DOPS stimulates PRL secretion via central noradrenergic mechanisms in the rat.