Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.16.2 (tyrosine hydroxylase)
 14,760 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prolactin can modulate the adrenal medulla function, but it has not yet been established whether its action is directly exerted on the adrenal medulla cells. In this work, we have studied the effect of several concentrations of prolactin on the synthesis, storage and release of norepinephrine and epinephrine using cultured bovine adrenal chromaffin cells. In these cells, prolactin inhibited the activity of tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine synthesis, in a dose-dependent manner, from a concentration above 50 ng/ml of prolactin in the incubation medium. Surprisingly, this dose-dependent decrease was not accompanied by changes in the catecholamine release, since the secretion of both norepinephrine and epinephrine as well as the total catecholamine secretion were not significantly altered by the different prolactin concentrations. Moreover, the cellular content of both catecholamines was not altered by prolactin. In summary, these observations allow us to conclude that prolactin exerts a direct inhibitory effect on the tyrosine hydroxylase activity in cultured adrenal chromaffin cells without altering catecholamine release.
 ...
PMID:Prolactin inhibits the activity of tyrosine hydroxylase in cultured bovine adrenal chromaffin cells in a dose-dependent manner. 197 93

1. Prolactin (PRL) can play a role as a physiological modulator of adrenal medulla function in several rodents. 2. We have examined the effects of hyperprolactinemia induced by ectopic pituitary grafts in Syrian hamsters on the adrenal medulla contents of catecholamines (CA) and their metabolites, as well as on the activities of several enzymes involved in the metabolism of these amines. 3. Increases in the peripheral levels of PRL in these animals were associated with decreases in adrenal medulla weight and increases in adrenal medulla contents of norepinephrine, epinephrine and vanilmandelic acid, the main degradative metabolite of CA, while adrenal medulla contents of the O-methylated derivatives of CA, normetanephrine and metanephrine, were unaltered. 4. These changes were correlated with increases in the adrenal medulla activity of monoamine oxidase, while the activities of tyrosine hydroxylase, phenylethanolamine-N-methyl transferase and catechol-O-methyl transferase were unaltered. 5. These results indicate that PRL is able to act on the adrenal medulla of hamsters by increasing the ability of these cells to metabolize CA via oxidative deamination.
 ...
PMID:Changes in the catecholamine metabolism in the adrenal medulla of male hamsters with experimental hyperprolactinemia. 257 85

Prolactin (PRL) secretion by the anterior pituitary gland is dependent upon the tonic inhibitory influence of the tuberoinfundibular dopaminergic (TIDA) neuronal system. TIDA neurons, in turn, are regulated by various afferent neuronal systems. To support the concept that the recently-discovered neuropeptide, galanin (GAL), is one of the neurotransmitter/neuromodulator substances which might synaptically regulate the function of the TIDA system, immunocytochemical double-labeling studies were carried out in the hypothalamic arcuate nucleus (AN) of the male rat. The analysis of light microscopic preparations revealed the overlapping of GALergic and dopaminergic (detected by tyrosine hydroxylase immunoreactivity) neuronal elements in both the dorsomedial and ventrolateral parts of the AN. TH-containing perikarya and dendrites were contacted by varicose GAL-IR axons in these regions. The electron microscopic studies of ultrathin sections demonstrated axosomatic and axodendritic synapses between GALergic axons and TH-IR neurons. These findings support the view that GAL may modulate PRL release, acting as a neurotransmitter/neuromodulator in synaptic afferents to the TIDA system.
 ...
PMID:Galanin-containing axons synapse on tyrosine hydroxylase-immunoreactive neurons in the hypothalamic arcuate nucleus of the rat. 752 19

The tuberoinfundibular dopaminergic (TIDA) neurons projecting to the external zone of the median eminence arise in the dorsomedial and ventrolateral subdivisions of the arcuate nucleus. In cycling female rats these regoins contain only scattered enkephalin-immunoreactive (ENK-i) neurons some of which coexpress dopamine, detected by immunostaining for tyrosine hydroxylase (TH). The present immunocytochemical, in situ hybridization and retrograde-labeling studies show that each TIDA neuron of pregnant, pseudopregnant, lactating, and aged female rats contains ENK-like immunoreactivity and pro-ENK mRNA and projects to the hypophysial portal circulation. Ovariectomy of lactating and aged rats did not change ENK staining within TIDA neurons, suggesting that ovarian steroids do not play a critical role in the colocalization of ENK and dopamine. Since prolactin levels are elevated in each of these experimental animals, a possible role for prolactin in the induction of the ENK gene in TIDA neurons is suggested. Prolactin stimulates dopamine and its own secretion via a short-loop feedback mechanism. The sensitivity of this regulatory mechanism is altered in these experimental animals, resulting in elevated prolactin secretion. ENK, which has prolactin-releasing activity and is colocalized with dopamine, could mediate the positive short-loop feedback regulation and sustain elevated levels of prolactin in pregnant, pseudopregnant, lactating, and aged animals.
 ...
PMID:Induction of enkephalin in tuberoinfundibular dopaminergic neurons of pregnant, pseudopregnant, lactating and aged female rats. 796 76

In the sheep, photoperiod, through melatonin, and oestradiol negative-feedback are two major regulators of seasonal changes in luteinizing hormone (LH) and prolactin secretion. Melatonin and oestradiol act on dopamine neurons of the hypothalamus to modify the enzymatic activity of tyrosine hydroxylase (TH). To further understand how melatonin and oestradiol regulate TH activity, we have studied the level of TH mRNA by in situ hybridization with an homologous cDNA probe, in A12 and A15 dopamine neurons of four groups of ovariectomized ewes: long-day exposed ewes with or without subcutaneous oestradiol implants and short-day exposed ewes with or without oestradiol. Results were analysed in relation to the concentration of LH and prolactin in the peripheral circulation. In the A15 cell group, TH mRNA levels were elevated in the short-day, oestradiol-treated ewes compared to all other groups. In this group, the level of TH mRNA was elevated simultaneously with LH concentration. The low level of TH mRNA found in the long-day, oestradiol-treated ewes may indicate that the increase of TH enzymatic activity previously reported by this treatment is not caused by an increase of the level of enzyme. In the A12 cell group, the level of TH mRNA in both long-day and short-day oestradiol-treated ewes was significantly higher than in ewes without oestradiol replacement. Prolactin concentrations were not correlated with TH mRNA variations in the A12 cell group.
 ...
PMID:Effect of oestradiol and photoperiod on TH mRNA concentrations in A15 and A12 dopamine cell groups in the ewe. 951 59

Prolactin (PRL) secretion is under the inhibitory regulation of the tuberoinfundibular dopaminergic (TIDA) system. Short-term elevation in PRL levels has been shown to increase the activity of TIDA neurons, however, the responsiveness of TIDA neurons to chronically elevated serum PRL levels is controversial. The purpose of this study was to investigate the effects of prolonged elevations of serum PRL on TIDA neuronal activity. Female Sprague-Dawley rats (2-3 months old) were ovariectomized and implanted (s.c.) with haloperidol (HAL), a dopamine receptor antagonist for 6 or 9 months to produce hyperprolactinemia. Ovariectomized, sham-implanted rats were used as controls. Other groups of intact rats were implanted with HAL or sham-implanted for 9 months and then were implanted with PRL-producing MMQ cells for 6 weeks to further increase circulating PRL levels. TIDA neuronal activity was measured in terms of tyrosine hydroxylase (TH) activity in the stalk-median eminence and was correlated with changes in serum PRL levels. After 6 months of treatment, TH activity in HAL-treated rats was 130% higher than that in the control rats. After 9 months of treatment, TH activity in HAL-treated rats was 81% higher than that in control rats. This increase was significantly less than the increase that occurred after 6 months of treatment. Nine months of HAL-induced hyperprolactinemia followed by implantation of PRL-producing MMQ cells, which resulted in very high levels of PRL, did not increase TH activity in the stalk-median eminence. These results demonstrate that hyperprolactinemia over a prolonged period reduces the responsiveness of TIDA neurons, and these effects vary depending on the duration and intensity of hyperprolactinemia.
 ...
PMID:Effects of chronic hyperprolactinemia on tuberoinfundibular dopaminergic neurons. 952 Oct 94

Dual immunohistochemistry was employed to determine the effects of prolactin on expression of Fos and its related antigens (FRA) in tuberoinfundibular dopamine (TIDA) neurons located in the dorsomedial (DM) and ventrolateral (VL) subdivisions of the arcuate nucleus (ARC) in the male rat. Systemic administration of the DA receptor antagonist haloperidol caused a sustained (up to 12 h) increase in plasma prolactin concentrations that was accompanied by a transient increase (at 3 h) in the percentage of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons containing FRA-IR nuclei in the DM-ARC. In contrast, haloperidol caused a prolonged (1. 5 to 12 h) decrease in the percentage of TH-IR neurons with FRA-IR nuclei in the VL-ARC. Haloperidol had no effect, however, on the overall number of TH-IR neurons in either of these regions. Co-administration of prolactin antisera (PRL-AB) blocked haloperidol-induced increases in both plasma prolactin concentrations and the percentage of TH-IR neurons expressing FRA in the DM-ARC, but had no effect on haloperidol-induced inhibition of FRA expression in TH-IR neurons in the VL-ARC. Intracerebroventricular (i.c.v.) administration of prolactin also increased the percentage of TH-IR neurons containing FRA-IR nuclei in the DM-ARC, but this effect was of longer duration (up to 6 h) than that of haloperidol in all but the most caudal portion of the DM-ARC. In the VL-ARC, prolactin caused a transient increase (at 1.5 h) in the percentage of TH-IR containing FRA-IR nuclei. These results demonstrate that prolactin regulates immediate early gene expression in TIDA neurons in male rats, and reveal that there are temporal differences in the responsiveness of discrete subpopulations of these neurons to prolactin. Prolactin causes a short-lived increase in FRA expression in TIDA neurons in the VL-ARC which is followed by a more prolonged activation of FRA expression in TIDA neurons in the DM-ARC.
 ...
PMID:Effects of prolactin on expression of Fos-related antigens in tyrosine hydroxylase-immunoreactive neurons in subdivisions of the arcuate nucleus. 1070 May 58

Prolactin release from the anterior pituitary is regulated principally by inhibitory influences imparted by the tuberoinfundibular dopamine system. Stimulatory control is provided by several hypothalamic, peripheral and local factors. Recently a new peptide, prolactin releasing peptide (PrRP), showing prolactin-secretagogue effects was discovered, synthesized and found to be expressed in brain. We have used histochemical and axonal transport methods to characterize the distribution of PrRP mRNA in the rat brain, and to identify possible pathways through which this factor might be delivered to the anterior lobe of the pituitary and thereby participate in the regulation of prolactin secretion. Analysis of histochemical preparations indicated that apart from a small population of cells in a non-neurosecretory portion of the hypothalamus, PrRP mRNA is expressed exclusively in the caudal part of the nucleus of the solitary tract and in the caudal ventrolateral medulla. All medullary PrRP expressing cells could be immunolabeled for tyrosine hydroxylase, and none were found to stain for glucagon-like peptide-1, identifying them as comprising subsets of A2 and A1 noradrenergic neurones, respectively. Numerous PrRP-expressing cells were retrogradely labelled following tracer injections in the paraventricular nucleus, while only a handful were backfilled following intravenous injections of tracer, indicating that this population issues substantial projections to the endocrine hypothalamus and meager ones to the median eminence and/or posterior pituitary. This conclusion was supported by the results of experiments in which the anterograde tracer, biotinylated dextran-amine, was injected into the PrRP cell group in the nucleus of the solitary tract. These findings suggest that PrRP expressing neurones display a highly restricted distribution, and are in a position to regulate the output of particular cell types in the endocrine hypothalamus. Whether and how PrRP might be delivered to the anterior pituitary remains to be determined.
 ...
PMID:Prolactin-releasing peptide is expressed in afferents to the endocrine hypothalamus, but not in neurosecretory neurones. 1071 8

Prolactin plays major roles in maintaining the corpora lutea of pregnancy and in the synthesis of milk during lactation. The hypothalamic mechanisms involved in these functions have been investigated. Mating leads to a surge of prolactin and programs daily surges during early pregnancy. The expression of Fos-immunoreactivity shows that mating activates several hypothalamic nuclei, particularly the arcuate nucleus and medial preoptic area. In the arcuate nucleus, mating is associated with Fos expression in beta-endorphin neurons, and infusion of naloxone blocks both mating-induced and diurnal prolactin surges. Tyrosine hydroxylase-immunoreactive dopamine neurons appear not to participate in surge generation. However, after day 10 of gestation the secretion of placental lactogens suppresses prolactin secretion via activation of dopamine neurons without involvement of beta-endorphin neurons. Intracerebroventricular implantation of placental lactogen-secreting cells will block pregnancy prolactin surges, increase Fos expression in dopamine neurons, and increase tyrosine hydroxylase activity. During lactation the mechanisms regulating dopamine and beta-endorphin neurons are further modified. In early lactation a prolactin-induced increase in tyrosine hydroxylase activity leads to negative feedback, but this effect is lost by mid-lactation. Overriding this negative feedback is the inhibitory effect that suckling has on dopaminergic activity. This may involve beta-endorphin-mediated inhibition of dopamine neurons, as naloxone causes a marked increase in tyrosine hydroxylase activity and suppression of circulating prolactin. However, removal of tonic dopamine inhibition is not sufficient to account for the high levels of prolactin attained during lactation, and additional releasing factors are probably involved. In situ hybrization histochemistry for the most recent candidate, prolactin-releasing peptide, suggests that this may involve brain stem neurons that co-localize noradrenaline. Thus, prolactin secretion during pregnancy and lactation involve complex interactions of regulatory factors and plasticity of neuronal responsiveness.
 ...
PMID:Regulation of prolactin secretion during pregnancy and lactation. 1158 29

Prolactin-secreting adenomas are one of the most common types of intracranial neoplasm found in humans. The modalities of clinical treatment currently in use include D(2)-dopamine receptor agonists, surgery, and radiotherapy, and the success rates for treatment are good. However, there are prolactinomas that are difficult to treat. As an alternative, we have developed a gene therapy strategy in which the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase (TH), is overexpressed in the anterior pituitary (AP) gland. Because dopamine is known to have an inhibitory effect on lactotroph growth and prolactin secretion, we developed a system that would enable its local synthesis from freely available precursor amino acids. A dual adenovirus tetracycline-regulatable expression system was generated to control the production of TH. In the absence but not presence of the tetracycline analog doxycycline, TH expression was observed in AP tumor cell lines AtT20, GH3, and MMQ. In both primary AP cell cultures and the AP gland, in situ expression of TH was seen in lactotrophs, somatotrophs, corticotrophs, thyrotrophs, and gonadotrophs in the absence but not presence of doxycycline. The ability of this system to inhibit hyperprolactinemia and pituitary lactotroph hyperplasia was then assessed in a model of estrogen- or estrogen/sulpiride-induced pituitary tumors. In the absence but not presence of doxycycline, a 49% reduction in pituitary growth and 58% reduction in the increase of circulating prolactin levels were observed in estrogen, but not estrogen/sulpiride, treated rats. These results indicate that in situ dopamine enhancement gene therapy can be a useful tool for the treatment of prolactinoma. Dopamine synthesis can be tightly regulated and the therapeutic benefit of the system is only inhibited when local dopamine signaling is impaired.
 ...
PMID:Regulated, adenovirus-mediated delivery of tyrosine hydroxylase suppresses growth of estrogen-induced pituitary prolactinomas. 1173 44


1 2 3 Next >>