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PubMed2001

Immunohistochemical analysis of p27 (Kip1) in human pituitary glands and in various types of pituitary adenomas.

p27 (Kip1) plays regulatory roles in the cell cycle by inhibiting the activity of cyclin dependent kinases (CDKs). This immunohistochemical study is aimed at elucidating the expression of p27 in human pituitary and in various types of pituitary adenomas in order to clarify its role in the regulation of proliferation. Sixteen normal pituitary glands and 179 human pituitary adenomas were used for immunohistochemical studies. The tissues were fixed in 10% formalin and embedded in paraffin. Indirect peroxidase method was performed after heat-induced antigen retrieval using a monoclonal antibody against p27 protein. p27 protein was expressed in the nuclei of all 16 normal human pituitary glands. p27 protein was also expressed in 128 of 179 cases of pituitary adenomas (71.5%). A marked decrease of p27 expression was noted in ACTH-secreting adenomas, 8/20 (40.0%), compared with other types of pituitary adenomas--GH-secreting adenomas, 35/46 (76.1%); PRL-secreting adenomas, 22/33 (66.7%); TSH-secreting adenomas, 8/11 (72.7%); and nonfunctioning adenomas, 55/69 (79.7%). These results suggest that p27 may play some role in the regulation of proliferation in all types of pituitary adenomas. The lower levels of p27 in ACTH-secreting adenoma is of particular interest with respect to the intermediate lobe-derived pituitary tumor developed in p27 knockout mice.

Adenoma↗
PubMed2005

Thyroid and pituitary gland development from hatching through metamorphosis of a teleost flatfish, the Atlantic halibut.

Fish larval development, not least the spectacular process of flatfish metamorphosis, appears to be under complex endocrine control, many aspects of which are still not fully elucidated. In order to obtain data on the functional development of two major endocrine glands, the pituitary and the thyroid, during flatfish metamorphosis, histology, immunohistochemistry and in situ hybridization techniques were applied on larvae of the Atlantic halibut (Hippoglossus hippoglossus), a large, marine flatfish species, from hatching through metamorphosis. The material was obtained from a commercial hatchery. Larval age is defined as day-degrees (D degrees =accumulated daily temperature from hatching). Sporadic thyroid follicles are first detected in larvae at 142 D degrees (27 days post-hatch), prior to the completion of yolk sack absorption. Both the number and activity of the follicles increase markedly after yolk sack absorption and continue to do so during subsequent development. The larval triiodothyronine (T(3)) and thyroxine (T(4)) content increases, subsequent to yolk absorption, and coincides with the proliferation of thyroid follicles. A second increase of both T(3) and T(4) occurs around the start of metamorphosis and the T(3) content further increases at the metamorphic climax. Overall, the T(3) content is lower than T(4). The pituitary gland can first be distinguished as a separate organ at the yolk sack stage. During subsequent development, the gland becomes more elongated and differentiates into neurohypophysis (NH), pars distalis (PD) and pars intermedia (PI). The first sporadic endocrine pituitary cells are observed at the yolk sack stage, somatotrophs (growth hormone producing cells) and somatolactotrophs (somatolactin producing cells) are first observed at 121 D degrees (23 days post-hatch), and lactotrophs (prolactin producing cells) at 134 D degrees (25 days post-hatch). Scarce thyrotrophs are evident after detection of the first thyroid follicles (142 D degrees ), but coincident with a phase in which follicle number and activity increase (260 D degrees ). The somatotrophs are clustered in the medium ventral region of the PD, lactotrophs in the anterior part of the PD and somatolactotrophs are scattered in the mid and posterior region of the pituitary. At around 600 D degrees , coinciding with the start of metamorphosis, somatolactotrophs are restricted to the interdigitating tissue of the NH. During larval development, the pituitary endocrine cells become more numerous. The present data on thyroid development support the notion that thyroid hormones may play a significant role in Atlantic halibut metamorphosis. The time of appearance and the subsequent proliferation of pituitary somatotrophs, lactotrophs, somatolactotrophs and thyrotrophs indicate at which stages of larval development and metamorphosis these endocrine cells may start to play active regulatory roles.

Animals↗
PubMed1992

The pituitary gland in hyperthyroidism.

The pituitary glands of 33 patients (24 women and 9 men, 18 to 78 years old) who died in thyrotoxicosis (18 with Graves' disease and 15 with toxic multinodular goiter [Plummer's disease]) were examined by histologic and immunocytologic methods. Thirteen patients (39%) died in "thyroid storm." The avidin-biotin-peroxidase complex immunostaining method was used to demonstrate the spectrum of pituitary hormones, including growth hormone, prolactin, adrenocorticotropic hormone, thyrotropin, follicle-stimulating hormone, luteinizing hormone, and alpha-subunit. The most striking finding was a pronounced decrease or loss of immunoreactivity to thyrotropin in all thyrotoxic cases, a consistent change that allowed ready distinction of thyrotoxic from euthyroid pituitary glands. When immunoreactive thyrotrophs were identified, they were sparse and small and demonstrated only faint thyrotropin reactivity. No morphologic differences were noted between the pituitary glands of patients with Graves' disease or Plummer's disease or between sexes. Loss of thyrotropin immunoreactivity was found to be reversible in that thyrotropic cells in the pituitary glands of 16 additional concurrently studied patients, who had thyrotoxicosis but were treated and subsequently had normal thyroid function or hypothyroidism, appeared normal or even hyperplastic. Other types of adenohypophysial cells in both the thyrotoxic and the successfully treated groups exhibited no abnormalities. Pituitary adenomas were incidental findings in 6 of the 33 patients (18%). Their immunotypic spectrum included three prolactin-immunoreactive tumors, two growth hormone-containing adenomas (one of which was plurihormonal), and one tumor with follicle-stimulating hormone and luteinizing hormone; no thyrotropin-containing adenomas were noted. No examples of pituitary hyperplasia were encountered in pituitary glands of thyrotoxic patients, and no hypophysitis or fibrosis was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1984

Oxytocin content of human fetal pituitary glands.

Seventeen human fetal and neonatal pituitary glands were removed at necropsy, and analyzed for oxytocin content by a specific and sensitive radioimmunoassay, after homogenization in 0.4M acetic acid. Serial dilution of the pituitary extract showed parallelism with the oxytocin standard curve on the radioimmunoassay. Column chromatography of the pituitary gland extract gave a single peak of immunoreactive oxytocin as determined by the radioimmunoassay. In eight fetuses, 14 to 17 weeks' gestation, pituitary gland oxytocin was 10.2 +/- 5.9 ng/gland (mean +/- SE), whereas an 18-week fetus had 5.8 ng of oxytocin per gland. Pituitary gland oxytocin content increased to 38.4 ng/gland in a 20-week fetus removed at hysterectomy, and 31.6 ng/gland in a 26-week fetus. Fetal pituitary gland oxytocin values were 22.1 ng/gland and 57.0 ng/gland at 32 weeks and increased significantly to 544.3 +/- 33.8 ng/gland in 1- to 5-day-old term newborn infants (n = 3). However, a 13-day-old term newborn infant had 3.7 ng of oxytocin per pituitary gland. The increased pituitary gland oxytocin content with advancing gestation was due to a significant increase in oxytocin concentration rather than to an increase in the weight of the pituitary gland. The findings indicate that oxytocin is present in fetal pituitary glands as early as 14 to 17 weeks' gestation and increases at term to 50 and 13 to 14 times more than in early midtrimester and early third-trimester pregnancy, respectively.

Chromatography, Gel↗
PubMed1984

Stimulation of 17 beta-hydroxy steroid dehydrogenase in the rat anterior pituitary gland by progesterone.

Anterior pituitary gland and hypothalamic 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity was measured in the immature castrated estradiol primed rat to determine if differences in enzyme activity could explain the progesterone induced reduction of bound estradiol nuclear receptors of the anterior pituitary gland but not the hypothalamus. Higher levels of 17 beta-HSD activity were found in the anterior pituitary gland as compared to the hypothalamus. The enzyme activity in the anterior pituitary gland was stimulated by progesterone administered either in combination with estradiol for 4 days or as a single injection following 4 days of estradiol priming. No progesterone effects were found on hypothalamic 17 beta-HSD. Under the experimental conditions used, progesterone administration did not alter uterine 17 beta-HSD. An increase in anterior pituitary gland and uterine 17 beta-HSD was also induced by estrogen administration.

17-Hydroxysteroid Dehydrogenases↗
PubMed1976

Glycoproteins in membranes of secretory granules of the anterior pituitary gland.

Rat anterior pituitary glands were examined by electron microscopy after staining with five different histochemical stains. Histochemical reactions were observed in the cell coat, cell membrane and the membrane surrounding the secretory granules in all anterior pituitary cells following staining with phosphotungstic acid (PTA), chromic acid and PTA, the periodic acid-thiosemicarbazide-silver protein method (PA-TSC-SP) of Thiéry, ruthenium red and concanavalin A. The staining was abolished when the sections were preincubated with pronase, neuraminidase or trypsin and subsequently exposed to PTA, chromic acid and PTA or PA-TSC-SP. The possible functional role of the glycoproteins present in the membrane surrounding the secretory granules is considered.

Animals↗
PubMed1996

An alternative pathway for clearance of dead lactotropes from rat pituitary gland.

In the pituitary glands of lactating rats there is a striking proliferation of lactotropes during pregnancy and lactation. After the cessation of lactation, the population of lactotropes experiences an extensive programmed cell death of redundant cells until it reaches prepregnancy levels. The regressive changes occurring in lactotropes are autolytic in nature and usually these cells are engulfed by stellate cells. Other involuting lactotropes are mobilized toward the blood capillaries and some go into the capillary lumen for final disposal, presumably in the mononuclear phagocyte system. In this study we report a sequence of events occurring in regressing lactotropes, investigated by a systematic electron microscope analysis of the rat pituitary gland at different periods after interruption of lactation. Direct disposal of degenerating lactotropes and their cell remnants appears to be an alternative pathway for the clearance of the regressing cells that occur extensively among surplus lactotropes following ablactation.

Animals↗
PubMed1975

Characterization of the mannosyl and fucosyl transferases in the ovine anterior pituitary glands.

Ovine anterior pituitary glands contain mannosyl- and fucosyl-transferases localized in the microsomes and able to incorporate mannose or fucose as such from GDP-mannose or GDP-fucose into endogenous glycoproteins. The requirements and conditions necessary for maximum activity were investigated. The value of the Km is very similar for the two enzyme systems, 3 X 10(-7) M in the case of mannosyl-transferases and 5 X 10(-7) M in the case of fucosyl-transferases.

Animals↗
PubMed1977

Effect of estradiol-17 beta on preprolactin messenger ribonucleic acid activity in the rat pituitary gland.

Rat pituitary RNA was translated in the wheat germ system. Preprolactin messenger RNA activity was estimated by adsorption of cell-free products to solid phase antiprolactin. When male rats were injected for 4 days with estradiol-17beta, pituitary preprolactin mRNA activity was increased 2.5- to 3.0-fold over controls. This increase was evident when either total RNA, poly(adenylic acid) RNA, or polysomal RNA was translated in the cell-free system. In male rats receiving daily injections of estradiol-17beta, preprolactin mRNA activity was increased to an apparent maximum of 300% of controls after 7 days of treatment. Our data also indicate that estradiol increases preprolactin mRNA activity per microgram of RNA as well as the pituitary content of RNA. After estradiol treatment was discontinued, preprolactin mRNA activity declined to 50% of the maximum stimulation after approximately 2 days. In ovariectomized retired breeder female rats, a 5-fold increase in preprolactin activity over ovariectomized controls was obtained. In other studies, a 2-fold increase in preprolactin mRNA activity was obtained in male rats 24 h after a single injection of pimozide, a dopamine blocking drug.

Animals↗
PubMed1992

Blood flow in portal systems with special reference to the rat pituitary gland.

Regional pituitary blood flow has been studied in adult female Fischer 344 rats by [14C]iodoantipyrine autoradiography. A general mathematical solution has been derived to allow the calculation of blood flow in the second compartment of a portal system and the proportion of blood "shunted" through the first compartment without exposure to tissue uptake from a knowledge of (a) the volume ratios of the two compartments, (b) the tissue tracer uptakes of the two compartments, and (c) the arterial tracer concentration with respect to time of a freely diffusible tracer. Significant diffusion limitation and/or arteriovenous shunting has been demonstrated in the neurohypophysis, suggesting that the majority of incoming blood is "shunted" unchanged to the adenohypophysis. The mean value of the shunt is 89% (range of 84-93%) for the median eminence and lies between 72% (range of 52-82%) and 73% (range of 59-81%) for the posterior pituitary. Neurohypophysial flow rates of 1.20 (range of 0.99-1.55) ml g-1 min-1 for the median eminence and 1.68 (range of 0.83-3.53) ml g-1 min-1 for the posterior pituitary were measured. These values represent "tissue-available" (nonshunted) flow; estimated mean total (shunted plus nonshunted) neurohypophysial flow rates were 11.7 (range of 9.5-17.5) ml g-1 min-1 for the median eminence and 6.1 (range of 3.1-8.9) ml g-1 min-1 (minimum) for the posterior pituitary. Adenohypophysial blood flow is heterogeneous. In the long portal territory, the flow rate was 1.18 (range of 0.95-1.75) ml g-1 min-1 but short portal territory flow calculation is complicated by an unquantifiable nonportal venous drainage; using the natural limits of zero and 100% gives a minimum adenohypophysial flow rate of 1.42 (range of 0.76-2.07) ml g-1 min-1 and a maximum value of 1.97 (range of 1.03-2.82) ml g-1 min-1.

Algorithms↗
PubMed1984

Regulation of phosphatidylcholine biosynthesis by the methylation pathway in rat pituitary gland.

Rat pituitary extracts catalyze methylation of phosphatidylethanolamine to phosphatidylcholine using S-adenosyl-L-methionine as the methyl donor. In vitro incubation of hemipituitaries with 1 mM 2-methylaminoethanol led to a dose dependent decrease in phosphatidylethanolamine methyltransferase activity as well as the incorporation of the radioactivity from [3H-methyl]-L-methionine into phosphatidyl-choline. The inhibitory effect of 2-methylaminoethanol was selective for phospholipids methylation since protein carboxymethyltransferase and catechol-o-methyltransferase activities were not affected.

Animals↗
PubMed1994

Enhancer-mediated high level expression of mouse pituitary glycoprotein hormone alpha-subunit transgene in thyrotropes, gonadotropes, and developing pituitary gland.

The pituitary hormones LH, FSH, and TSH are heterodimers composed of a common alpha-subunit and unique beta-subunits. We demonstrate that 4.6, 2.7, 1.49 or 0.48 kilobases (kb) mouse alpha-subunit 5'-flanking sequences are sufficient for transgene expression in both gonadotropes and thyrotropes but not in inappropriate pituitary cells. In contrast, transgenes with bovine or human alpha-subunit flanking sequences have been shown to confer reporter gene expression only to gonadotrope cells, suggesting that the elements regulating cell-specific expression may differ between species. Equal levels of reporter gene expression were conferred by 5.0 and 0.48 kb in transiently transfected thyrotrope tumor-derived cells. In contrast, in transgenic mice, high level expression was only obtained with 4.6 kb 5'-flanking sequences, indicating the presence of an enhancer element between 4.6 and 2.7 kb. The 4.6 kb of 5'-flanking sequences are sufficient for both hormonal and developmental regulation of transgene expression. Mice rendered hypothyroid by radiothyroidectomy had significantly higher levels of transgene expression than either hyperthyroid or euthyroid animals. The temporal and spatial pattern of transgene expression in Rathke's pouch paralleled that of the endogenous gene; the onset of transgene expression occurred by embryonic day 9.5. Low level expression of both the transgene and the endogenous alpha-subunit gene were detected in some unexpected peripheral sites, such as the embryonic extraocular and olfactory regions, suggesting that alpha-subunit may have a more diverse role in development than previously considered.

Animals↗
PubMed1982

[Thin-section CT scan of the pituitary gland (author's transl)].

Topographic anatomy of the pituitary fossa was studied by 2 mm thin-section CT scan (Somatom II). Nineteen with normal pituitary (control group) and 20 with suspected pituitary abnormality were selected. Plain and contrast CT were performed in all cases. Contrast CT was carried out immediately after the rapid infusion of 220 ml of 30% iodinated contrast medium. In all of control group but two, pituitary gland was detected as homogenous density and its density was as same as density of normal brain tissues, and was enhanced in degree of about 25 CT number. In 2 cases, small low density was visualized in the pituitary gland. Pituitary gland was differentiated from cavernous sinus was usually higher than the pituitary gland. In abnormal group, the microadenoma of the pituitary gland was diagnosed in 5 cases and 3 out of 5 cases was proved by surgery. All 3 microadenomas proved slightly dense by plain CT and enhanced higher than normal pituitary gland by contrast CT. Polytomograms showed no abnormality of the sella turcica in one of these 3 cases. Although 3 microadenomas were detected by the abnormal enhancement, we are not sure whether all of microadenoma can be detected by CT alone. Arachnoid herniation into the pituitary fossa was diagnosed in 7 of control group and 2 of abnormal group. Four out of these 9 cases were verified by using Metrizamide CT. By plain thin-section CT, the diagnosis of arachnoid herniation seems to be possible without Metrizamide CT.

Adenoma↗