Case Report: Lipoma of the Tuber Cinereum Mimicking a Pituitary Gland Abnormality in a Girl With Central Precocious Puberty.

Introduction: Magnetic Resonance Imaging (MRI) is the best approach to investigate the hypothalamic-pituitary region in children with central precocious puberty (CPP). Routine scanning is controversial in girls aged 6-8 year, due to the overwhelming prevalence of idiopathic forms and unrelated incidentalomas. Cerebral lipomas are rare and accidental findings, not usually expected in CPP. We report a girl with CPP and an unusually shaped posterior pituitary gland on SE-T1w sequences. Case Description: A 7.3-year-old female was referred for breast development started at age 7. Her past medical history and physical examination were unremarkable, apart from the Tanner stage 2 breast. X-ray of the left-hand revealed a bone age 2-years ahead of her chronological age, projecting her adult height prognosis below the mid parental height. LHRH test and pelvic ultrasound were suggestive for CPP. Routine brain MRI sequences, SE T1w and TSE T2w, showed the posterior pituitary bright spot increased in size and stretched upward. The finding was considered as an anatomical variant, in an otherwise normal brain imaging. Patient was started on treatment with GnRH analogue. At a thorough revaluation, imaging overlap with adipose tissue was suspected and a new MRI scan with 3D-fat-suppression T1w-VIBE sequences demonstrated a lipoma of the tuber cinereum, bordering a perfectly normal neurohypophysis. 3D-T2w-SPACE sequences, acquired at first MRI scan, would have provided a more correct interpretation if rightly considered. Conclusion: This is the first evidence, to our knowledge, of a cerebral lipoma mimicking pituitary gland abnormalities. Our experience highlights the importance of considering suprasellar lipomas in the MRI investigation of children with CPP, despite their rarity, should the T1w sequences show an unexpected pituitary shape. 3D-T2w SPACE sequences could be integrated into standard ones, especially when performing MRI routinely, to avoid potential misinterpretations.

Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats.

Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia. We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia. Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (10(10) pfu) of either an adenoviral vector expressing the gene for beta-galactosidase; (Y-betagal and S-betagal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF, respectively). Transgenic GDNF levels in supernatants of GDNF adenovector-transduced N2a neuronal cell cultures were 25+/-4 ng/ml, as determined by bioassay. In the rats, serum prolactin (PRL) was measured at regular intervals. On day 17 animals were sacrificed and neuronal nuclear antigen (NeuN) and tyrosine hydroxylase (TH) immunoreactive cells counted in the arcuate-periventricular hypothalamic region. The S-GDNF but not the S-betagal rats, showed a significant reduction in body weight. The chronic hyperprolactinemia of the senile females was significantly ameliorated in the S-GDNF rats (P<0.05) but not in the S-betagal rats. Neither age nor GDNF induced significant changes in the number of NeuN and TH neurons. We conclude that transgenic GDNF ameliorates chronic hyperprolactinemia in aging female rats, probably by restoring TIDA neuron function.

Dopamine and 7-OH-DPAT may act on D(3) receptors to inhibit tuberoinfundibular dopaminergic neurons.

Whether the tuberoinfundibular dopaminergic (TIDA) neurons resided in the dorsomedial arcuate nucleus (dmARN) can respond to dopamine and a dopamine D(3) receptor agonist, 7-hydroxydipropylaminotetralin (7-OH-DPAT), was the focus of this study. In studies using extracellular single-unit recording of dmARN neurons in brain slices obtained from ovariectomized rats, dopamine and 7-OH-DPAT inhibited 60.1% (n = 141) and 80.9% (n = 47) of recorded dmARN neurons, respectively. Other dopamine D(1) or D(2) receptor agonists were not as effective. Intracerebroventricular injection of 7-OH-DPAT (10(-9) mol/3 microl) in ovariectomized, estrogen-primed rats significantly lowered the TIDA neuronal activity as determined by 3, 4-dihydroxyphenylacetic acid (DOPAC) levels in the median eminence. Co-administration of a putative D(3) receptor antagonist, U-99194A, could prevent the effect of 7-OH-DPAT. Unilateral microinjection of 7-OH-DPAT or dopamine itself (10(-11)-10(-9) mol/0.2 microl) into the right dmARN exhibited the same inhibitory effect on TIDA neurons. In all, dopamine may act on D(3) receptors to exhibit an inhibitory effect on its own release from the TIDA neurons.

Circadian changes of serum prolactin levels and tuberoinfundibular dopaminergic neuron activities in ovariectomized rats treated with or without estrogen: the role of the suprachiasmatic nuclei.

Variations of serum prolactin (PRL) levels and activities of tuberoinfundibular dopaminergic (TIDA) neurons during the afternoon of ovariectomized (OVX) rats treated with or without estrogen were determined in this study. Long-term OVX rats treated with or without polyestradiol phosphate (0.1 mg/rat, s.c.) were decapitated every hour from 10.00 to 19.00 h (except 11.00 and 13.00 h). Serum PRL and median eminence (ME) dihydroxyphenylacetic acid (DOPAC) or dihydroxyphenylalanine (DOPA) levels were determined by radioimmunoassay and high performance liquid chromatography plus electrochemical detection, respectively. A prominent PRL surge started and peaked around 14.00-15.00 h, and remained significantly higher than levels of 10.00 and 12.00 h throughout the afternoon. Significant decreases of ME DOPAC and DOPA concentrations were also observed between 14.00 and 19.00 h. In OVX rats with no estrogen replacement, no PRL surge was observed and the changes of ME DOPAC concentrations during the afternoon were not significant except for that at 17.00 h. The ME DOPA accumulation, however, exhibited significantly lower levels from 14.00 to 19.00 h than that at 12.00 h, indicating that an endogenous rhythm for DA synthesis existed in OVX rats. In estrogen-treated OVX rats bearing bilateral lesions of the suprachiasmatic nuclei, both changes in serum PRL level and TIDA neuron activity were abolished. We conclude that an endogenous rhythm of the activities of TIDA neurons may exist in both OVX and OVX plus estrogen-treated rats. The rhythm is regulated by the suprachiasmatic nuclei and may be amplified by estrogen for the induction of PRL surge.

Neuroendocrine regulation of thyrotropin-releasing hormone (TRH) in the tuberoinfundibular system.

[...] It is now required to list each part needed for mucous excretion. They are two ducts in the brain substance, then a thin portion of membrane shaped as the infundibulum, then the gland that receives the tip of this infundibulum and the ducts that drive the mucus (pituita) from this gland to the palate and nares. [...] and I said that one (duct) [...] from the middle of the common cavity (third ventricle) descends [...] into the brain substance, and the end of this duct is [...] the sinus of the gland where the brain mucus is collected [...].

Short-term treatment with 17-beta estradiol enhances spontaneous [3H] dopamine release from cultured rat tuberoinfundibular neurons.

The effects of 17-beta estradiol (E2) on spontaneous [3H] dopamine ([3H]DA) release was investigated using primary cultured cells from the tuberoinfundibular region of rat hypothalamus, which includes DA neurons. [3H] DA uptake by the neurons in the presence of E2 at 10(-8) mol/l was similar to that by control cells. Pretreatment with E2 at 10(-9) mol/l or more resulted in dose-dependent increase in spontaneous [3H] DA release from the cultured hypothalamic cells. The spontaneous [3H] DA release reached almost a plateau on pretreatment with E2 at 10(-9) mol/l for 6 hours. Pretreatment with 1 nM E2 also enhanced DA release induced by 10 microM ionophore A23187. These results indicate that estrogen stimulates tuberoinfundibular DA neuronal activity.

Changes in tuberoinfundibular dopaminergic neuron activity during the rat estrous cycle in relation to the prolactin surge: alteration by a mammary carcinogen.

An attempt was made to correlate the physiological or the dimethylbenz(a)anthracene (DMBA)-enhanced serum prolactin (PRL) surge, which occurs in the afternoon of proestrus in female Sprague-Dawley (SD) rats, with physiological or pathological changes in two biochemical estimates of the tuberoinfundibular dopaminergic (TIDA) neuron activity. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) concentrations as well as tyrosine hydroxylase (TH) activity were measured in the median eminence (ME) of control or DMBA-pretreated SD rats throughout the estrous cycle in relation to PRL secretion. In both groups of females, while the DA content was fairly constant, the DOPAC content and TH activity in the ME fluctuated markedly throughout the estrous cycle. Thus, in control animals, the DOPAC content, DOPAC/DA ratio and TH activity which were stable on the days of diestrus and morning of proestrus were markedly decreased at noon and early afternoon when serum PRL levels began to rise. Later in the afternoon of proestrus, when serum PRL levels were maximal, there was a marked but transient increase in the DOPAC content and DOPAC/DA ratio as well as a brief surge in TH activity. In the evening of the same day, when serum PRL returned to basal levels, the DOPAC content, DOPAC/DA ratio and TH activity were low. Finally on estrus morning, the DOPAC content, DOPAC/DA ratio and TH activity increased again to reach the diestrus levels. In DMBA-pretreated females, similar fluctuations in TIDA neuronal activity occurred during the estrous cycle, but the dynamics of these changes was altered: the DOPAC/DA ratio and TH activity first showed a marked increase in the morning of proestrus day, before decreasing dramatically.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrical stimulation of the arcuate nucleus increases the metabolism of dopamine in terminals of tuberoinfundibular neurons in the median eminence.

The purpose of the present study was to examine the effects of procedures that alter impulse flow in tuberoinfundibular dopamine (DA) neurons on the metabolism of DA in the median eminence and on the secretion of prolactin from the anterior pituitary. Twenty min following the administration of gamma-butyrolactone (GBL, 1000 mg/kg, i.p.) there was a marked decrease in 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations in the median eminence and an increase in prolactin concentrations in the serum, indicating that a decrease in activity of tuberoinfundibular DA neurons is accompanied by a decrease in DA metabolism in the median eminence and a loss of tonic inhibition of pituitary prolactin secretion. Activation of tuberoinfundibular DA neurons by bilateral stimulation of the arcuate nucleus in GBL-treated rats produced a rapid increase in median eminence DOPAC concentrations and a time-dependent decrease in serum prolactin concentrations. Nomifensine (25 mg/kg, i.p., 30 min), a DA uptake inhibitor, had no effect on median eminence DOPAC concentrations in sham- or arcuate nucleus-stimulated rats, indicating that regardless of the level of activity of tuberoinfundibular neurons, very little DA is recaptured and metabolized in terminals of these neurons in the median eminence. Taken together these results reveal that alterations in impulse flow in tuberoinfundibular DA neurons are accompanied by corresponding changes in the metabolism of DA in the median eminence.

Direct inhibitory effect of long term estradiol treatment on dopamine synthesis in tuberoinfundibular dopaminergic neurons: in vitro studies using hypothalamic slices.

The mechanism of the inhibitory effect of long term treatment with estradiol on dopamine synthesis in tuberoinfundibular dopaminergic (TIDA) neurons was studied by using hypothalamic slices from ovariectomized rats. Treatment with 2 mg estradiol valerate (EV) at a 3-week interval increased the weight of the anterior pituitary gland and the concentration of serum PRL. In vivo and in vitro dopamine synthesis in TIDA neurons were estimated in EV-treated animals by 3,4-dihydroxyphenylalanine (DOPA) accumulation in the median eminence after injections of 3-hydroxybenzylhydrazine (NSD 1015), a DOPA decarboxylase inhibitor, and after incubation of hypothalamic slices with NSD 1015, respectively. In vivo DOPA accumulation in the median eminence was less in EV-treated rats than in control rats. The basal rate of in vitro DOPA accumulation in the median eminence of hypothalamic slices from EV-treated rats was lower than that in control rats. Ca2+-dependent DOPA accumulation in the median eminence, determined by incubation in medium containing depolarization agents such as 50 mM K+ and veratridine, was decreased in EV-treated rats. Furthermore, cAMP-dependent DOPA accumulation, determined by incubation with Bu2cAMP or forskolin, was also suppressed in EV-treated rats. The decreased depolarization-induced DOPA accumulation in the median eminence recovered after cessation of EV treatment. Hyperprolactinemia lasting for 6 weeks, achieved by transplantation of anterior pituitaries under the kidney capsule, increased the rate of depolarization-induced DOPA accumulation in the median eminence. On the other hand, EV treatment was effective in inhibiting depolarization-induced DOPA accumulation in hypophysectomized rats regardless of the presence of anterior pituitary transplants. These results suggest that chronically administered estradiol inhibits dopamine synthesis in TIDA neurons via a direct action on the hypothalamus and overcomes the facilitatory action of PRL on dopamine synthesis; and estradiol inhibits all three distinct systems that regulate basal, Ca2+-dependent, and cAMP-dependent dopamine synthesis in TIDA neurons.

Responsiveness of tuberoinfundibular dopamine neurons in the aged female rat to the stimulatory actions of prolactin.

The autoregulatory feedback control of prolactin, which is mediated by tuberoinfundibular dopamine (DA) neurons, is altered in the aged rat; this is evidenced by increased circulating concentrations of prolactin and decreased activity of these neurons. In the present study the action of prolactin on tuberoinfundibular DA neurons in young and aged female rats was estimated by measuring the rate of DA synthesis (dopa accumulation following the administration of a decarboxylase inhibitor) in the median eminence. The rate of dopa accumulation in the median eminence of the aged (26 months) rat was reduced to 50-60% of that in the young (3 months) rat. The acute systemic administration of haloperidol, a DA antagonist which increases serum concentrations of prolactin or intracerebroventricular infusions of prolactin increased the rate of dopa accumulation in the median eminence of both young and aged rats by the same relative amount. The administration of haloperidol and prolactin increased the rate of DA synthesis to a greater extent in young than in aged rats. The administration of bromocriptine, a DA agonist which reduces serum concentrations of prolactin, decreased the rate of dopa accumulation in the median eminence of both young and aged rats. In young animals the intracerebroventricular administration of prolactin reversed the bromocriptine-induced decrease in DA synthesis in the median eminence after 4 h and caused a further increase after 12 h. Qualitatively similar effects were seen in the aged rats; however, prolactin-treated young rats had much higher levels of DA synthesis than aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute restraint stress decreases tuberoinfundibular dopaminergic neuronal activity: evidence for a differential response in male versus female rats.

The basal activity o f tuberoinfundibular dopaminergic (TIDA) neurons is higher and the response of these neurons to the stimulatory actions of prolactin is greater in the female than in the male rat. In the female rat, the restraint-stress-induced increase in serum prolactin concentrations is accompanied by a concurrent decrease in the activity of TIDA neurons. The purpose of the present study was to compare these effects of restraint in male and female rats. TIDA neuronal activity was estimated by measuring the rate of dopamine (DA) synthesis (DOPA accumulation after the administration of a decarboxylase inhibitor, NSD 1015) and the rate of DA turnover (decline of DA after administration of a tyrosine hydroxylase inhibitor; alpha-methyltyrosine) in the median eminence. Thirty minutes of restraint increased serum prolactin concentrations in both male and female rats, but a greater response was observed in the females. Restraint also decreased the rates of synthesis and turnover of DA in the median eminence of the female but not the male rat. The difference in the response of TIDA neurons in male and female rats to restraint is not the consequence of neuronal differentiation resulting from neonatal androgen exposure, because restraint aso decreased the activity of TIDA neurons in androgen-sterilized female rats. The inability of restraint stress to reduce TIDA neuronal activity in the male rat appears to be the consequence of testosterone, since TIDA neurons were responsive to restraint following castration of the males.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurochemical studies on central dopamine neurons--regional characterization of dopamine turnover.

A simple and rapid dissection procedure was adopted to sample representative areas of the main meso-telencephalic dopaminergic (DA) neuron systems (nigrostriatal and meso-limbic-cortical) in the rat CNS. The object was to explore nerve terminal fields, cell body groups and dendrites, and to investigate the DA utilization rates in these regions. DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) as well as noradrenaline (NA) were determined by liquid chromatography with electrochemical detection. Selective NA denervation with the neurotoxin DSP4 did not significantly change the DA levels in any of the regions studied, showing that the main part of the DA analysed originated from DA neurons. Administration of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (H44/68) resulted in a time-dependent, often multi-phasic, DA and NA depletion pattern that varied between different regions. Comparison between the rate of DA decline and DOPAC/DA or HVA/DA ratios (also indices for DA utilization) in the various regions showed that the initial rate of DA disappearance after H44/68 appeared to be the most relevant index of DA utilization. The most rapid initial DA decline after H44/68 was found in the cortical regions (frontal, cingulate, and entorhinal) and the cell body areas A9 and A10, in particular in the cingulate cortex (t1/2 approximately equal to 20 min), indicating a very rapid DA turnover in this region. DA disappearance was clearly slower in striatum (t1/2 approximately equal to 45 min) and the slowest rates were found in the olfactory tubercle and the nucleus accumbens (t1/2 approximately equal to 1.5-2 h). The DA disappearance (t1/2 approximately equal to 45 min) pattern in the dendritic area (substantia nigra, pars reticulata) suggested an axon-terminal like behaviour of the DA dendrites with respect to DA utilization. In general, the DA metabolite/DA ratios obtained for the various regions agreed closely with these results. The rate of NA disappearance after H44/68 was slower than that of DA in most regions. The most rapid NA decline was found in the cortical regions (t1/2 approximately equal to 1-2 h), while very slow in the A9 and A10 regions (t1/2 approximately equal to 3-5 h).

ACTH release after tuberal electrical stimulation in rats with various cuts around the medial basal hypothalamus.

After the combined treatment with dexamethasone, morphine and pentobarbitone, the electrical stimulation in the rat tuber cinereum induces a rise in plasma corticosterone (CS) level, probably by direct stimulation of the corticoliberin-producing neural elements and the consecutive ACTH release. We have attempted to locate these corticoliberin-containing neural elements by electrical stimulation in rats with various surgical cuts (deafferentations) around the medial basal hypothalamus (MBH). Seven to eight days after the complete circumsection of the MBH, the electrical stimulation of the isolated region did not affect plasma CS level. Also, the electrical excitation proved to be ineffective after antero-lateral or only lateral sections that interrupted the fibers running through the lateral region of the retrochiasmatic area. In contrast, a rise in CS level followed electrical stimulation of rats with anterolateral transections, provided the basal part of the lateral retrochiasmatic area stayed intact. We suggest that fibers traversing the basal region of the lateral retrochiasmatic area have a major role in the release of corticoliberin from the median eminence (ME).

[Immunocytological localization of peptide analogs of alpha-endorphin in several neurons of the lateral nucleus tuberis of Carassius auratus L. and Cyprinus carpio L]. / Localisation immunocytologique de peptides analogues à l'alpha-endorphine dans certains neurones du noyau latéral du tuber de Carassius.

Neurons of the pars lateralis of the N.L.T. of Carassius auratus and Cyprinus carpio display a positive immunocytological reaction with an anti alpha-endorphin serum. It is assumed that the peptides produced by these neurons are similar, if not identical, with alpha-endorphin, but their morphinomimetic properties have still to be established. Peptides of this kind may participate in the regulation of pituitary functions.

Catecholamine distribution in feline hypothalamus.

Catecholamine distribution was examined in cat hypothalamus using the histochemical fluorescence technique of Falck and Hillarp. The heaviest accumulations of catecholamine-containing varicosities were seen within the: anterior periventricular nucleus; dorsal hypothalamic area; bed nucleus of the inferior thalamic peduncle; doral component of the paraventricular nucleus; dorsomedial nucleus; infundibular nucleus; bed nucleus of the stria terminalis-medial division; and supraoptic nucelus. Catecholaminergic perikarya were observed within periventricular, dorsal, and caudal hypothalamic areas as well as within the supramamillary nucleus and caudal diencephalon. Catecholamine distribution in cat hypothalamus possesses both similarities and dissimilarities in relation to distributions reported in other mammals.