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Altered expression of neprilysin family members in the pituitary gland of sleep-disturbed rats, an animal model of severe fatigue.

Alterations of the expression of some peptidases in the pituitary gland of a fatigued rat model were identified. Rats were kept in a cage filled with water to a height of 1.5 cm to disturb deep sleep. After 24-h sleep disturbance, expression of neutral endopeptidase 24.11 (neprilysin) mRNA was increased in the intermediate lobe of the pituitary gland, whereas the mRNA expression of another family member, damage-induced neuronal endopeptidase, which is normally expressed in a subgroup of anterior pituitary cells, was significantly suppressed. These alterations were demonstrated by RT-PCR, northern blotting and in situ hybridization. Other family members, such as neprilysin 2 and endothelin converting enzyme-1, did not show any change in mRNA expression. An increase of neprilysin mRNA expression was not seen in any other tissues of the sleep-disturbed rats. The enzymatic activity of neprilysin was also increased in the pituitary. The augmentation of neprilysin expression and activity was prolonged as long as the sleep disturbance continued (up to 5 days), and returned to the basal level when rats were allowed to sleep freely. These results suggest that peptide processing and degradation in the pituitary may be an influential factor in fatigued states such as sleep disturbance.

Adrenocorticotropic Hormone↗

Ontogeny of the sensitizing effect of oestradiol and luteinizing hormone releasing hormone on the anterior pituitary gland of the female rat.

The ontogeny of the facilitatory effect of oestradiol and luteinizing hormone releasing hormone (LH-RH) on the responsiveness of the anterior pituitary gland to LH-RH has been studied in vitro using pituitary glands from female rats age 15, 17, 20, 31, 35 and 38 days. The facilitatory effect of oestradiol was already well established by day 15, while the facilitatory effect of LH-RH (priming effect) developed only after day 17. Although it increased the overall response of the gland to LH-RH, oestradiol did not selectively enhance the priming effect of LH-RH. Both the effect of oestradiol and LH-RH reached a peak on day 25, 7 days before vaginal opening in this colony, and, as assessed by measuring pituitary LH contents, were not dependent upon the synthesis of LH. These data show that different mechanisms may be involved in the facilitation of pituitary responsiveness by oestradiol and LH-RH, but that both mechanisms appear to depend more upon an increase in the sensitivity of the receptor/release apparatus rather than in the gonadotrophin content of the gonadotrophs.

Animals↗

p75-NGFR expression in the human prenatal pituitary gland.

The aim of this study was to elucidate the distribution of nerve growth factor receptor (NGFR) in the prenatal human pituitary gland until 21 weeks of gestation. Eight fetuses, with gestational ages from 13 to 21 weeks, were examined. The midaxial tissue block from the cranial base, including the pituitary gland and the sella turcica, was excised from the fetuses. The tissue was decalcified, embedded in paraffin, and cut in serial sections in 4-micro thicknesses. Immunohistochemistry was performed with monoclonal antibody p75-NGFR. p75-NGFR immunoreactivity was observed in fetuses from 15 weeks of gestation in the borderline between pars intermedia and the neurohypophysis.

Fetus↗

Transforming growth factor-alpha expression in the anterior pituitary gland: regulation by epidermal growth factor and phorbol ester in dispersed cells.

We have previously reported the immunohistochemical localization of transforming growth factor-alpha (TGF alpha) in the intact bovine anterior pituitary gland. Furthermore, we have purified TGF alpha from the conditioned medium of cell cultures derived from the bovine anterior pituitary. We report her the identification of the TGF alpha mRNA from both the intact bovine anterior pituitary gland and the anterior pituitary derived cell cultures. The level of TGF-alpha mRNA in the cell cultures is greater than that present in the intact gland. The TGF-alpha mRNA level increased when the cell cultures were allowed to incubate in their conditioned medium for 3 days, suggesting that a secretory product from the cultured cells is capable of stimulating the accumulation of the TGF-alpha mRNA. 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation of these cells resulted in a 6-fold increase in the level of TGF-alpha secreted into the conditioned medium. TPA appears to stimulate TGF-alpha secretion at the level of gene transcription as TPA treatment also resulted in an increased accumulation of the TGF-alpha mRNA. The epidermal growth factor (EGF) receptor mRNA was examined in these cell cultures and it increased with TPA treatment in an analogous manner to the TGF-alpha mRNA. EGF treatment of the pituitary cells resulted in an increased level of TGF-alpha mRNA which followed the same time course as TPA, maximal stimulation occurred after 8 h of treatment. The magnitude of EGF stimulated TGF-alpha mRNA was not as great as that seen by TPA stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regulation of growth hormone expression in fetal rat pituitary gland by thyroid or glucocorticoid hormone.

The regulation of growth hormone (GH) cell development by thyroid and glucocorticoid hormones in the fetal rat pituitary gland was examined. Dexamethasone (Dex) treatment of dams induced GH and GH mRNA accumulation in the fetal pituitary gland on day 17 or 18 of gestation when substantial GH expression has not yet occurred in the control fetus. The additional thyroxine injections apparently enhanced the effect of Dex, whereas it exhibited no effect when given alone. The reduction of fetal thyroid hormone level by methimazole suppressed either the Dex induction of GH expression on day 18 or the spontaneous onset of GH expression on day 19 of gestation. The results suggest that 1) thyroid hormone exerts its stimulatory action on fetal GH gene expression only in the presence of glucocorticoid, 2) this synergistic action of these two hormones is evident as early as day 17 of gestation, and 3) rapid maturation of GH cells seen on day 19 in the normal fetus is considered to be induced by concomitant increase in both serum thyroid and glucocorticoid hormone levels.

Animals↗

Effects of estrogens on the characteristics of [3H]spiroperidol and [3H]RU24213 binding in rat anterior pituitary gland and brain.

Since estrogens have been found to exert a marked inhibitory effect on dopaminergic action at the anterior pituitary and striatal levels in the rat, the effect of estrogen treatment has been studied on the binding characteristics of the dopamine (DA) antagonist [3H]spiroperidol and of the new DA agonist [3H]N-n-propyl-N-phenylethyl-beta-(3-hydroxyphenyl)ethylamine hydrochloride ([3H]RU24213) in rat striatum, nucleus accumbens + olfactory tubercle, frontal cortex and anterior pituitary gland. Specificity of binding was carefully examined in order to investigate possible changes of the agonist and antagonist states of the DA receptor. Estrogen treatment led to a small increase (approx. 20%) of [3H]spiroperidol and [3H]RU24213 binding in rat striatum, nucleus accumbens + olfactory tubercle and frontal cortex while no significant effect was found in the anterior pituitary gland. That the increased binding is due to a corresponding increased number of binding sites and not to higher affinity is indicated by the absence of effect of estrogen treatment on the IC50 values for displacement of the two labeled ligands by a variety of unlabeled compounds. Specificity of binding of DA agonists and antagonists remained unchanged after estrogen treatment. The present data suggest that the potent desensitizing effect of estrogen on DA action at the striatal and pituitary levels is exerted at a step subsequent to binding of DA to its receptor.

Animals↗

Hypothalamic control of prolactin and growth hormone secretion in the pituitary gland of the pigeon and the chicken: in vitro studies.

Hypothalamic extracts stimulated the release of prolactin and growth hormone from pigeon and chicken pituitary glands incubated in vitro. Release of hormone was proportional to the amount of hypothalamic extract added. Pituitary glands from "lactating" pigeons released more prolactin and their hypothalami contained more prolactin-releasing activity compared with controls. Partial separation of prolactin releasing activity from growth hormone releasing activity in chicken hypothalamic extract was achieved using gel filtration chromatography. Co-incubation studies in vitro with hypothalamic tissue present showed that prolactin release from the pituitary was inhibited and growth hormone release was stimulated when dopamine was added to the medium. The effects of dopamine were blocked by the antagonist pimozide. The possible existence of hypothalamic releasing and inhibiting factors regulating secretion of prolactin and growth hormone is discussed.

Animals↗

Distribution of brain-derived neurotrophic factor in the rat pituitary gland.

Immunohistochemical techniques were used to determine the distribution of brain-derived neurotrophic factor (BDNF) in the adult rat pituitary gland. In the posterior lobe, BDNF staining was found only within fibers. Within the intermediate lobe, nearly all cells were labeled intensely for BDNF. In the anterior lobe, varying degrees of BDNF immunoreactivity were observed exclusively in cells shown by double-labeling techniques to contain thyroid stimulating hormone (TSH), although not all TSH-positive cells contained detectable BDNF labeling. These results are consistent with and extend information from previous studies demonstrating BDNF expression in the pituitary gland and further support the idea that this neurotrophin plays a role in endocrine function.

Animals↗

Image-guided endonasal transsphenoidal microsurgical treatment of recurrent microadenomas of the pituitary gland.

BACKGROUND: Neuronavigation is a commonly used technology that provides continuous, three-dimensional information for the precise localization of and surgical trajectory to brain lesions. This study was performed to evaluate the role that navigation can play in assisting microsurgical transsphenoidal surgery for precise localization and removal of recurrent pituitary tumours while simultaneously preserving pituitary gland function. METHOD: During a 6-month period -- July 2004 until December 2004 -- 9 patients with recurrent pituitary tumours (5 female and 4-male) were treated with navigation-guided transsphenoidal microsurgical resection. Surgery was performed via a paraseptal or endonasal transsphenoidal approach. The navigation system Vector Vision (Brain Lab, Heimstetten, Germany) allowed precise localization of the tumours (7 hormonal active and 2 inactive microadenomas) in respect to the pituitary gland, the carotid arteries and the cavernous sinus. RESULTS: Postoperative MRI investigations of the 9 patients treated with image-guided transsphenoidal microsurgery, showed total tumour removal in 7 (77 %) patients and subtotal removal in 2 patients (23 %). One patient (11 %) developed a cerebral spinal fluid (CSF) leak and was treated conservatively. One patient (11 %) had preoperative insufficiency of the corticotrope axis which remained unchanged postoperatively. Of the remaining 8 patients who did not have preoperative endocrinological disturbance, only one (12 %) developed postoperative insufficiency of the corticotrope axis. Out of the 7 patients with hormone active tumours, 5 (72 %) patients showed no more postoperative hormonal activity. CONCLUSION: Microneurosurgical transsphenoidal techniques combined with image-guided systems can precisely define the localization and removal of lesions in the sella region with respect to the margins of important anatomical structures in the neighbourhood and the endocrinological functionality of the pituitary gland.

Adenoma↗

Normal pituitary gland: coronal MR imaging of infundibular tilt.

To determine the prevalence of pituitary infundibular deviation or tilt as a normal variant, coronal magnetic resonance (MR) images of 50 patients who had been examined for reasons other than pituitary disease were evaluated retrospectively. Forty-six percent of the patients had a more or less pronounced tilt of the pituitary stalk. This tilt was due to developmental lateral eccentricity of the pituitary gland in relationship to the midline of the brain in 34% and to ontogenic eccentric insertion of the pituitary infundibulum off the midline of the gland in the other 12%. This high frequency of stalk deviation in patients without pituitary disease suggests that such displacement by itself should not be used to support the presence of pituitary microadenoma on MR images or computed tomograms.

Adenoma↗

Different processing of chromogranin B into GAWK-immunoreactive fragments in the bovine adrenal medulla and pituitary gland.

Chromogranin B 420-493 (GAWK)-like immunoreactivity (chromogranin B (420-493)-LI) was determined by radioimmunoassay using two different rabbit antisera, one raised against chromogranin B (420-436) (GAWK 1-17) (Ab420-436) and the other against chromogranin B 439-457 (GAWK 20-38) (Ab439-457), in bovine and human tissues. Chromogranin B (420-493)-LI was present in the bovine adrenal medulla chromaffin granules as well as in the anterior pituitary gland and was released from the cultured bovine chromaffin cells by stimulation with high K+ or nicotine. Chromogranin B (420-493)-LI present in the bovine tissues was detected using Ab420-436 but was not detected using Ab439-457. In the human tissues, chromogranin B (420-493)-LI was detected using Ab420-436 as well as Ab439-457. This suggests that the amino acid sequence of this region (chromogranin B 439-457) is different between human and bovine. On the gel permeation chromatography, chromogranin B (420-493)-LI was eluted at the void volume in the bovine adrenal medulla and at an apparent molecular weight of 4000 in the anterior pituitary gland. On the reverse-phase high-performance liquid chromatography, multiple peaks of chromogranin B (420-493)-LI was detected in the bovine adrenal medulla while one component of chromogranin B (420-493)-LI was found in the anterior pituitary gland. These results suggest that chromogranin B is processed into small fragments of chromogranin B (420-493)-LIs and that this processing is tissue-specific.

Adrenal Medulla↗

CRF stimulates adenylate cyclase activity in the intermediate lobe of the pituitary gland.

Ovine corticotropin-releasing factor (CRF) stimulates adenylate cyclase activity in homogenate of the intermediate lobe of the bovine pituitary gland at an ED50 value of 150 nM. GTP increases the stimulatory effect induced by CRF as well as by the beta-adrenergic agonist isoproterenol on [32P]cyclic AMP formation in rat pars intermedia homogenate. In addition, GTP is required for inhibition by dopamine of the stimulatory action of both CRF and isoproterenol. The present data show that CRF stimulates adenylate cyclase activity in the intermediate lobe of the pituitary gland at least partly through a GTP-dependent mechanism. Moreover, dopamine can interfere with the action of CRF as well as that of isoproterenol, thus indicating that the neurohormone could be involved, in addition to beta-adrenergic agents, as stimulator of pars intermedia cell activity.

Adenylyl Cyclases↗

Cell proliferation in the rat pituitary gland: a mechanism of control in prolactin cells.

We investigated the relationship between prolactin content and DNA replication in the anterior pituitary gland. Thymidine incorporation in pregnant rats is significantly lower than in virgin controls. This is accompanied by a decreased activity of DNA polymerase. Sulpiride administration to pregnant rats enhances thymidine incorporation to levels similar to virgin controls. The results indicate a negative feedback between prolactin content and DNA synthesis in the rat anterior pituitary gland.

Animals↗