Effect of hypothalamic surgery on prolactin release induced by 5-hydroxytryptophan (5-HTP) in rats.

Intravenous injections of varying doses of 5-HTP (1, 3 and 5 mg/100 g body wt), a precursor of serotonin, caused a significant and dose-related increase in plasma prolactin concentrations in urethane-anesthetized rats. Increases in plasma prolactin concentrations caused by 5-HTP (1 mg/100 g body wt iv) were abolished by the concomitant administration of L-DOPA (2 mg/100 g body wt iv). Plasma prolactin levels were also significantly elevated following the injection of 5-HTP in rats with complete hypothalamic deafferentation, whereas 5-HTP had no significant effect on plasma prolactin levels in rats with extensive hypothalamic ablation. These results suggest that 5-HTP causes prolactin secretion by stimulating the serotoninergic mechanism in the hypothalamus.     

Responses of MSH and prolactin cells to 5-hydroxytryptophan (5-HTP) in amphibians and teleosts

Summary Injection of 5-hydroxytryptophan (5-HTP), a precursor of serotonin, induces dispersion of melanin in the amphibians, Pleurodeles waltlii (Urodela) and Xenopus laevis (Anura), in the goldfish, Carassius auratus, and in the carp, Cyprinus carpio. It is accompanied by a dispersion of erythrophore pigments. In the pituitaries of Pleurodeles and goldfish, a stimulation of MSH cells, characterized by a significant nuclear hypertrophy, is also observed; in Carassius, MSH cells may become degranulated. Serotonin appears to exert a stimulating effect on MSH release in lower vertebrates. Swimming behavior is disturbed in the goldfish and the carp; gaseous metabolism in the swim-bladder may be affected by injection of 5-HTP, as previously reported in the eel. Prolactin (PRL) cells appear activated, but remain granulated in the treated goldfish. No clear response of PRL cells to injection of 5-HTP can be observed in Pleurodeles. A possible role of serotonin in Pleurodeles submitted to an experimental aeroionization is briefly discussed.     

Effect of adrenalectomy and 5-hydroxytryptophan on phasic release of luteinizing hormone

The effect of 5-hydroxytryptophan (5-HTP) on serum progesterone and the possible role of adrenal progesterone in mediating stimulation by 5-HTP of phasic release of luteinizing. hormone (LH) were investigated in estradiol benzoate (EB)-treated ovariectomized rats. LH surges were induced in long-term (at least two weeks) ovariectomized rats by two injections of EB (20 micrograms/rat, s.c.) with an interval of 72 hrs. Administration of 5-HTP (50 mg/kg, i.p.) at 1000 hr in EB-treated ovariectomized rats resulted in a four-fold increase in serum progesterone within 30 mins, and significantly stimulated the LH surge at 1600 hr. This facilitative effect of 5-HTP on serum LH, but not progesterone, was further potentiated in rats pretreated with P-chlorophenylalanine (PCPA) 72 hrs earlier. Adrenalectomy shortly before 5-HTP administration attenuated the LH surge in saline treated controls, and completely blocked the facilitative effect of 5-HTP on the afternoon surge of LH in rats pretreated with PCPA 72 hrs earlier. On the other hand, chronic adrenalectomy (for 6 days) followed by hydrocortisone (0.2 mg/rat/day) replacement not only had no effect on the LH surge in saline treated controls, but also failed to prevent 5-HTP from facilitating the LH surge in PCPA pretreated rats. On the first day of bleeding, the basal LH value at 1000 hr in sham operated controls was significantly suppressed by PCPA pretreatment 48 hrs earlier. The second dose of 5-HTP administered on the next day failed to potentiate LH surges in either sham operated or adrenalectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of prolactin release by angiotensin

In superfused anterior pituitary cell aggregates, prolactin release is stimulated by angiotensin II (AII) in a concentration-dependent fashion between 0.1 and 10 nM. When studied in aggregates prepared from pituitary cell populations separated according to size by unit gravity sedimentation, the PRL response to AII was weak in a population enriched in lactotrophs but deprived of gonadotrophs. In other separated populations, the response increased with the proportional number of gonadotrophs. The response also increased when lactotrophs were co-aggregated with an enriched population of gonadotrophs. It is proposed that the PRL response to AII is augmented by an intercellular messenger system presumably operating between gonadotrophs and lactotrophs.     

Antagonism of estrogen-induced prolactin release by dihydrotestosterone

Previous work from our laboratory has demonstrated that progesterone can inhibit estrogen-induced prolactin release in female rats. Since androgens have been reported to mimic progesterone actions in certain systems, and to antagonize estrogen action in rat uteri, the purpose of this study was to determine whether androgens, like progestins, can inhibit estrogen-induced prolactin release. The ovariectomized (26 days of age) immature rat was used as the model for analysis of this question. Dihydrotestosterone (DHT) was chosen to be used throughout the study since it does not undergo aromatization to estrogens. In response to estradiol exposure (2 micrograms/rat), prolactin release reached peak values at 12 h and returned to control levels by 24 h. A second injection of estradiol 13 h after its initial injection stimulated a second increase in serum prolactin at 25 h. A single injection of DHT (0.8 mg/kg BW) 1 h before the second estradiol injection blocked the increase in serum prolactin. DHT had no effect on basal serum prolactin levels. The DHT inhibition of estrogen-induced prolactin release required estrogen priming. A dose dependency for the DHT effect was demonstrated, with low doses effective and high doses ineffective, in inhibiting estrogen action. This effect of DHT seemed to be androgen receptor-mediated, since flutamide blocked the effect. However, the possibility of progestin receptor mediation could not be ruled out since RU486 also blocked DHT's effect. Flutamide was also effective in blocking progesterone's inhibition of estrogen-induced action. This is perhaps consistent with an overlap of activities in androgens and progestins reported by several investigators.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antagonism of estrogen-induced prolactin release by progesterone

Previous work from our laboratory has shown that during the process of nuclear occupancy of the progesterone receptor complex (1-2 h), nuclear estradiol receptors of the anterior pituitary are depleted. The purpose of this study was to determine whether the depletion of nuclear estradiol receptors by progesterone had functional biological significance. The ovariectomized (26 days of age) immature rat was used as the model for analysis of this question. The ability of estradiol to release prolactin from the anterior pituitary was the function chosen to determine the biological significance of the progesterone and estradiol interactions. In response to estradiol exposure (2 micrograms/rat), prolactin release reached peak values from 8 h to 12 h and returned to control levels by 24 h. A second injection of estradiol 13 h after the initial injection stimulated a second increase in serum prolactin at 25 h. This model of two injections of estradiol 13 h apart served to provide adequate levels of anterior pituitary progesterone receptors and elevated serum prolactin levels upon which superimposed progestin modulation could be examined. A single injection of progesterone (0.8 mg/kg BW) 1 h before the second estradiol injection blocked the increase in serum prolactin. This action was a receptor-mediated event because progesterone had no effect without estrogen priming or when the progesterone antagonist RU486 was used. Finally, when the interval between the progesterone and second estradiol injection was extended to 4 h, a time period when progesterone does not deplete pituitary nuclear estrogen receptors, the estrogen-induced increase in serum prolactin was not blocked.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enkephalin-stimulated prolactin release

The effect of methionine- and leucine-enkephalina^a on prolactin secretion was studied in vivo and in vitro. Administration of methionine-enkephalin to rats (5 mg/kg) resulted in a consistent increase in plasma prolactin. In monolayer cultures of rat pituitaries both enkephalins released prolactin at concentrations as low as 5 ng/ml.     

Induction of prolactin release by LRF and LRF-agonist

Infusion of LRF (0.2 μg/min × 3.5 hrs) and injection of LRF-agonist (50 μg, SC) elicited a prompt and sustained PRL release by the pituitary. This effect is independent of ovarian steroid environment as observed in both normal cycling women and hypogonadal subjects with similar time course and magnitude of PRL release.     

Direct stimulation of pituitary prolactin release by glutamate

The ability of glutamate and other excitatory amino acids to stimulate prolactin secretion when administered to adult animals is hypothesized to depend on a central site of action in the brain, but there are no data to support this position. An alternative hypothesis was tested that glutamate would stimulate prolactin release when applied directly to primary cultures of dispersed adult female rat anterior pituitary cells studied in a perifusion protocol. Glutamate increased the rate of prolactin release within two minutes in a self-limited manner. Glutamate-stimulated prolactin release was augmented about 4-fold by elimination of magnesium from the perfusate and was associated with stimulation of pituitary calcium flux. Ketamine and MK-801 both reduced the basal rate of prolactin release and abolished the effects of glutamate. Pituitary cells of 10-day-old rats responded similarly to glutamate. Exposure to glutamate did not influence subsequent responses to physiological hypothalamic secretagogues, thus the likelihood of toxicity was minimized. These results suggest that the N-methyl-D-aspartate (NMDA) subclass of the glutamate receptor complex is involved. Prolactin secretion may be regulated physiologically through a functional glutamate receptor on pituitary cells.     

The effects of 5-hydroxytryptophan and 5-hydroxytryptamine on dopamine synthesis and release in rat brain striatal synaptosomes.

The effects of 5-hydroxytryptophan (5-HTP) and serotonin (5-HT) on dopamine synthesis and release in rat brain striatal synaptosomes have been examined and compared to the effects of tyramine and dopamine. Serotonin inhibited dopamine synthesis from tyrosine, with 25% inhibition occurring at 3 μM-5-HT and 60% inhibition at 200 μM. Dopamine synthesis from DOPA was also inhibited by 5-HT, with 30% inhibition occurring at 200 μ. At 200 μM-5-HTP, dopamine synthesis from both tyrosine and DOPA was inhibited about 70%. When just the tyrosine hydroxylation step was measured in the intact synaptosome, 5-HT, 5-HTP, tyramine and dopamine all caused significant inhibition, but only dopamine inhibited soluble tyrosine hydroxylase [L-tyrosine 3-monooxygenase; L-tyrosine, tetrahydropteridine oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2] prepared from lysed synaptosomes. Particulate tyrosine hydroxylase was not inhibited by 10 μM-5-HT, but was about 20% inhibited by 200 μM-5-HT and 5-HTP. At 200 μM both 5-HT and 5-HTP stimulated endogenous dopamine release. These experiments suggest that exposure of dopaminergic neurons to 5-HT or 5-HTP leads to an inhibition of dopamine synthesis, mediated in part by an intraneuronal displacement of dopamine from vesicle storage sites, leading to an increase in dopamine-induced feedback inhibition of tyrosine hydroxylase, and in part by a direct inhibition of DOPA decarboxylation.     

Disaggregation of brain polysomes by L-5-hydroxytryptophan: Mediation by serotonin

In rats, intraperitoneal administration of L-5-hydroxytryptophan (200 mg/kg) causes extensive disaggregation of whole brain polysomes after one hour. Polysome disaggregation is prevented if the conversion of L-5-hydroxytryptophan to serotonin is blocked by pretreatment with an aromatic L-amino acid decarboxylase inhibitor; disaggregation is potentiated by pretreatment with a monoamine oxidase inhibitor. The brain polysome disaggregation induced by L-phenylalanine administration (1 g/kg) is not blocked by decarboxylase inhibition.     

Stimulation of prolactin release in rats by GABA.

Infusion of GABA into the lateral ventricle of intact female rats on the morning of proestrus and in ovariectomized rats significantly stimulated PRL release. This response apparently is not mediated through a direct action on the pituitary since injection of GABA into hypophysectomized rats with a pituitary transplant under the kindney capsule did not alter serum prolactin levels. These observations suggest that GABA may have a role in regulating prolactin secretion.