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

Previous data have clearly suggested that the posterior pituitary (PP), consisting of neural lobe (NL) and intermediate lobe (IL), has a role in the control of anterior pituitary PRL secretion. However, basic aspects of this regulatory mechanism like (1), the role of an intact hypothalamic innervation of the PP as well as (2) the site of production of previously found PRL releasing substance(s) have not yet been characterized. Denervation of the PP (PPD) is an effective method for having a selective lesion of the innervation of PP, indeed, PPD results in a disappearance of neurosecretory materials from NL and tyrosine hydroxylase (TH) immunoreactivity from IL, leaving blood supply of all three lobes intact. Blood samples were taken from freely moving sham an PP-denervated lactating rats before and after 4-h separation from their pups and during the suckling stimulus. PPD blocks separation-induced depletion but only attenuates suckling induced release of PRL. Furthermore, it doubles plasma level of alpha-MSH during the entire sampling period, which has been used as a marker for in vivo secretory activity of IL cells. Lack of the separation-induced depression in plasma PRL of PPD animals can be partially restored by normalizing the diabetes insipidus with treatment of a vasopressin analogue, 1-desamino-8-D-arginine-vasopressin (dDAVP). In contrast, dDAVP, neither alone nor in combination with oxytocin (OXY), can change PPD-induced elevation of plasma alpha-MSH as well as attenuation of PRL response induced by suckling. It is concluded that: (1) contribution of the THDA system parallel to the confirmed role in the regulation of alpha-MSH seems to be crucial for the depletion of plasma PRL induced by separation but not for the elevation due to suckling stimulus, (2) intact hypothalamic innervations of both NL and IL, regulating water intake and the secretion of alpha-MSH, respectively, are necessary for normal secretory responses of AL during lactation, (3) as well as for the presence of PRF activity in PP, (4) which does not solely responsible for suckling-induced PRL release. Therefore, an interplay between several substances produced by NIL of the pituitary gland must have been responsible for the intact regulation of PRL secretion during lactation.
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PMID:Effect of posterior pituitary denervation (PPD) on prolactin (PRL) and alpha-melanocyte-stimulating hormone (alpha-MSH) secretion of lactating rats. 922 42

When exposed to short-day conditions, hamsters and other long-day breeders undergo gonadal regression. With chronic exposure to short days, however, the animals become photorefractory and gonadal recrudescence occurs. The underlying mechanism for this insensitivity is still unknown. There is growing evidence, however, that specific cells of the pituitary pars tuberalis (PT) mediate these photoperiod/nonphotoperiod-dependent changes as a direct or indirect "Zeitgeber" for the endocrine system. We investigated messenger RNA (mRNA)/protein formation for several hypophyseal hormones (beta-TSH, beta-LH, PRL, common alpha-chain) in the pars distalis (PD) and PT of female Djungarian hamsters in long photoperiod (LP) and after 18, 28, and 38 weeks of short photoperiod (SP). As indicated by gonadal and body weight, the hamsters displayed gonadal regression after 18 and 28 weeks of SP; after 38 weeks of SP, all animals showed recrudescence. At 18 and 28 weeks of SP, only PRL mRNA and protein levels were significantly reduced in the PD and returned to LP values after 38 weeks of SP. The expression of hypothalamic tyrosine hydroxylase in the arcuate nucleus that was determined by immunocytochemistry and by in situ hybridization was also down-regulated in SP18 and SP28 with increasing levels at SP38. Urinary 6-sulfatoxymelatonin levels were elevated in SP with highest levels in the SP18 group. In the PT, beta-TSH mRNA and protein were not detectable in all SP groups compared with the moderate signal intensity in LP. The common alpha-chain mRNA and protein, however, which were also reduced in the animals of the SP18 group, were already elevated after 28 weeks of SP and nearly reached LP-levels after 38 weeks of SP. These results show that, in contrast to LH and TSH, PRL expression in the PD is a sensitive indicator for photoperiod dependent changes of the endocrine system and seems to be tyrosine hydroxylase independent. The increase of common alpha-chain expression in PT-specific cells depending upon duration of SP that precedes the hormonal changes in the PD leads us to speculate that PT-specific cells initiate spontaneous recrudescence via a PT-PD pathway.
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PMID:Initial expression of the common alpha-chain in hypophyseal pars tuberalis-specific cells in spontaneous recrudescent hamsters. 932 18

Chronic exposure of F344 rats to diethylstilbestrol (DES) induces pituitary tumors (DES-T) composed of proliferating lactotrophs. Presently, we studied the effect of progestins on parameters related to tumor growth and function, due to previous evidences of progesterone antagonism of pituitary tumorigenesis acting at pituitary and hypothalamic levels [Piroli, G., Grillo, C., Ferrini, M., Lux-Lantos, V. and De Nicola, A. F., Antagonism by progesterone of diethylstilbestrol-induced pituitary tumorigenesis in Fischer 344 rats: Effects on sex steroid receptors and tyrosine hydroxylase mRNA, Neuroendocrinology, 1996, 63, 530-539]. In search of a quantitatively more important effect, animals bearing DES-T were treated with synthetic progestins. Competition assays using DES-T as source of progestin receptors indicated that levonorgestrel (LNG), gestodene and R5020 showed higher affinities (IC50 1-2 nM) than progesterone, norethisterone and medroxyprogesterone (IC50 10-25 nM). Treatment with LNG reduced DES-T weight by 45%, and serum PRL by one half. Small (monomeric) and big (polymeric) PRL increased 5- and 2.5-fold, respectively, in DES-T in comparison with pituitaries of ovariectomized (OVX) rats. However, LNG produced no changes indicating that synthesis and storage of PRL was conserved in rats receiving both hormonal treatments. DES induced a 15-fold increase in cell proliferation, measured as bromodeoxyuridine incorporation into cell nuclei, in comparison to OVX rats, while LNG treatment of DES-T bearing rats reduced this index by 72%. Electron microscopic images showed that LNG markedly reduced hypertrophy and hyperplasia of lactotropes, increasing the proportions of degenerating cells and cells of high electronic density with alterations of cytoplasmic organelles. However, histopathological signs of apoptosis were absent. Therefore, reduced cell proliferation and non-apoptotic cell death are part of the mechanisms employed by progestins to antagonize tumorigenesis at the pituitary level. The results may open a new therapeutic strategy for treatment of PRL secreting adenoma in humans.
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PMID:Mechanisms in progestin antagonism of pituitary tumorigenesis. 956 11

Serotonin is known to stimulate prolactin secretion by decreasing tyrosine hydroxylase (TH) activity in the tuberoinfundibular dopaminergic (TIDA) neurons. However, the effects of aging on the responsiveness of TIDA neurons to serotonin are not known. An effective way to increase serotonergic activity is to administer 5-hydroxytryptophan (5-HTP), a serotonin precursor. The present study was done to investigate the effects of 5-HTP on TIDA neuronal activity in aging animals. Middle-aged (10-12 mo), old (18-20 mo), and very old (22-24 mo) female Sprague-Dawley rats were bilaterally ovariectomized. Ten days later, they were injected iv with 50 mg/kg body wt of 5-HTP or the vehicle for 5-HTP (PBS-HCI). Twenty minutes later, m-hydroxybenzylhydrazine (NSD), a DOPA decarboxylase inhibitor, was administered. Ten minutes later, the animals were killed, and tyrosine hydroxylase (TH) activity was determined by measuring L-DOPA accumulation in the stalk median eminence by HPLC-EC. In all three groups, administration of 5-HTP increased serum prolactin levels significantly. In control middle-aged rats, TH activity (L-DOPA pg/ microg protein) was 33.0+/-5.6. Treatment with 5-HTP decreased TH activity by 60%. Similarly, 5-HTP treatment decreased TH activity by 52 and 56% in 18- to 20- and 22- to 24-mo-old rats, respectively, compared to the control rats. The magnitudes of the 5-HTP-induced decreases in TH activities in middle-aged, old, and very old rats were not different from each other. These results indicate that TIDA neuronal responsiveness to serotonin does not change with age and that 5-HTP is capable of stimulating PRL release even in very old rats.
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PMID:Responsiveness of tuberoinfundibular dopaminergic neurons to 5-hydroxytryptophan: effects of aging. 979 28

During lactation the suckling stimulus increases the activity of two populations of neuropeptide Y (NPY) neurons in the hypothalamus, the caudal portion of the arcuate nucleus (ARH) and the dorsomedial hypothalamus (DMH), and suppresses the activity of TIDA neurons in the ARH. In the present study, an acute resuckling model was used to examine the role of suckling-induced hyperprolactinemia in modulating the activity of these systems. Lactating rats were deprived of their eight-pup litters on day 9 postpartum, and 48 h later, the animals served either as nonsuckled controls (0 pups) or were suckled for 24 h. In addition, some of the resuckled animals received two s.c. injections of bromocriptine (0.5 mg/rat x injection), a dopamine D2 agonist, to inhibit suckling-induced PRL secretion. In situ hybridization was performed for rat NPY messenger RNA (mRNA) and tyrosine hydroxylase (TH) mRNA to provide an index for NPY and TIDA neuronal activities, respectively. Resuckling for 24 h induced a significant increase in NPY mRNA levels in the caudal portion of the ARH and in the DMH. Bromocriptine treatment did not alter the increase in NPY mRNA levels in the ARH, whereas the treatment greatly attenuated the increase in NPY mRNA in the DMH. TH mRNA levels in the rostral ARH area returned to basal levels in the nonsuckled control animals, and 24 h of resuckling significantly suppressed TH mRNA expression in this area. Bromocriptine treatment caused a significant increase in TH mRNA levels compared with those in the eight-pup suckled group. Thus, the results from the present study demonstrate that the suckling stimulus activated the two populations of NPY neurons and suppressed TIDA activity. Suckling-induced hyperprolactinemia did not participate in the increase in ARH NPY activity, whereas it played a major stimulatory role in suckling-induced activation of NPY neurons in the DMH and an inhibitory role in suckling-induced suppression of TIDA activity. The increase in TIDA activity after bromocriptine treatment was unexpected and suggests that the role of PRL in the regulation of TIDA activity is significantly altered during lactation.
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PMID:Neuropeptide Y and tuberoinfundibular dopamine activities are altered during lactation: role of prolactin. 988 15

PRL in the rat exerts its luteotropic action during the first half of pregnancy. After midpregnancy, placental lactogens (PLs) take the place of PRL to stimulate progesterone secretion from the corpus luteum. Simultaneously, PLs trigger a negative feedback on PRL secretion. However, the brain mechanisms for the negative feedback induced by PLs are not fully understood. Here, we report changes in plasma PRL levels, tuberoinfundibular dopaminergic (TIDA) neuronal activity as measured by Fos-related antigen (FRA)/tyrosine hydroxylase (TH) immunoreactivity, and TH catalytic activity as measured by dihydroxyphenylalanine (DOPA) accumulation in the stalk-median eminence (SME) after experimental manipulation of PL levels. On day 4 of pregnancy, animals received Rcho-1 cells intracerebroventricularly (i.c.v.) to increase the level of PLs in the brain or HRP-1 cells as controls. On day 12 of pregnancy, hysterectomy alone or i.c.v. HRP-1 injection plus hysterectomy were performed to remove the source of PLs. Rcho-1 i.c.v. injection plus hysterectomy were performed to examine the effect of replacement of the PL source. Sham-hysterectomized animals were used as a control group. Animals were killed 2 days after each treatment at 0200 and 1800 h, which represent the peak times of PRL surges, and at 1400 h, which represents the intersurge time, by either transcardial perfusion for FRA/TH immunocytochemistry or decapitation 30 min after NSD 1015 injection to assess DOPA accumulation with HPLC-electrochemical detection. Rcho-1 cells completely abolished PRL surges on day 6 of pregnancy and increased the percentage of FRA/TH immunoreactivity in the dorsomedial, ventrolateral, and caudal subdivisions of the arcuate nucleus. This change in neuronal activity reflected the amount of DOPA accumulation in the SME, which was high at all time points. On day 14 of pregnancy, removal of the PL source by hysterectomy resulted in increased PRL levels and decreased neuronal activity of TIDA neurons at all three time points. Similar profiles were observed in animals that received i.c.v. HRP-1 injection plus hysterectomy. Replacement of the source of PL with Rcho-1 cells in hysterectomized rats resulted in low PRL secretion, high neuronal activity of TIDA neurons, and high TH catalytic activity. These patterns were the same as those in sham-operated animals. Our results demonstrate that PLs induce an increase in the neuronal activity of dopaminergic neurons, as measured by FRA/TH immunoreactivity and TH catalytic activity in the SME. Removal of the PL source elevates plasma PRL levels at all times during the second half of pregnancy and does not restore PRL surges.
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PMID:Feedback effects of placental lactogens on prolactin levels and Fos-related antigen immunoreactivity of tuberoinfundibular dopaminergic neurons in the arcuate nucleus during pregnancy in the rat. 1021 67

The human GH-releasing hormone (hGHRH) transgenic mouse has a hyperplastic anterior pituitary gland that eventually develops into an adenoma. We showed previously that the number of lactotrophs in the male hGHRH transgenic mouse is increased 2-fold, yet there is no concomitant increase in plasma levels of PRL. To further elucidate underlying changes in lactotroph function in the hGHRH transgenic mouse, the objectives of this study were to 1) examine the relative differences in PRL gene expression in transgenic mice and their siblings, 2) quantify PRL secretion at the level of the individual cell, 3) determine whether tyrosine hydroxylase gene expression and/or activity are altered in the hypothalamus of transgenic mice, and 4) assess dopamine receptor gene expression and functional sensitivity in lactotrophs of transgenic mice. Total PRL messenger RNA (mRNA) levels were increased nearly 5-fold in the hGHRH transgenic mouse, whereas the concentrations of PRL mRNA (PRL mRNA per microg total RNA) were unchanged. In contrast, total PRL contents were unchanged, whereas the concentrations of PRL (micrograms of PRL per mg total protein) were decreased 3-fold. Hypothalamic tyrosine hydroxylase steady state mRNA levels were not altered in the hGHRH transgenic mice, but hypothalamic tyrosine hydroxylase activity was increased 2-fold in transgenic mice. Dopamine D2 receptor mRNA concentrations in the anterior pituitary were increased 2.5-fold in hGHRH transgenic mice, and total pituitary D2 receptor mRNA levels were increased nearly 10-fold. Furthermore, the basal secretory capacity of lactotrophs from transgenic mice was increased significantly at the level of the single cell, and dopamine inhibited the secretion of PRL to a greater extent in hGHRH transgenic mice. Thus, although the total number of lactotrophs is increased 2-fold in hGHRH transgenic mice, the present data are consistent with the hypothesis that increased hypothalamic dopamine synthesis and release coupled with an increase in D2 dopamine receptor gene expression and functional sensitivity in the pituitary result in normal plasma levels of PRL.
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PMID:Pituitary hormone gene expression and secretion in human growth hormone-releasing hormone transgenic mice: focus on lactotroph function. 1061 26

Three populations of hypothalamic neuroendocrine dopaminergic (NEDA) neurons, arising from the arcuate and periventricular nuclei of the hypothalamus release dopamine (DA) that acts at the pituitary gland to regulate the secretion of PRL. It is generally accepted that NEDA neurons lack functional DA transporters (DATs), which are responsible for uptake of DA from the synaptic cleft into the presynaptic axon terminal. This study localized DATs to the hypothalamo-pituitary axis and evaluated the effect of DAT blockade on the hypothalamo-pituitary regulation of PRL. After 7 days of treatment with cocaine (a nonspecific amine transporter blocker) or mazindol (a specific DAT blocker), the relative abundance of PRL messenger RNA (mRNA) in the anterior lobe (AL) of OVX rats was significantly decreased, whereas the relative abundance of tyrosine hydroxylase mRNA in the hypothalamus was significantly increased. The effect of cocaine or mazindol administration on DA turnover and serum PRL concentration was examined in estradiol (E2)-treated OVX rats. E2 administration (i.v.) resulted in a significant increase in serum PRL within 4 h; however, cocaine or mazindol administration abolished the E2-induced increase of PRL. Cocaine or mazindol significantly increased the concentration of DA at the site of the axon terminals within the median eminence (ME), intermediate lobe (IL) and neural lobe (NL), indicating blockade of uptake. Because formation of DOPAC requires uptake of DA, concentrations of DOPAC in the ME, IL and NL decreased following treatment with either cocaine or mazindol. These data, together with the presence of immunopositive DAT in the ME, pituitary stalk, IL, and NL, suggest that a functional DAT system is present within all three populations of NEDA neurons. Moreover, similarity between the effects of cocaine and mazindol treatment indicate that blockade of the DAT, but not other amine transporters, is responsible for suppression of PRL gene expression and secretion. Blockade of DATs prevent uptake of DA into NEDA neurons and consequently increases the amount of DA that diffuses into the portal vasculature and reaches the AL. These data provide evidence that DATs play a physiological role in the regulation of DA release from and TH expression in NEDA neurons and consequently PRL secretion and PRL gene expression and further support our previous observation that the regulation of PRL secretion involves all three populations of NEDA neurons.
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PMID:Dopamine transporters participate in the physiological regulation of prolactin. 1061 59

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.
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PMID:Effects of prolactin on expression of Fos-related antigens in tyrosine hydroxylase-immunoreactive neurons in subdivisions of the arcuate nucleus. 1070 May 58

A1/A2 noradrenergic neurons in the medulla oblongata are well known to mediate stress signals in the central nervous system. Stress activates A1/A2 noradrenergic neurons, and then noradrenaline (NA) stimulates ACTH secretion through hypothalamic CRH. On the other hand, PRL-releasing peptide (PrRP) was recently isolated and was found to be produced by some A1/A2 neurons and the dorsomedial hypothalamic nucleus. We previously demonstrated that PrRP neurons make synapse-like contact with hypothalamic CRH neurons. In fact, we demonstrated that the central administration of PrRP stimulates CRH-mediated ACTH secretion. Furthermore, it has been reported that PrRP neurons in A1/A2 cell groups are colocalized with tyrosine hydroxylase (TH), which is known as the marker enzyme of catecholaminergic neurons. These data strongly suggest that PrRP is related to stress-responsive signal transduction, and PrRP and NA cooperatively modulate the hypothalamo-pituitary-adrenal axis. We therefore examined the effect of water immersion-restraint stress on c-Fos protein accumulation in PrRP- and TH-immunoreactive neurons. The synergistic effects of PrRP and NA on plasma ACTH elevation were also examined. The results clearly showed that c-Fos protein accumulation dramatically increased in the nuclei of A1/A2 and dorsomedial hypothalamic nucleus PrRP neurons. In addition, it was revealed that c-Fos protein was specifically expressed in the PrRP/TH double positive cells in the A1/A2 cell groups. We also demonstrated that the central administration of PrRP and NA in combination at subactive (noneffective) doses clearly induced plasma ACTH elevation. Here we report that PrRP is a novel and important mediator of the hypothalamo-pituitary-adrenal axis for the stress response.
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PMID:Prolactin-releasing peptide as a novel stress mediator in the central nervous system. 1131 70


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