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Are mu-opioid receptors involved in the control of endothelin-1 release from the pituitary gland in normal and dehydrated rats?

UNLABELLED: The objective of the present study was to investigate whether the endogenous opioids are involved in the control of endothelin-1 release from the pituitary gland. To test this hypothesis we have measured the peripheral plasma concentration of ET-1 as well as the content of immunoreactive ET-1 (irET-1) in the pituitary in response to opioid receptors blockade in euhydrated and 24 h water-deprived Wistar-Kyoto rats. Placebo or naltrexone (50 micrograms/kg body wt.) were given i.v. in both groups. Trunk blood was collected to determine hematocrit, plasma sodium and ET-1 levels (RIA). Immunostaining of ET-1 in the whole pituitary glands was performed by colloidal gold labeling. The quantitative analysis of irET-1 was carried out under a light microscope using a computerized image analyzer (MultiScan). RESULTS: (1) Twenty-four-hour dehydration resulted in marked increase of peripheral concentration of ET-1. Naltrexone injection induced a significant elevation of ET-1 plasma concentration in both, dehydrated and control animals. (2) The content of irET-1 in anterior and intermediate lobes of the pituitary in dehydrated rats was markedly higher than in control group. (3) Naltrexone injection caused a rapid and significant reduction irET-1 within the anterior, intermediate and posterior lobes in dehydrated and control animals. CONCLUSIONS: (1) An elevation of irET-1 in the pituitary gland and peripheral circulation in dehydrated animals may play a role in maintaining of water-electrolyte balance. (2) The mu-opioid system appears to control the ET-1 release from the pituitary in normal and dehydrated animals.

Animals↗

Double tumors of anterior and posterior pituitary gland.

Double tumors were found in the anterior and posterior lobes of pituitary gland at autopsy in a patient who presented with progressive deterioration of mental status. The chromophobe adenoma of anterior lobe consisted of a mixture of non-immunoreactive hormone containing cells and a few prolactin (PRL) and growth hormone (GH) cells in the mid portion whereas the periphery of the tumor contained immunoreactive cells for PRL, GH, thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). A microscopic focus of granular cell myoblastoma (GCM) was found in the posterior lobe. Differentiation of tumor cells into anterior pituitary cells and GCM is discussed.

Adenoma, Chromophobe↗

Characterisation of two serine protease inhibitors expressed in the pituitary gland.

Serine protease inhibitors (serpins) are a family of structurally related proteins that play key roles in the regulation of proteolytic homeostasis. We have isolated a novel intracellular serpin, termed raPIT5a, from the rat pituitary gland. Northern blot analysis indicated raPIT5a mRNA expression in a range of tissues, including the adrenal gland and the brain. In situ hybridisation histochemistry revealed raPIT5a mRNA expression in specific cell populations in the rat pituitary gland, adrenal gland, and pancreas. Based on sequence similarities to other intracellular serpins, we predicted raPIT5a may inhibit the pro-apoptotic serine protease granzyme B. We confirmed this experimentally by identification of a stable inhibitory complex between granzyme B and raPIT5a. To determine whether granzyme B or granzyme B-related enzymes were expressed in the rat pituitary gland, we performed PCR using primers predicted to amplify granzyme B and two other published granzyme sequences. We identified rat natural killer protease-1 (RNKP-1), the rat homologue of granzyme B, and a novel putative serine protease highly similar to granzyme-like protein III (GLP III), which we termed GLP IIIa. These data suggest raPIT5a may regulate apoptosis in the pituitary by inhibition of granzyme B or GLP IIIa, or members of the caspase enzyme family which have similar substrate specificity. We have also identified expression of a second serpin, called neuroserpin, in pituitary tissue and found that it alters the morphology of the AtT20 corticotrope cell line, presumably through changes in cell adhesion. These results identify new roles for serpins in pituitary cell function.

Amino Acid Sequence↗

Structure and ultrastructure of the pituitary gland in the sea lamprey, Petromyzon marinus at different stages in its life cycle.

The structure and fine structure of the pituitary gland in the sea lamprey, Petromyzon marinus L., are described at all major stages in the life cycle. Synthetically active adenohypophysial cells are evident in even the smallest ammocoetes examined (body length 2.5 cm). An attempt is made to correlate changes in the activity of pituitary cell types with biological events. In the neurohypophysis a single fibre type was discriminated in electron micrographs. This contained electron-dense cytoplasmic granules 800 to 1600 A in diameter.

Age Factors↗

Modulation of beta-adrenergic receptors in the pituitary gland following adrenalectomy in rats.

The effects of adrenalectomy on beta-adrenergic receptors in the rat pituitary were examined using quantitative in vitro autoradiography with 125I-iodocyanopindolol (125ICYP). 125ICYP binding in the anterior, intermediate and posterior lobes of the pituitary gland was significantly increased in chronically adrenalectomized rats. The increase in 125ICYP binding sites in the rat pituitary following adrenalectomy was not reversed by glucocorticoid replacement with dexamethasone. These data indicate that catecholamines of adrenomedullary origin are capable of modulating beta-adrenergic receptors in the pituitary gland and suggest that peripheral epinephrine may be important in regulating pituitary hormone secretion.

Adrenalectomy↗

Determination of the source of 5-hydroxytryptaminergic neuronal projections to the neural and intermediate lobes of the rat pituitary gland through the use of electrical stimulation and lesioning experiments.

5-Hydroxytryptamine (5-HT)-containing axons and terminals have been visualized in the neural and intermediate lobes of the rat pituitary gland, but the origin of these fibers remains in question. This study was designed to determine if 5-HT cell bodies in the brainstem or in the dorsomedial nucleus of the hypothalamus project to either of these pituitary lobes. Since lesions and electrical stimulation of 5-HT cell bodies decrease and increase, respectively, the rate of 5-HT synthesis in regions innervated by these cells, these techniques were employed. The in vivo rate of 5-HT synthesis was determined by quantifying the rate of accumulation of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), in the neural and intermediate lobes of the pituitary gland 30 min after the administration of a decarboxylase inhibitor (NSD 1015, 100 mg/kg, i.p.). The application of 30 min of stimulating current (monophasic cathodal pulses of 1 ms duration and 0.3 mA current delivered at a frequency of 10 Hz) to electrodes implanted in the dorsal and median raphe nuclei increased the rate of 5-HT synthesis in both the neural and intermediate lobes of the pituitary gland. 5,7-Dihydroxytryptamine lesions of these nuclei altered neither 5-HTP accumulation nor 5-HT concentrations in the neural and intermediate lobes, but similar lesions of the nuclei raphe pontis and raphe magnus decreased both the concentration of 5-HT and the accumulation of 5-HTP in these pituitary regions.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

Vagotomy does not inhibit high dose lipopolysaccharide-induced interleukin-1beta immunoreactivity in rat brain and pituitary gland.

In the present study, we examined whether the vagus nerve is involved in mediating lipopolysaccharide (LPS)-induced appearance of IL-1beta immunoreactive cells in the brain and pituitary gland. Rats were either sham-operated or subjected to subdiaphragmatic vagotomy. Four weeks later, pyrogen free saline or 400 microg/kg LPS was administered to the rats intraperitoneally. Four and 8 h later, the animals were intracardially perfused with 4% paraformaldehyde and tissues were prepared for IL-1beta immunocytochemistry. IL-1beta positive cells were observed at both time-intervals after LPS administration in the choroid plexus, meninges, circumventricular organs and pituitary gland of both sham-operated and vagotomized rats. We conclude that under the conditions studied, the vagus nerve does not mediate LPS-induced appearance of IL-1beta in the rat brain and pituitary gland.

Animals↗

Angiotensin II receptors in paraventricular nucleus, subfornical organ, and pituitary gland of hypophysectomized, adrenalectomized, and vasopressin-deficient rats.

Angiotensin II has been implicated in the regulation of adrenocorticotropin and vasopressin secretion. Angiotensin II may influence the secretion of these hormones either directly at the pituitary gland or by increasing corticotropin-releasing hormone or vasopressin release from cells that are located in the paraventricular hypothalamic nucleus. Pituitary hormone release may also be influenced by circulating angiotensin II through receptors outside the blood-brain barrier in the subfornical organ. We have used alterations in angiotensin II receptors in hypophysectomized, adrenalectomized, and vasopressin-deficient Brattleboro rats as indicators of the activity of angiotensin II in the regulation of adrenocorticotropin and vasopressin secretion. Angiotensin receptor number in the paraventricular nucleus and the subfornical organ, but not in the anterior pituitary gland, was significantly decreased by adrenalectomy, and this effect was reversed by corticoids. Vasopressin deficiency decreased angiotensin receptors in the subfornical organ and increased them in the anterior pituitary gland but did not affect angiotensin II binding in either magnocellular or parvocellular subnucleus of the paraventricular nucleus. Our results suggest that angiotensin II may have a corticoid-dependent role in the regulation of corticotropin-releasing hormone secretion, which could be important in the adaptation to elevated corticosterone secretion in stress.

Adrenalectomy↗

CT of the pituitary gland in multiple endocrine neoplasia type 1 syndrome.

Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disease involving tumors of the parathyroid, pancreas, and pituitary glands. Over 50% of the patients with this syndrome will have involvement of the pituitary gland. Computed tomography (CT) of the head was performed in 21 of 42 patients with the clinical diagnosis of MEN-1. CT demonstrated pituitary abnormalities in 15 patients, 13 of whom had pituitary endocrine dysfunction. The most common endocrinopathy was hyperprolactinemia, documented in nine patients. Hypopituitarism due to nonfunctional adenoma was found in two patients, and acromegaly and Cushing disease in individual cases. The appearance of the pituitary gland in CT evaluation of the sella in patients with MEN-1 is presented.

Adenoma↗

Effect of alterations in thyroid status on the metabolism of thyroxine and triiodothyronine by rat pituitary gland in vitro.

The metabolism of thyroxine (T(4)) was studied in slices of rat pituitary gland and liver from the same animal incubated in vitro with [(125)I]T(4) and 10 mM dithiothreitol. In the pituitary gland, generation of (125)I-labeled 3,5,3'-triiodothyronine (T(3)), as well as overall T(4) degradation, increased significantly at 24 h after thyroidectomy and by 2 wk were approximately five times control values. Conversely, following a single injection of T(3) (1.5 mug/100 g body wt), values for both functions were significantly decreased at 4 h, and reached a nadir of approximately 20% of control values at 12 and 24 h. Net T(3)-neogenesis accounted for approximately 70% of T(4) degradation in control pituitaries from intact rats. This proportion was increased by thyroidectomy and decreased by T(3) replacement. Indirect evidence indicated that thyroidectomy decreased, and T(3) administration increased, non-T(3) generating pathways of T(4) metabolism, probably 5-monodeiodination leading to formation of 3,3'5'-triiodothyronine (rT(3)). As judged from studies by others, the prompt changes in T(4) metabolism that followed thyroidectomy or T(3) administration could not be explained by changes in pituitary cell type. Changes in T(3)-neogenesis in liver were the converse of those in pituitary, and were much slower to occur. In the thyroidectomized rat, administration of cycloheximide resulted in an approximately 60% inhibition of pituitary T(3)-neogenesis and T(4)-degradation at 4 h, a time-course of inhibition similar to that produced by T(3). Unlike T(3), cycloheximide did not alter the proportion of T(4) degradation that could be accounted for by T(3) neogenesis, and appeared, therefore, to inhibit both T(3) generating and non-T(3) generating pathways. The time-course of the inhibitory effect of cycloheximide on the incorporation of [(3)H]leucine into hemipituitaries in vitro was parallel to its effect on T(3)-neogenesis. The inhibition of T(3)-neogenesis that occurred when T(3) and cycloheximide were given together did not exceed the effect of T(3) alone, suggesting a common mechanism of action of the two agents. FROM THE FOREGOING INFORMATION, THE FOLLOWING TENTATIVE CONCLUSIONS ARE DRAWN: (a) turnover of the 5'-monodeiodinase for T(4) in rat pituitary is rapid, substantially more so than in liver; (b) thyroidectomy enhances, and T(3) inhibits, the conversion of T(4) to T(3) in the pituitary; these manipulations have opposite effecs on the non-T(3) generating pathways of T(4) metabolism, probably the 5-monodeiodination of T(4) that produces rT(3); (c) these changes are probably the result of parallel effects on the synthesis of the corresponding enzymes; (d) the changes in T(3)-neogenesis described may permit an intrapituitary feedback mechanism that damps the changes in TSH secretion mediated by classical feedback regulatory control; (e) the effects of hypothyroidism and T(3)-replacement on T(3)-neogenesis and overall T(4) degradation in liver were opposite to those produced in the pituitary. Hence, among differing tissues, the same stimuli may produce greatly different responses in pathways of peripheral T(4) metabolism, thus making possible differing metabolic sequelae within each.

Animals↗

The effects of ad libitum overfeeding and moderate and marked dietary restriction on age-related spontaneous pituitary gland pathology in Sprague-Dawley rats.

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of aged-related pituitary gland changes in Sprague-Dawley (SD) rats. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72-79% of AL (group 2), DR at 68-72% of AL (group 3) or DR at 47-48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights and insulin-like growth factor 1 (IGF-1) serum levels were measured at interim and final necropsies. Serum levels of prolactin (PRL), progesterone, estradiol, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured at 53 and/or 106 weeks. In addition to the routine histopathologic examination, determination of 7 stereologic parameters after pituitary immunohistochemistry of PRL, growth hormone (GH) and BrdU was done in both sexes at 13, 26, and 53 weeks. Body and pituitary weights were proportional to the food intake. In AL-fed rats, hyperplastic and neoplastic changes developed early and progressed with age, affecting almost all animals by 106 weeks. These changes were associated with high PRL serum levels. Pituitary adenomas were the most common cause of death in both sexes. In DR rats, a delayed onset and a decreased incidence of pituitary tumors were observed in association with decreased serum IGF-1, PRL, estradiol, and LH levels. The results of the stereological analysis demonstrated that, compared to AL-fed rats, pituitary glands from DR rats contained lower PRL and GH secreting cell volumes, and a lower epithelial cell BrdU labeling index, which correlated with a lower incidence of pituitary tumors at study termination. Moderate and marked degrees of DR delayed the onset of pituitary tumors in a temporal- and dose-related manner. In contrast to marked DR, which dramatically reduced the incidence of hyperplastic and neoplastic pituitary gland changes, moderate DR delayed the onset but did not prevent the development of pituitary tumors.

Aging↗

Tumor necrosis factor-alpha in macrophages of heart, liver, kidney, and in the pituitary gland.

Tumor necrosis factor-alpha (TNFalpha) is an important mediator in bacterial lipopolysaccharide (LPS)-induced fever and shock. New data on TNFalpha-producing macrophages in heart, pituitary gland, kidneys and liver in correlation with TNFalpha plasma levels are reported here. In adult rabbits, core temperature and TNFalpha plasma levels are significantly increased at 3 and 24 h after treatment with LPS. After a delay of 6-12 h, the number of TNFalpha-containing macrophages, determined by immunohistochemistry, increases more than fivefold in all organs investigated. With the exception of the pituitary gland, the increase in cell number is correlated with the degree of cellular injury, indicating the involvement of TNFalpha in LPS-induced organ damage that is accompanied by the synthesis of the cytokine. Cortisol levels also increase for at least 24 h after LPS treatment, show peak values 6 h after interleukin-1 treatment, and are unchanged after TNFalpha treatment, indicating the different effects of these factors on the hypothalamo-hypophyseal-adrenocortical axis. This study provides evidence that macrophageal TNFalpha of multi-organ origin is involved in LPS-induced tissue injury and supports the concept of a systemic inflammatory response syndrome. We also show for the first time that in the anterior lobe of the pituitary gland TNFalpha is a normal constituent in cells producing growth hormone but not ACTH. Moreover, most cells of the intermediate lobe are positive for TNFalpha.

Animals↗

The vascularization of the pituitary gland of the chicken (Gallus domesticus). A scanning electron microscope study of vascular corrosion casts.

Microvascular corrosion casts of the pituitary gland of one to nine-day-old chickens (Gallus domesticus, white leghorn hybrids) were analysed with the scanning electron microscope. Results show that the chicken median eminence is supplied by branches of the infundibular and the neural-lobe arteries. They form a flat two-dimensional primary capillary plexus, which lacks any capillary loops and is continuous with the plexus in the neural lobe. The capillaries occupy about 60% of the total area of the median eminence. A subependymal plexus is present, showing no contact with the plexus of the median eminence. The chicken neural lobe consists of many hollow buds. These buds are supplied by branches of the neural-lobe artery, which gives rise to a two-dimensional capillary meshwork similar to that of the median eminence. An anterior group of portal vessels, comprising 14-16 vessels with a mean diameter of 37 microns, and a posterior group of portal vessels, comprising 2-4 shorter and slightly thinner vessels, arise from the median eminence are the sole blood supply for the adenohypophysis (distal lobe). Anterior portal vessels supply the cephalic lobe and the most rostral area of the caudal lobe, and posterior portal vessels supply the caudal lobe of the distal lobe. There are no short portal vessels connecting the neural lobe with the distal lobe. The (sinusoidal) capillary bed of the distal lobe is laminated. The chicken hypophysis drains into the cavernous sinus, which empties into the cerebral carotid veins. Within the period studied (days 1-9 after hatching) no age-related changes were found.

Animals↗

Arterial supply of the human anterior pituitary gland.

The vascular anatomy of the anterior lobe (AL) of 182 previously injected human pituitary glands was examined. Three different techniques of injection using India ink and acrylic paints were performed to establish a direct arterial supply to the AL. In 81% of the cases, end-arteries were found in the AL. Their participation in the vascularization of the adenohypophysis is variable from a small subcapsular area to almost the entire lateral parts of the AL. Arteries playing some role in the perfusion of the AL are subdivided into infra- and supradiaphragmatic, according to their topography in relation to the diaphragma sellae. Evidence of the presence of end-arteries in the AL is in disagreement with the generally accepted concept of a purely portal supply to this part of the pituitary gland.

Adolescent↗

Receptor-mediated actions of corticotropin-releasing factor in pituitary gland and nervous system.

High-affinity corticotropin-releasing factor (CRF) receptors which mediate the actions of the hypothalamic peptide on adrenocorticotropic hormone (ACTH) release have been identified in the rat anterior pituitary gland. Occupancy of the pituitary receptor by CRF agonists stimulates ACTH release via activation of adenylate cyclase and cyclic adenosine monophosphate dependent protein kinase. In the regulation of ACTH secretion, the effects of CRF on the corticotroph are integrated with the stimulatory actions of cyclic adenosine monophosphate-independent stimuli such as angiotensin II, vasopressin and norepinephrine, and the inhibitory effects of glucocorticoids and somatostatin. In contrast to the major importance of the inhibitory effect of glucocorticoid feedback on ACTH secretion, somatostatin has relatively little effect on CRF-stimulated ACTH release in the normal rat corticotroph. Following adrenalectomy, the progressive elevation of plasma ACTH levels is accompanied by a concomitant decrease in pituitary CRF receptors. The postadrenalectomy loss of CRF receptors, which is prevented by dexamethasone treatment, is caused by a combination of occupancy and processing of the pituitary sites during increased secretion of the hypothalamic peptide. Recently, specific receptors for CRF have been localized in the rat and monkey brain and adrenal medulla, where they are also coupled to adenylate cyclase. Brain CRF receptors are most abundant in the cerebral and cerebellar cortices and in structures related to the limbic system and control of the autonomic nervous system. The actions of CRF on the central and peripheral nervous systems, as well as on the pituitary gland, emphasize the role of CRF as a key hormone in the integrated response to stress.

Adrenocorticotropic Hormone↗

Immunoreactive calcitonin in the rat anterior pituitary gland and its localization in thyrotrophs.

The distribution of those cells in the anterior pituitary gland of the rat which stain immunohistochemically with rabbit anti-human calcitonin serum has been examined. Immunoreactive cells were confined primarily to the ventral surface of the gland and possessed both a distribution and morphology distinct from the corticotrophs. Staining of serial thin sections with rabbit anti-rat TSH-subunit serum resulted in an immunoreaction in those cells that stained for calcitonin. However, not all the thyrotrophs gave a positive immunoreaction for calcitonin. It is concluded from this study that it is inappropriate to attribute calcitonin as being part of the 31K-dalton precursor for adrenocorticotropin, a hypothesis that was proposed earlier. In the immunohistochemical reaction with anti-calcitonin serum, it was found that relatively high concentrations of antigen (500 micrograms/ml) were required in absorption experiments in order to inhibit staining. Furthermore, the staining of thyrotrophs with the anti-calcitonin serum was inhibited after preadsorption of the primary antiserum with excess rat beta-TSH (1000 micrograms/ml). Because of these immunochemical characteristics, it is questionable whether the calcitonin-like material observed in the rat pituitary gland is chemically identical to that of thyroidal calcitonin.

Animals↗

Secretion of epidermal growth factor-like mitogens by cultured cells from bovine anterior pituitary glands.

We have partially characterized growth factor activity secreted by early cultures of cells derived from bovine calf pituitary glands. Serum-free, chemically defined culture medium conditioned by pituitary cells stimulated DNA synthesis in rat kidney fibroblasts (NRK cells) equivalent to unconditioned medium containing 3 X 10(-10) M epidermal growth factor (EGF). The conditioned medium contained activity which competed with 125I-EGF for binding to EGF-receptors which was also equivalent to competition by 3 X 10(-10) M EGF in a radioreceptor assay. Secondary pituitary cultures produced about 10-fold more competing activity than did primary cultures and the production rate of the EGF-competing activity by the secondary cultures remained stable for over 4 weeks. Bio-Gel P-60 chromatography in 1 M acetic acid of an extract of conditioned medium resolved three peaks of EGF-competing activity. These peaks chromatographed with apparent mol wts of 17,000, 9,000, and 6,000. These peaks of activity were not as a result of EGF-binding proteins in the culture medium. The 6,000 mol wt peak contained activity which competed equally well with EGF for EGF receptor and antimouse EGF antibody binding. The 17,000 and 9,000 mol wt activities competed more effectively for binding to receptors than antibodies. The mitogenic activity in the three peaks correlated with the receptor-competing activity. However, the 17,000 and 9,000 mol wt peaks but not the 6,000 mol wt peak contained transforming growth factor activity capable of stimulating NRK cells to assume anchorage independent growth. These results suggest that a subpopulation of cells in pituitary glands secrete EGF and EGF-like transforming growth factors.

Animals↗