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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some amphibian brain-melanotrope cell systems are used to study how neuronal and (neuro)endocrine mechanisms convert environmental signals into physiological responses. Pituitary melanotropes release alpha-melanophore-stimulating hormone (alpha-MSH), which controls skin color in response to background light stimuli. Xenopus laevis suprachiasmatic neurons receive optic input and inhibit melanotrope activity by releasing neuropeptide Y (NPY), dopamine (DA) and gamma-aminobutyric acid (GABA) when animals are placed on a light background. Under this condition, they strengthen their synaptic contacts with the melanotropes and enhance their secretory machinery by upregulating exocytosis-related proteins (e.g. SNAP-25). The inhibitory transmitters converge on the adenylyl cyclase system, regulating Ca(2+) channel activity. Other messengers like thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH, from the magnocellular nucleus), noradrenalin (from the locus coeruleus), serotonin (from the raphe nucleus) and acetylcholine (from the melanotropes themselves) stimulate melanotrope activity. Ca(2+) enters the cell and the resulting Ca(2+) oscillations trigger alpha-MSH secretion. These intracellular Ca(2+) dynamics can be described by a mathematical model. The oscillations travel as a wave through the cytoplasm and enter the nucleus where they may induce the expression of genes involved in biosynthesis and processing (7B2, PC2) of pro-opiomelanocortin (POMC) and release (SNAP-25, munc18) of its end-products. We propose that various environmental factors (e.g. light and temperature) act via distinct brain centers in order to release various neuronal messengers that act on the melanotrope to control distinct subcellular events (e.g. hormone biosynthesis, processing and release) by specifically shaping the pattern of melanotrope Ca(2+) oscillations.
Comp Biochem Physiol B Biochem Mol Biol 2002 May
PMID:Multiple control and dynamic response of the Xenopus melanotrope cell. 1199 27

Immunohistochemistry is part of the routine diagnosis of the neuroendocrine tumors. In our study, we included 52 paragangliomas with various localizations by routine histology and immunohistochemistry. In order to increase the diagnostic specificity, a complex immunohistochemistry panel has been performed consisting of Bcl-2, Ki-67, Bax and Pituitary Adenylate Cyclase-Activating Peptide (PACAP), somatostatin, VIP and Calcitonin Gene Related Peptide (CGRP). After heat induced antigen retrieval, the immunostaining was performed by StreptABC using DAB as a chromogen. We were the first to demonstrate the presence of Bax and PACAP in paragangliomas. Some of the used markers are of prognostic value. The relationship between Bcl-2 and Bax is decisive in generating the final response to the input apoptotic signals. The Ki-67 antigen staining has gained wide acceptance in prognostic evaluation of other tumor types. We noted a small number of Ki-67 positive cases, which signifies a low mitotic activity of these tumors and a relatively high number of Bax positivities (32.9%) and the much lower number of Bcl-2 positivities (11.39%), and could explain the benign behaviour of paragangliomas.
J Cell Mol Med
PMID:Immunohistochemical features of paragangliomas. 1206 90

The suprachiasmatic nucleus (SCN) generates circadian rhythms which are synchronised to the environmental light/dark cycle via the retinohypothalamic tract (RHT). Pituitary adenylate cyclase activating polypeptide (PACAP) and glutamate, two transmitters co-stored in the rat retinohypothalamic tract, are involved in photic entrainment of the circadian pacemaker, but their functional interplay is poorly understood. Homer proteins are involved in glutamatergic receptor function and signalling. By quantitative in situ hybridisation histochemistry we found that light stimulation of rats at early and late night induced Homer-1 gene expression in the SCN at time points where light induces phase-delay or phase-advance, respectively. Using a rat brain slice model Homer-1 mRNA levels in the SCN displayed a modest diurnal variation similar to that in vivo. The changes in Homer-1 gene expression after in vitro stimulation with PACAP and/or glutamate differed at early and late night. Nanomolar PACAP induced Homer-1 gene expression at both early and late night while glutamate was only able to increase Homer-1 mRNA level at early night. PACAP in micromolar concentration had no effect per se, but inhibited the glutamate induced Homer-1 response at early night, while at late night co-administration of PACAP and glutamate mediated a slight induction of Homer-1 gene expression. In conclusion, the RHT transmitters PACAP and glutamate could be responsible for the light-induced expression of Homer-1 in the SCN, and Homer-1 seems to be differentially regulated by the two transmitters at early and late night.
Brain Res Mol Brain Res 2002 Sep 30
PMID:Homer-1 mRNA in the rat suprachiasmatic nucleus is regulated differentially by the retinohypothalamic tract transmitters pituitary adenylate cyclase activating polypeptide and glutamate at time points where light phase-shifts the endogenous rhythm. 1239 10

Pituitary adenylate cyclase activating polypeptide (PACAP) was first isolated from ovine hypothalamus and is known to act as a tropic factor in various cells. Recent report revealed the expression of PACAP and the PACAP type I (PAC(1)) receptor in human and rat placentas at term. Placenta is a critical organ that synthesizes several growth and angiogenic factors for its own growth as well as fetal development. However, there is little information regarding the expression pattern and cellular localization of PACAP and PAC(1) during pregnancy. The aim of this study was to define the expression and distribution of PACAP and PAC(1) receptor mRNAs in the rat placenta during pregnancy. PACAP and PAC(1) receptor mRNAs were expressed in decidual cells, chorionic vessels, and stromal cells of the chorionic villi. Interestingly, the expression of these genes varied with the day of gestation. For example, PACAP and PAC(1) receptor mRNAs expressed in decidual cells on day 13.5 and 15.5, their expression was strong in chorionic vessels and stromal cells of the chorionic villi within the labyrinth zone on day 17.5, 19.5, and 21.5. In fact, as gestation advanced, the expression of PACAP and PAC(1) receptor mRNAs in the decidua cells disappeared, as their high expression became evident in the chorionic vessels and stromal cells of the chorionic villi. Our finding that PACAP and the PAC(1) receptor are co-localized and their genes seemingly co-regulated within specific placental areas, strongly suggest that this peptide may play an important role, as an autoregulator or pararegulator via its PAC(1) receptor, in physiological functioning of the placenta for gestational maintenance.
Mol Reprod Dev 2003 Jan
PMID:Expression patterns of pituitary adenylate cyclase activating polypeptide and its type I receptor mRNAs in the rat placenta. 1242 Feb 96

Cushing's disease or pituitary-dependent hyperadrenocorticism (PDH) is common in dogs and rare in cats. PDH is caused by a pituitary tumor producing adrenocorticotropin (ACTH). Pituitary imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is required to assess the size and location of the pituitary adenoma in relation to the surgical landmarks. In a specialized veterinary institution, microsurgical transsphenoidal hypophysectomy has proven to be a safe and effective treatment for dogs (n=84) and cats (n=7) with Cushing's disease. Pituitary surgery requires a team approach and the neurosurgeon performing hypophysectomies must master a learning curve. The surgical results compared favorably with those for dogs with PDH treated medically with mitotane at the same institution. The recurrence rate after initially successful surgery increases with longer follow up-times. Pituitary function testing in 39 dogs with PDH treated with hypophysectomy revealed that, much more so than the other adenohypophyseal cell types, residual corticotropes present in the sella turcica after surgery are functional. Such normal ACTH secreting cells may maintain normocorticism whereas residual adenoma cells may lead to mild recurrence after relatively long periods of remission. Microsurgical transsphenoidal hypophysectomy is an effective treatment for canine and feline Cushing's disease.
Mol Cell Endocrinol 2002 Nov 29
PMID:Progress in transsphenoidal hypophysectomy for treatment of pituitary-dependent hyperadrenocorticism in dogs and cats. 1243 1

During bovine embryogenesis, bovine growth hormone (bGH) contributes to proliferation, differentiation, and modulation of embryo metabolism. Pituitary-specific transcription factor-1 (Pit-1) is a transcription factor that binds to promoters of GH, prolactin (PRL), and thyroid-stimulating hormone-beta (TSHbeta) encoding genes. A polymorphism in the fifth exon of the bGH gene resulting in a leucine (Leu) to valine (Val) substitution provides an Alu I restriction site when the Leu allele is present. To determine the onset of embryonic expression of the bGH gene, oocytes derived from ovaries homozygous for Leu alleles were fertilized in vitro with spermatozoa obtained from a Val homozygote. For each developmental stage examined, three separate pools of embryos composed of approximately 100 cell samples underwent RNA isolation, reverse transcription to cDNA, and amplification by nested PCR (nPCR). Bovine GH gene transcripts were identified at 2- to 4-cell (n = 162), 8- to 16-cell (n = 73), morulae (n = 51), and blastocyst (n = 15) stages. Likewise, transcripts for Pit-1 were detected at 2-cell (n = 125), 4-cell (n = 114), 8-cell (n = 56), 12-to-32-cell (n = 32), morulae (n = 68), and blastocyst (n = 14) stages. After digestion with Alu1, bGH cDNA was genotyped by restriction fragment length polymorphism (RFLP) analysis. Bovine GH mRNA was present in all pools of stages examined. Both Leu and Val alleles (maternal and paternal) were only detected in pools of embryos that had reached 8- to 16-cell stage. Results suggest that transcription of the bGH gene begins at the 8- to 16-cell stage in bovine embryos, possibly under control of the transcription factor, Pit-1, and that RFLP analysis of the bGH gene can be used to determine parental origin of transcripts in early embryonic development.
Mol Reprod Dev 2003 Mar
PMID:Expression of growth hormone and its transcription factor, Pit-1, in early bovine development. 1254 60

To determine the role of each estrogen receptor (ER) form (ERalpha, ERbeta) in mediating the estrogen actions necessary to maintain proper function of the hypothalamic-pituitary-gonadal axis, we have characterized the hypothalamic-pituitary-gonadal axis in female ER knockout (ERKO) mice. Evaluation of pituitary function included gene expression assays for Gnrhr, Cga, Lhb, Fshb, and Prl. Evaluation of ovarian steroidogenic capacity included gene expression assays for the components necessary for estradiol synthesis: i.e. Star, Cyp11a, Cyp17, Cyp19, Hsd3b1, and Hsd17b1. These data were corroborated by assessing plasma levels of the respective peptide and steroid hormones. alphaERKO and alphabetaERKO females exhibited increased pituitary Cga and Lhb expression and increased plasma LH levels, whereas both were normal in betaERKO. Pituitary Fshb expression and plasma FSH were normal in all three ERKOs. In the ovary, all three ERKOs exhibited normal expression of Star, Cyp11a, and Hsd3b1. In contrast, Cyp17 and Cyp19 expression were elevated in alphaERKO but normal in betaERKO and alphabetaERKO. Plasma steroid levels in each ERKO mirrored the steroidogenic enzyme expression, with only the alphaERKO exhibiting elevated androstenedione and estradiol. Elevated plasma testosterone in alphaERKO and alphabetaERKO females was attributable to aberrant expression of Hsd17b3 in the ovary, representing a form of endocrine sex reversal, as this enzyme is unique to the testes. Enhanced steroidogenic capacity in alphaERKO ovaries was erased by treatment with a GnRH antagonist, indicating these phenotypes to be the indirect result of excess LH stimulation that follows the loss of ERalpha in the hypothalamic-pituitary axis. Overall, these findings indicate that ERalpha, but not ERbeta, is indispensable to the negative-feedback effects of estradiol that maintain proper LH secretion from the pituitary. The subsequent hypergonadism is illustrated as increased Cyp17, Cyp19, Hsd17b1, and ectopic Hsd17b3 expression in the ovary.
Mol Endocrinol 2003 Jun
PMID:Characterization of the hypothalamic-pituitary-gonadal axis in estrogen receptor (ER) Null mice reveals hypergonadism and endocrine sex reversal in females lacking ERalpha but not ERbeta. 1262 16

Human prolactin is a 199-residue (23 kDa) protein closely related to growth hormone and placental lactogen with properties and functions resembling both a hormone and a cytokine. As a traditional hormone, prolactin is produced by lactotrophic cells in the pituitary and secreted into the bloodstream where it acts distally to regulate reproduction and promote lactation. Pituitary cells store prolactin in secretory granules organized around large prolactin aggregates, which are produced within the trans layer of the Golgi complex. Extrapituitary prolactin is synthesized by a wide variety of cells but is not stored in secretory granules. Extrapituitary prolactin displays immunomodulatory activities and acts as a growth factor for cancers of the breast, prostate and tissues of the female reproductive system. We have determined the tertiary structure of human prolactin using three-dimensional (3D) and four-dimensional (4D) heteronuclear NMR spectroscopy. As expected, prolactin adopts an "up-up-down-down" four-helical bundle topology and resembles other members of the family of hematopoietic cytokines. Prolactin displays three discrete structural differences from growth hormone: (1) a structured N-terminal loop in contact with the first helix, (2) a missing mini-helix in the loop between the first and second helices, and (3) a shorter loop between the second and third helices lacking the perpendicular mini-helix observed in growth hormone. Residues necessary for functional binding to the prolactin receptor are clustered on the prolactin surface in a position similar to growth hormone. The backbone dynamics of prolactin were investigated by analysis of 15N NMR relaxation phenomena and demonstrated a rigid four-helical bundle with relatively mobile interconnecting loops. Comparison of global macromolecular tumbling at 0.1mM and 1.0mM prolactin revealed reversible oligomerization, which was correlated to dynamic light scattering experiments. The existence of a reversible oligomerization reaction in solution provides insight into previous results describing the in vitro and in vivo aggregation properties of human prolactin.
J Mol Biol 2003 May 16
PMID:The tertiary structure and backbone dynamics of human prolactin. 1272 45

Hormone-producing cells in the rat anterior pituitary gland are not randomly distributed; rather, there are specific topographic affinities among five cell types (Noda et al., Acta Histochem. Cytochem. 2001;34:313-319). In this study we reconstructed these affinities, at least partially, in primary monolayer culture. Pituitary cells collected from adult male rats were enzymatically dispersed and cultured for 72 hr at a density of 1 x 10(5) cells/cm(2). We double-immunostained cells using antibodies against hormones, and then used confocal laser microscopy to examine the ability of the cells to attach to each other. We also statistically analyzed the affinity of all combinations of the five types of hormone-producing cells. We observed clusters by electron microscopy to identify junctional complexes between the cells. Confocal laser microscopy indicated that the features and attachment patterns of hormone-producing cells in vivo were similar to those in vitro. Statistical analyses revealed that the rates at which the five types of hormone-producing cells attached to growth hormone (GH)-, prolactin (PRL), and luteinizing hormone (LH)-producing cells were unequal, which suggests there are specific topographic affinities. The specific rates of adrenocorticotropic hormone (ACTH)-producing cell attachment to GH cells, LH to PRL cells, and PRL to LH cells were high, whereas that of PRL attachment to PRL cells was low. In addition, the rates correlated with the data from our previous in vivo study. Ultrastructural observations revealed few junctional complexes between hormone-producing cells. These results indicate that anterior pituitary hormone-producing cells can attach to specific types of cells by means of specific and/or nonspecific adhesion factors, and can reconstruct the topographic nature of the pituitary gland.
Anat Rec A Discov Mol Cell Evol Biol 2003 Jun
PMID:Rat anterior pituitary cells in vitro can partly reconstruct in vivo topographic affinities. 1274 Sep 49

Estrogen plays an important role in the regulation of gonadotropin production in vertebrates. In this study, we isolated the estrogen receptor (ER) alpha cDNA from the goldfish pituitary. Primers for ERalpha were designed based on the similarity of selected regions (C and E domains) of known ER genes. Full-length cDNA sequence for ERalpha was determined by 3' and 5' RACE procedures. ERalpha cDNA clone was found to contain 2087 nucleotides including an open reading frame that encodes 564 amino acids, with a molecular weight of 62.8 kDa. We also cloned ERbeta-1 and ERbeta-2 from the published information and investigated the expression pattern of these ER subtypes in a variety of tissues in male and female goldfish by reverse transcriptase-polymerase chain reaction (RT-PCR). Significant variations in the relative expression of ERalpha, ERbeta-1 and ERbeta-2 were observed in different tissues in male and female goldfish. Pituitary was found to have the highest expression level of ERalpha in both male and female goldfish. Significantly, lower levels of ERalpha expression were observed in the brain, ovary, testis, liver, muscle, heart and intestine. Ovary and testis were found to have higher transcript levels of ERbeta-1 with much lower levels in the brain, pituitary, liver, muscle and heart. The ERbeta-2 was found to be expressed strongly in the pituitary followed by intestine with lower expression in other tissues. The present study provides molecular characterization of ERalpha, and information on tissue specific distribution of different ER subtypes in male and female goldfish.
Mol Cell Endocrinol 2003 Jun 30
PMID:Molecular cloning of estrogen receptor alpha and expression pattern of estrogen receptor subtypes in male and female goldfish. 1285 Feb 91


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