Tuberoinfundibular Dopaminergic System Research Articles

Chronic estrogen affects TIDA neurons through IL-1β and NO: effects of aging.

Women are chronically exposed to estrogens through oral contraceptives, hormone replacement therapy or environmental estrogens. We hypothesized that chronic exposure to low levels of estradiol-17β (E2) can induce inflammatory and degenerative changes in the tuberoinfundibular dopaminergic (TIDA) system leading to reduced dopamine synthesis and hyperprolactinemia. Young (Y; 3–4 months) and middle-aged (MA; 10–12 months) Sprague-Dawley rats that were intact or ovariectomized (OVX) were either sham-implanted or implanted with a slow-release E2 pellet (20 ng E2/day for 90 days). To get mechanistic insight, adult 3- to 4-month-old WT, inducible nitric oxide synthase (iNOS) and IL-1 receptor (IL-1R) knockout (KO) mice were subjected to a similar treatment. Hypothalamic areas corresponding to the TIDA system were analyzed. E2 treatment increased IL-1β protein and nitrate levels in the arcuate nucleus of intact animals (Y and MA). Nitration of tyrosine hydroxylase in the median eminence increased with E2 treatment in both intact and OVX animals. There was no additional effect of age. This was accompanied by a reduction in dopamine levels and an increase in prolactin in intact animals. E2 treatment increased nitrate and reduced dopamine levels in the hypothalamus and increased serum prolactin in WT mice. In contrast, the effect of E2 on nitrate levels was blocked in IL-1R KO mice and the effect on dopamine and prolactin were blocked in iNOS KO animals. Taken together, these results show that chronic exposure to low levels of E2 decreases TIDA activity through a cytokine-nitric oxide-mediated pathway leading to hyperprolactinemia and that aging could promote these degenerative changes.

Neuroendocrine system as therapeutic target of vitex agnus castus fruit extract for premenstrual syndrome

The article regards to neuroendocrine mechanisms of development of latent hyperprolactinemia in the patients with premenstrual syndrome (PMS) and to some aspects of its impact on water-salt metabolism and ovarian cyclicity. The author has proposed the concept of interrelation between neurotransmitters and regulatory peptides in neuroendocrine control of prolactin secretion in PMS patients with a special reference to the role of hypothalamic tubero-infundibular dopaminergic system and galanin. According to this concept, hypothalamic dopamine is communicative link between stress- and estrogen-induced prolactin secretions. Given the current knowledge on the PMS pathogenesis, usage of Cyclodynon and Mastodynon which contain a special Vitex Agnus Castus fruit extract with proved dopaminergic activity for treatment of PMS accompanied by latent hyperprolactinemia is reasonable and save

The state of the tuberoinfundibular dopaminergic system during modeling of parkinsonism in mice

Parkinson’s disease (PD) is one of the most widespread neurodegenerative diseases; it develops as a result of the death of dopaminergic (DA-ergic) neurons of the nigrostriatal system of the brain. It has been shown in autopsy material that the neurodegenerative process spreads to other populations of neurons of the peripheral and central nervous system. In PD patients the tuberoinfundibular DA-ergic system (TIDAS) undergoes degradation; however, no experimental models exist that can reproduce the combined degradation of the nitrostriatal system and the TIDAS. In this work, we analyzed the state of the TIDAS during presymptomatic and symptomatic stages of parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These stages of parkinsonism develop as a result of subthreshold and threshold degradation of the nigrostriatal DA-ergic system. To evaluate the morphofunctional state of the TIDAS, we determined: (a) the number of neurons with tyrosine hydroxylase (TH), a key enzyme of DA synthesis; (b) the sizes of the terminals of TH-positive axons; (c) the levels of TH in the neuronal somas and the terminals of axons; and (d) the contents of DA, noradrenaline, and 3,4-dihydroxyphenyl acetic acid. According to the data that was obtained during the presymptomatic stage, for the TIDAS no changes were found in all the measured parameters. During the symptomatic stage, we observed (a) a decrease in DA content by 50%; (b) a decrease in the level of TH protein in axonal terminals and an increase in neuronal somas; and (c) an increase in the turnover of DA by 149% as compared to the control. The data we obtained suggest that the functional activity of the TIDAS was insufficient; this was seen in the form of alterations of DA metabolism, a decrease in the level of synthesis, probably in axonal terminals, and compensatory acceleration of the functional cycle from synthesis to enzymatic degradation. Although no changes in the number of neurons and axons that express TH was found in the TIDAS, the question of organic degradation of the TIDAS in parkinsonism is still open because TH is a marker of not only DA-ergic neurons that degenerate in the presence of neurotoxins but also of non-DA-ergic neurons that are insensitive to neurotoxins. Thus, during experimental modeling of Parkinsonism, we observed at least the metabolic characteristics of TIDAS degradation only at the symptomatic stage of the disease.

Chronic estradiol exposure induces oxidative stress in the hypothalamus to decrease hypothalamic dopamine and cause hyperprolactinemia

Estrogens are known to cause hyperprolactinemia, most probably by acting on the tuberoinfundibular dopaminergic (TIDA) system of the hypothalamus. Dopamine (DA) produced by TIDA neurons directly inhibits prolactin secretion and, therefore, to stimulate prolactin secretion, estrogens inhibit TIDA neurons to decrease DA production. However, the mechanism by which estrogen produces this effect is not clear. In the present study, we used a paradigm involving chronic exposure to low levels of estradiol-17β (E(2)) to mimic prolonged exposures to environmental and endogenous estrogens. We hypothesized that chronic exposure to low levels of E(2) induces oxidative stress in the arcuate nucleus (AN) of the hypothalamus that contains TIDA neurons and causes nitration of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of DA. This results in a significant decrease in DA and consequently, hyperprolactinemia. To investigate this, adult, intact female cycling rats were implanted with slow-release E(2) pellets (20 ng/day) for 30, 60, or 90 days and were compared with old (16-18 mo old) constant estrous (OCE) rats. Chronic E(2) exposure significantly increased the expression of glial fibrillary acidic protein and the concentrations of interleukin-1β (IL-1β) and nitrate in the AN that contains perikarya of TIDA neurons and increased nitration of TH in the median eminence (ME) that contains the terminals. These levels were comparable to those seen in OCE rats. We observed a significant decrease in DA concentrations in the ME and hyperprolactinemia in an exposure-dependent manner similar to that seen in OCE rats. It was concluded that chronic exposure to low levels of E(2) evokes oxidative stress in the AN to inhibit TIDA neuronal function, most probably leading to hyperprolactinemia.

Estrogen inhibits tuberoinfundibular dopaminergic neurons but does not cause irreversible damage

Dopaminergic neurons of the hypothalamic tuberoinfundibular dopaminergic (TIDA) system exert a tonic inhibitory control on prolactin (PRL) secretion whereas estrogen, known to inhibit TIDA neuron function, has been postulated to be toxic to TIDA neurons when it is chronically high. In order to determine whether estrogen in high doses can cause permanent damage to TIDA function, we submitted young female rats to continue high doses of estrogen administered, either centrally (intrahypothalamic estrogen implants) or peripherally (subcutaneous estrogen implants or weekly intramuscular (i.m.) injections for 7 weeks), subsequently withdrawing the steroid and observing the evolution of lactotrophes, serum PRL and TIDA neurons. Serum PRL was measured by radioimmunoassay whereas tyrosine hydroxylase positive (TH+) neurons and PRL cells were morphometrically assessed in sections of fixed hypothalami and pituitaries, respectively. After 30 days, hypothalamic estrogen implants induced a significant increase in serum PRL, whereas TH+ neurons were not detectable in the arcuate-periventricular hypothalamic (ARC) region of estrogen-implanted rats. Removal of implants on day 30 restored TH expression in the ARC and brought serum PRL back to basal levels 30 days after estrogen withdrawal. Subcutaneous or i.m. administration of estrogen for 7 weeks induced a marked hyperprolactinemia. However, 30 weeks after estrogen withdrawal, TH neuron numbers in the ARC were back to normal and serum PRL returned to basal levels. After peripheral but not central estrogen withdrawal, pituitary weight and lactotrophic cell numbers remained slightly increased. Our data suggest that estrogen even at high doses, does not cause permanent damage to TIDA neurons.

Degeneration of dopaminergic neurons triggers an expression of individual enzymes of dopamine synthesis in non-dopaminergic neurons of the arcuate nucleus in adult rats

Non-dopaminergic neurons expressing individual complementary enzymes dopamine (DA) synthesis were shown to produce DA in cooperation [Ugrumov, M., Melnikova, V., Ershov, P., Balan, I., Calas A., 2002. Tyrosine hydroxylase- and/or aromatic l-amino acid decarboxylase-expressing neurons in the rat arcuate nucleus: ontogenesis and functional significance. Psychoneuroendocrinology 27, 533–548; Ugrumov, M.V., Melnikova, V.I., Lavrentyeva, A.V., Kudrin, V.S., Rayevsky, K.S., 2004. Dopamine synthesis by non-dopaminergic neurons expressing individual complementary enzymes of the dopamine synthetic pathway in the arcuate nucleus of fetal rats. Neuroscience 124, 629–635]. This study was aimed at testing our hypothesis that the cooperative synthesis of DA in non-dopaminergic neurons is an adaptive reaction under functional insufficiency of the dopaminergic system. Functional insufficiency of the tuberoinfundibular dopaminergic system was provoked by 6-OHDA-induced degeneration of dopaminergic neurons in the arcuate nucleus in adult rats. Bienzymatic (dopaminergic) neurons and monoenzymatic neurons expressing tyrosine hydroxylase (TH) or aromatic l-amino acid decarboxylase (AADC) were detected with a double-immunofluorescent technique on cryostat sections. The 6-OHDA-induced degeneration of dopaminergic neurons was accompanied by a significant increase of the number of monoenzymatic TH neurons and AADC neurons that appears to support our hypothesis. The reaction of bienzymatic and monoenzymatic neuron populations to the 6-OHDA administration occurred to be region-specific. The former disappeared in the dorsomedial region of the arcuate nucleus while the latter increased in the ventrolateral region. Thus, degeneration of dopaminergic neurons in the arcuate nucleus of adult rats is accompanied by the expression of individual enzymes of DA synthesis in non-dopaminergic neurons that may be an adaptive reaction.

Effects of the cocaine- and amphetamine-regulated transcript peptide on the turnover of dopamine in tuberoinfundibular neurons and serum prolactin levels: studies using estrogen, melanin concentrating hormone, and melanocortin

Effects of the cocaine- and amphetamine-regulated transcript (CART) peptide on tuberoinfundibular dopaminergic (TIDA) neurons were examined in female and male Sprague–Dawley rats in the morning and afternoon. We also examined the blocking effects of melanin concentrating hormone (MCH) and the antagonists of α-melanocyte stimulating hormone (α-MSH), SHU9119 and HS014, on stimulation induced by the CART peptide in TIDA systems. Intracerebroventricular administration of 1 μg CART peptide (55–102) at 45 min, either in the morning or afternoon, produced an increase in the median eminence (ME) DOPAC (3,4-dihydroxyphenylacetic acid) level and a corresponding decrease in serum prolactin (PRL) levels. This resulted from stimulation of TIDA neurons regardless of castration, and whether or not male and female rats were estrogen-primed. The stimulatory effects of the CART peptide on ME DOPAC levels were similar in the morning and afternoon in both male and female rats. Central treatment with 1 μg SHU9119, HS014, or MCH significantly decreased the ME DOPAC levels and elevated serum PRL levels in female rats. However, only MCH prevented the stimulatory effect of the CART peptide on TIDA neurons. These results indicate that stimulation by the CART peptide on TIDA neurons is gender-independent; and this stimulatory effect can be blocked by MCH, but not the antagonists of α-MSH.

Effect of intracerebroventricular injection of lipopolysaccharide on the tuberoinfundibular dopaminergic system of the rat

Numerous studies indicate that monoaminergic systems are sensitive to both peripheral and central inflammatory stimuli, and in particular dopaminergic neurons in the nigrostriatal system degenerate after local injection of lipopolysaccharide (LPS). However, data about the response of other dopaminergic groups to local inflammation are very sparse. In this study, we have examined the effect of i.c.v. injection of LPS on the tuberoinfundibular dopaminergic (TIDA) system by using biochemical and morphological parameters. Our results show that 6 h after i.c.v. injection of LPS, in parallel to a transient and intense immunoreaction to interleukin-1β in arcuate microglial cells, there is a decrease in tyrosine hydroxylase (TH) activity in the median eminence and in the number of TH- and TH mRNA-positive cells in the arcuate nucleus, and at 12 h, an increase of prolactin levels in serum. Posterior changes were found in the TH mRNA labeling pattern, mostly in the ventrolateral region of the arcuate nucleus, but they were not accompanied by any changes in TH activity and immunoreactivity and TH-cell count. This suggests that the TIDA system is functionally susceptible to local inflammation, but the effects are transient and do not induce neurodegeneration.

Central Administration of Orexin A Suppresses Basal and Domperidone Stimulated Plasma Prolactin

Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P < 0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 +/- 7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 +/- 4.3 ng/ml, both P < 0.005 vs i.p. domperidone + ICV saline 57.9 +/- 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system.

NMDA receptor antagonists block stress-induced prolactin release in female rats at estrus

In order to evaluate the role of glutamate in prolactin secretion, we examined the effects of N-methyl- d, l-aspartic acid (NMDA) receptor antagonists on serum prolactin levels at both resting and restraint-stress conditions in female rats at estrus. NMDA increased basal serum prolactin levels. Administration of the selective NMDA receptor antagonist, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) (5 and 10 mg/kg i.p.), to rats under resting conditions enhanced basal prolactin levels. A low dose of CGS 19755 (3 mg/kg) was unable to modify the hormone serum level. Under stress conditions the pretreatment with CGS 19755 (3 and 5 mg/kg) prevented the increase in serum prolactin levels. This effect was reversed by NMDA (60 mg/kg s.c.). The NMDA receptor antagonist (5 mg/kg) decreased the median eminence concentration of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), without modifying dopamine content. To examine the probable link between serotonin (5-HT) and glutamate in prolactin release, the 5-HT 2A/5-HT 2C receptor antagonist, ritanserin, was used. Under resting conditions, a dose of 5 mg/kg s.c. blocked the NMDA-induced prolactin release. In rats submitted to restraint, ritanserin decreased the prolactin response and NMDA was unable to correct the stress serum prolactin levels. The 5-HT 1A receptor agonist, 8-hidroxypropyl-amino tetralin (8-OH-DPAT) (3 mg/kg s.c.), increased basal serum prolactin levels and restored serum prolactin in stressed animals pretreated with CGS 19755 (5 mg/kg). The present data strongly suggest that the glutamatergic system participates in the regulation of prolactin secretion. A stimulation tone seems to be exerted via the tuberoinfundibular dopaminergic system, and the prolactin release evoked by restraint apparently involves glutamate/NMDA receptors linked to a serotoninergic pathway.

Effects of chronic hyperprolactinemia on tuberoinfundibular dopaminergic neurons.

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.

Chronic Hyperprolactinemia and Changes in Dopamine Neurons

The tuberoinfundibular dopaminergic (TIDA) system is known to inhibit prolactin (PRL) secretion. In young animals this system responds to acute elevations in serum PRL by increasing its activity. However, this responsiveness is lost in aging rats with chronically high serum PRL levels. The purpose of this study was to induce hyperprolactinemia in rats for extended periods of time and examine its effects on dopaminergic systems in the brain. Hyperprolactinemia was induced by treatment with haloperidol, a dopamine receptor antagonist, and Palkovits' microdissection technique in combination with high-performance liquid chromatography was used to measure neurotransmitter concentrations in several areas of the brain. After 6 months of hyperprolactinemia, dopamine (DA) concentrations in the median eminence (ME) increased by 84% over the control group. Nine months of hyperprolactinemia produced a 50% increase in DA concentrations in the ME over the control group. However, DA response was lost if a 9-month long haloperidol-induced hyperprolactinemia was followed by a 11 12 month-long extremely high increase in serum PRL levels produced by implantation of MMQ cells under the kidney capsule. There was no change in the levels of DA, norepinephrine (NE), serotonin (5-HT), or their metabolites in the arcuate nucleus (AN), medial preoptic area (MPA), caudate putamen (CP), substantia nigra (SN), and zona incerta (ZI), except for a decrease in 5-hydroxyindoleacetic acid (5-HIAA) in the AN after 6-months of hyperprolactinemia and an increase in DA concentrations in the AN after 9-months of hyperprolactinemia. These results demonstrate that hyperprolactinemia specifically affects TIDA neurons and these effects vary, depending on the duration and intensity of hyperprolactinemia. The age-related decrease in hypothalamic dopamine function may be associated with increases in PRL secretion.

Neurotensin and tyrosine hydroxylase in the tuberoinfundibular system of the guinea pig hypothalamus with special emphasis to lactation status.

Immunohistochemical methods allowed us to study the distribution of neurotensin immunoreactivity (NT-IR) in the infundibular area of the guinea pig and to obtain evidence of a clear increase of such immunoreactivity in females during lactation. By use of the double immunolabeling method we demonstrated the presence of NT in the tuberoinfundibular dopaminergic (TIDA) neuronal system, in the nerve terminals of the median eminence as well as in the arcuate perikarya. In addition, NT-IR was detected in anterior pituitary cells especially stained in the rostral part of the gland of lactating females. These cells were identified exclusively as gonadotrophs by use of the elution-restaining procedure. These results suggests that NT is able to participate in the modulation by TIDA of prolactin secretion. Moreover, NT production by gonadotrophs could be responsible for other unknown pituitary actions.

Exposure to a Short Photoperiod Increases Sensitivity to Dopamine Inhibition of Prolactin Release from Siberian Hamster Pituitary

Prolactin (PRL) secretion from the anterior pituitary is tonically controlled by the activity of the hypothalamic tuberoinfundibular dopaminergic (TIDA) system. Changes in TIDA activity have been associated with the decrease in basal PRL levels shown by hamsters exposed to a short-day photoperiod. Potential concurrent changes in the sensitivity of pituitary lactotropes to the inhibitory actions of dopamine on PRL release were investigated in tissue harvested from animals that had been preexposed to either a stimulatory, long-day 16-hour-light:8-hour-dark (16L:8D) photoperiod, or to a nonstimulatory, short-day (10L:14D) photoperiod for 8-10 weeks. Tissue was maintained in a perifusion tissue culture system and received a 1-hour pulse of varying concentrations of dopamine (DA) shortly after the equilibration period. Fractions of the media were collected every 1/2 h and PRL concentrations in each sample determined via radioimmunoassay. At the highest concentration of DA (10(-6) M), a highly significant inhibition of PRL levels was seen for both 16L and 10L pituitaries. At both mid range concentrations of DA (10(-7) and 10(-8) M), both tissue types showed a significant suppression of PRL, but the reduction was greater for tissue that had been obtained from 10L animals. At the lowest concentration of DA (10(-9) M), a significant suppression of PRL occurred for tissue harvested from 10L animals, but not for tissue taken from 16L animals. These results indicate that the responsiveness of anterior pituitary tissue to the inhibitory effects of DA are altered by photoperiod exposure, and this change is likely a consequence of changes in the characteristics of the D2 receptor population on pituitary lactotropes. Short-day-induced increases in sensitivity to the inhibitory effects of DA may be due to increases in receptor number, or to increased affinity of the D2 receptor for its ligand.

Dopaminergic control of prolactin secretion regulation (review of experimental and clinical trials)

Prolactin secretion (PRL) is under complex neuroendocrine control. in which factors of various nature are involved: neurotransmitters, biologically active neuropeptides, as well as hormones of peripheral endocrine glands. However, the dominant role belongs to dopamine, which is the most important of endogenous prolactin inhibiting substances. Convincing evidence of this was obtained after the discovery and study of the tuberoinfundibular dopaminergic system of the hypothalamus, which is a part of a complex neuroendocrine system for regulating the secretion of PRL.

Adrenergic innervation of dopamine neurons in the hypothalamic arcuate nucleus of the rat

Tuberoinfundibular dopaminergic (TIDA) neurons, which represent the final common pathway in the inhibitory neuronal control of prolactin (PRL) secretion, are regulated by synaptic input from various transmitter systems. Because adrenergic receptors at hypothalamic sites were implicated in the central regulation of lactotrophs, we hypothesized that a synaptic communication might exist between adrenergic pathways ascending from the brain stem and the TIDA system. Polyclonal antisera directed towards phenylethanolamine N-methyltransferase (PNMT) and tyrosine hydroxylase (TH), biosynthetic enzymes of catecholamines, were used for the simultaneous immunocytochemical detection of adrenergic fibers and TIDA neurons, respectively, in Vibratome sections of the rat hypothalamus. By the light microscopic evaluation of double-immunostained sections, PNMT-immunoreactive (IR) axon varicosities were localized in juxtaposition to TH-IR cell bodies and dendrites in the arcuate nucleus (AN) which contains perikarya and dendrites of TIDA neurons. The ultrastructural analysis of contacts provided firm evidence for the occurrence of synaptic interactions between the adrenergic and TIDA neuronal systems. These morphological findings show that adrenergic neurons are involved in the afferent regulation of the TIDA system and indicate a putative pathway of central adrenergic effects upon PRL secretion.

Galanin-containing axons synapse on tyrosine hydroxylase-immunoreactive neurons in the hypothalamic arcuate nucleus of the rat

Prolactin (PRL) secretion by the anterior pituitary gland is dependent upon the tonic inhibitory influence of the tuberoin-fundibular 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.

Plasticity in expression of immunoreactivity for neuropeptide Y, enkephalins and neurotensin in the hypothalamic tubero-infundibular dopaminergic system during lactation in mice.

In lactating nursing vs lactating pup-deprived mice, single or multiple immunolabeling was performed to compare immunoreactivities (ir) for neuropeptide Y (NPY), enkephalins (ENK) and neurotensin (NT) in the tyrosine hydroxylase (TH)-ir (ENK) and neurotensin (NT) in the tyrosine hydroxylase (TH)-ir hypothalamic tubero-infundibular dopaminergic (TIDA) system. NPY-, ENK- and NT-irs were intensely expressed and coexisted in virtually all TH-ir endings in the median eminence (ME) of nursing mice. Removal of the pups induced a marked depletion of the peptide-irs from the ME TH-ir endings. In the arcuate nucleus (ARC) of colchicine-treated nursing mice which received peripheral injections of Fluoro-Gold (FG) to retrogradely label neuroendocrine cells, virtually all dorsal A12 TH-ir perikarya simultaneously expressed, with individual variations, NPY-, ENK- and NT-irs, and all contained FG. These results suggest that the synthesis of NPY, ENK and NT is enhanced in TIDA neurons during lactation and that these neuromessengers may be co-released together with DA from the ME to regulate the suckling-induced prolactin secretion at the hypothalamic and/or pituitary levels.

Suppressed tyrosine hydroxylase gene expression in the tuberoinfundibular dopaminergic system during lactation

Suppressed tyrosine hydroxylase gene expression in the tuberoinfundibular dopaminergic system during lactation

Development of the tuberoinfundibular system in rats: birthdates of the tyrosine hydroxylase-immunopositive neurons

The present study has attempted to determine the birthdates of the tyrosine hydroxylase (TH)-immunopositive neurons in the arcuate nucleus (AN) of rats, thus evaluating the time of the last mitotic divisions of their cell precursors. For this aim, ‘long-survival’ [ 3H]thymidine autoradiography was used in combination with immunocytochemistry of TH, the first enzyme of catecholamine synthesis. According to our data, some TH-immunopositive neurons in the AN were born as early as the 13th fetal day. At day 14, the number of double-labeled neurons almost tripled while reaching a maximum at day 15 of the intrauterine development. The fraction of the double-labeled neurons dropped on the following day, and practically disappeared by fetal day 17, showing cessation of the production of the TH-immunopositive neurons. The birth of the TH-immunopositive neurons is considered as the onset of the development of the tuberoinfundibular dopaminergic system.