Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In lactating rats, suckling renders mammotropes more responsive to prolactin (PRL)-releasing stimuli and less responsive to PRL-inhibiting secretagogues. We have previously shown that a decrease in the activity of protein phosphatase 2A (PP2A) may be responsible for the decrease in responsiveness to the inhibitory secretagogue dopamine (DA). In our present experiments, we have studied the involvement of the adenylate cyclase (AC), stimulatory and inhibitory GTP-binding proteins and also the role of PP2A in the sensitization phenomenon. Pituitary cells obtained from mother rats separated from their pups for 4 h prior to dispersion (non-suckled), suckled for 10 or 30 min after the separation period (suckled) and without separation (continual suckling) were incubated in the presence of different doses of forskolin to activate AC and DA. In a further study, pituitary cells of non-suckled rats were pretreated with cholera toxin (CTX) or pertussis toxin (PTX) and tested for the stimulatory action of forskolin or TRH on PRL release. Ocadaic acid (OA) pretreatment has been used to investigate the involvement of PP2A. Hormone secretion was measured by the reverse hemolytic plaque assay (RHPA). Our results have shown that cells from non-suckled rats were unresponsive to forskolin. A 10-min suckling stimulus sensitizes pituitary mammotropes to respond with a PRL release to a dose-dependent activation of AC by forskolin. This sensitization of AC becomes a permanent feature of the cells when suckling continues for an additional 20 min. We have also found that pituitary mammotropes from non-suckled dams respond to forskolin or TRH with PRL release when they were preincubated with either PTX or the PP2A inhibitor OA. It clearly indicates that the non-responsive pituitary can be shifted to the responsive stage by uncoupling of inhibitory G-protein from its receptor as well as by inhibition of PP2A. This latter finding, consonant with our previous results, suggests that suckling may cause selective changes in the function of G(i) of mammotropes due to a rapid phosphorylation which can remove tonic, GTP-dependent inhibitory function.
Mol Cell Endocrinol 1999 Mar 25
PMID:Inhibition of protein phosphatase 2A (PP2A) mimics suckling-induced sensitization of mammotropes: involvement of a pertussis toxin (PTX) sensitive G-protein and the adenylate cyclase (AC). 1037 12

Growth hormone (GH) gene expression has been examined in control and transgenic coho salmon containing a transgene comprised of the sockeye salmon GH1 gene under the control of the MT-B promoter from the same species. This transgene dramatically enhances the growth of salmonids, and raises serum GH levels some forty-fold. Transcript levels from this transgene were detected by RT-PCR using construct-specific GH primers in all tissues examined (liver, kidney, skin, intestine, stomach, muscle, spleen, pyloric caeca), and ranged from 0.1 - 9.4 pg/50 microg total RNA in different tissues as estimated by dot blot analysis. Interestingly, GH gene expression was also observed in intestine of control coho salmon by RT-PCR capable of detecting host and transgene transcripts using general primers. Sequence analysis of the intestinal GH mRNA from controls indicated it was derived from the coho GH2 gene. GH mRNA abundance analyzed by northern analysis indicates lower levels are found in large (400-500 g) than small transgenic salmon (20-21 g). No molecular evidence for transgene expression was obtained in tissues from transgenic fry, despite an obvious increase in size relative to control siblings, suggesting very low levels of transgene expression early in development. GH mRNA levels (per microg RNA) were also examined in the pituitary gland, and were found to be significantly lower (P < 0.01) in transgenic coho compared to nontransgenic animals of the same size. Pituitary glands of transgenic animals were also smaller than control animals of the same size, and pituitary size, expressed as a proportion of body weight, decreased with body size in transgenic but not control animals. These results imply that pituitary GH expression is regulated by negative feed-back controls as occurs in other vertebrate systems. GH mRNA was examined in pituitary glands by whole-mount in situ hybridization, and, whereas overall levels appeared reduced in transgenic animals, the site of hybridization did not differ between transgenic and control glands.
Mol Cell Endocrinol 1999 Mar 25
PMID:Transgene and host growth hormone gene expression in pituitary and nonpituitary tissues of normal and growth hormone transgenic salmon. 1037 25

Growth hormone (GH) gene expression has been reported in the mammary glands of various mammalian species. The mechanism by which the GH gene becomes activated in extrapituitary tissues is currently unclear. We have characterized the canine mammary and pituitary GH gene transcripts by Northern blot, 5'- and 3'-RACE (rapid amplification of cDNA ends), and DNA sequence analysis. Northern blot analysis detected GH gene transcripts in mammary glands of dogs which were exposed to high levels of progestins. The mammary and pituitary GH cDNAs were shown to be identical in both the coding region and untranslated regions. Pituitary GH gene expression is highly dependent upon the transcription factor Pit-1. Analysis of Pit-1 gene expression using RT-PCR followed by Southern hybridization revealed a strong pituitary signal but faint, weak or no hybridization signals in mammary gland samples. Among the negative samples were progestin-treated dogs with high mammary GH gene expression. These findings indicate that mammary and pituitary GH gene transcripts originate from the same transcription start site but are regulated differentially.
Mol Cell Endocrinol 1999 Apr 25
PMID:Canine mammary growth hormone gene transcription initiates at the pituitary-specific start site in the absence of Pit-1. 1041 6

Pituitary adenylyl cyclase activating polypeptide (PACAP-27), forskoline and carbachol increased type A atrial natriuretic peptide receptor (NPR-A) density, as well as NPR-A mRNA level, in the human neuroblastoma NB-OK-1 cell line. TPA did not have any effect per se, but blunted the effect of PACAP-27 on both NPR-A density and NPR-A mRNA. The half-life of the NPR-A mRNA was not modified by any of the agents tested. Our data support an original transcriptional upregulation of human NPR-A in response to cAMP-induced agents, and in response to carbachol.
Mol Cell Endocrinol 1999 Apr 25
PMID:Human A-type ANP receptor upregulation by PACAP and carbachol in neuroblastoma cells. 1041 13

Pituitary adenylate cyclase activating polypeptide (PACAP) was isolated from ovine hypothalamus and known to stimulate the production of cAMP in anterior pituitary cells. In the recent report, the expression of PACAP was detected in preovulatory follicles, and treatment with PACAP stimulated the production of progesterone and prostaglandin E(2) through the action of AC and PLC pathways in the ovary. PACAP binds to three type receptors. Type I A receptor is coupled to adenylate cyclase (AC) and phospholipase C (PLC) pathways, while type I B and type II receptors are only coupled to AC. Thus, the present study aimed to evaluate the temporal expression of PACAP and its type I A receptor mRNAs in the rat ovary after treatment with pregnant mare's serum gonadotropin and human chorionic gonadotropin (hCG). Northern blot analysis showed that PACAP transcripts were transiently expressed from 3-9 hr after hCG treatment, reaching a maximum at 6 hr. During these time points, PACAP mRNAs were specifically and strongly expressed in granulosa cells and cumulus cells of large preovulatory follicles and interstitial glandular cells. Type I A receptor mRNAs were also transiently expressed in granulosa cells of large preovulatory follicles from 3-9 hr after hCG treatment. PACAP and its type I A receptor mRNAs were expressed in the same preovulatory follicles. These results demonstrate that PACAP acts as an autoregulator or pararegulator through type I A receptor in granulosa cells and cumulus cells of large preovulatory follicles. Thus, we suggest that PACAP may have a critical role in granulosa cells of preovulatory follicles for the preparation of ovulation.
Mol Reprod Dev 2000 Apr
PMID:Expression of pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP type I A receptor mRNAs in granulosa cells of preovulatory follicles of the rat ovary. 1069 44

These studies examined the importance of phospholipase Cbeta (PLCbeta) in the calcium responses of pituitary cells using PLCbeta3 knockout mice. Pituitary tissue from wild-type mice contained PLCbeta1 and PLCbeta3 but not PLCbeta2 or PLCbeta4. Both Galphaq/11 and Gbetagamma can activate PLCbeta3, whereas only Galphaq/11 activates PLCss1 effectively. In knockout mice, PLCbeta3 was absent, PLCbeta1 was not up-regulated, and PLCbeta2 and PLCbeta4 were not expressed. Since somatostatin inhibited influx of extracellular calcium in pituitary cells from wild-type and PLCbeta3 knockout mice, the somatostatin signal pathway was intact. However, somatostatin failed to increase intracellular calcium in pituitary cells from either wild-type or knockout mice under a variety of conditions, indicating that it did not stimulate PLCbeta3. In contrast, somatostatin increased intracellular calcium in aortic smooth muscle cells from wild-type mice, although it evoked no calcium response in cells from PLCbeta3 knockout animals These results show that somatostatin, like other Gi/Go-linked hormones, can stimulate a calcium transient by activating PLCbeta3 through Gbetagamma, but this response does not normally occur in pituitary cells. The densities of Gi and Go, as well as the relative concentrations of PLCbeta1 and PLCbeta3, were similar in cells that responded to somatostatin with an increase in calcium and pituitary cells. Calcium responses to 1 nM and 1 microM TRH and GnRH were identical in pituitary cells from wild-type and PLCbeta3 knockout mice, as were responses to other Gq-linked agonists. These results show that in pituitary cells, PLCbeta1 is sufficient to transmit signals from Gq-coupled hormones, whereas PLCbeta3 is required for the calcium-mobilizing actions of somatostatin observed in smooth muscle cells.
Mol Endocrinol 2001 Jan
PMID:Calcium responses to thyrotropin-releasing hormone, gonadotropin-releasing hormone and somatostatin in phospholipase css3 knockout mice. 1114 44

Inhibin binding protein (InhBP) and the transforming growth factor-beta (TGF beta) type III receptor, beta glycan, have been identified as putative inhibin coreceptors. Here we cloned the InhBP cDNA in rats and predict that it encodes a large membrane-spanning protein that is part of the Ig superfamily, as has been described for humans. Two abundant InhBP transcripts (4.4 and 1.8 kb) were detected in the adult rat pituitary. The larger transcript encodes the full-length protein while the 1.8-kb transcript (InhBP-short or InhBP-S) corresponds to a splice variant of the receptor. This truncated isoform contains only the N-terminal signal peptide and first two (of 12) Ig-like domains observed in the full-length InhBP (InhBP-long or InhBP-L). InhBP-S does not contain a transmembrane domain and is predicted to be a soluble protein. Beta glycan was also detected in the pituitary; however, it was most abundant within the intermediate lobe. Although we also observed beta glycan immunopositive cells in the anterior pituitary, they rarely colocalized with FSH beta-producing cells. We next examined physiological regulation of the coreceptors across the rat estrous cycle. Like circulating inhibin A and inhibin B levels, pituitary InhBP-L and InhBP-S mRNA levels were dynamically regulated across the cycle and were negatively correlated with serum FSH levels. Expression of both forms of InhBP was also positively correlated with serum inhibin B, but not inhibin A, levels. These data are particularly interesting in light of our in vitro observations that InhBP may function as an inhibin B-specific coreceptor. Pituitary beta glycan mRNA levels did not fluctuate across the cycle nor did they correlate with serum FSH. These observations, coupled with its pattern of expression within the pituitary, indicate that beta glycan likely functions as more than merely an inhibin coreceptor within the pituitary. A direct role for InhBP or beta glycan in regulation of pituitary FSH by inhibin in vivo has yet to be determined, but the demonstration of dynamic regulation of pituitary InhBP and its negative relation to serum FSH across the estrous cycle is an important step in this direction.
Mol Endocrinol 2001 Apr
PMID:Inhibin binding protein in rats: alternative transcripts and regulation in the pituitary across the estrous cycle. 1126 15

Changes in the perinatal testosterone surge have been related to demasculinization of the central nervous system and androgen-dependent growth of the reproductive organs in male mammals. Earlier reports suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with androgen production, but the perinatal effects have remained elusive. In the present study we explored in utero-effects of TCDD (0.05, 0.1, 0.5, and 1.0 microg/kg), introduced on day 13.5 of pregnancy, on prenatal (day 19.5 post-conception [p.c.]) testosterone (T) surge and pituitary luteinizing hormone (LH) production in TCDD-resistant Han/Wistar (H/W) and TCDD-sensitive Long-Evans (L-E) rats. To elucidate estrogenic effects on T and LH production, Sprague-Dawley (S-D) fetuses with previously known DES-sensitivity were exposed in utero to diethylstilbestrol (DES, 100-300 microg/kg) on days 13.5, 15.5, and 17.5 p.c. For comparison, H/W fetuses that responded to TCDD treatments were exposed to DES at concentration of 100 microg/kg. It was found that TCDD has a stimulatory effect on testicular T synthesis in the H/W fetuses and that their circulating T concentrations increased significantly. The effect was not seen in the inbred L-E fetuses, which throughout the study showed considerably low testicular T levels. Pituitary LH concentrations also increased in the H/W fetuses exposed to TCDD. Effects of TCDD (1.0 microg/kg) in the H/W fetuses could be confirmed in vitro by human chorionic gonadotropin (hCG) stimulation assay showing the highest response rate in the TCDD exposed testes. Stimulation of cyclic AMP (adenosine-3', 5'-cyclic monophosphate[cAMP]) production was not considerably altered by in utero TCDD exposure. A significant depression in testicular and plasma T content was seen in the DES-exposed S-D and H/W fetuses, but pituitary LH levels did not alter considerably. In the presence of hCG, DES-exposed testes showed lower in vitro T and cAMP production rates compared to the untreated testes. TCDD (1.0 microg/kg) increased and DES decreased the male body weight gain, but the changes were not sex-dependent. It is concluded that TCDD may increase the amplitude of the prenatal testosterone surge in male rats by stimulating pituitary LH production and enhancing the sensitivity of the fetal testis to LH. DES, on the contrary, apparently impairs testicular steroidogenesis and pituitary function.
Mol Cell Endocrinol 2001 Jun 10
PMID:Prenatal testosterone and luteinizing hormone levels in male rats exposed during pregnancy to 2,3,7,8-tetrachlorodibenzo-p-dioxin and diethylstilbestrol. 1140 7

Compelling evidence suggests that a regulatory loop between leptin and the hypothalamo-pituitary-adrenal (HPA) axis is operative, where ACTH inhibits leptin secretion by adipose tissue and in turn leptin increases expression and secretion of ACTH. However, conflicting findings have been obtained in vivo on the acute and chronic effects of leptin on the HPA axis. Adult female Wistar rats, kept in metabolic cages, were intraperitoneally infused for 2, 4, 8 or 16 days with leptin (10 nmol/kg. 24 h); control animals were infused with the vehicle only. The rate of body-weight gain was similar in control and leptin-infused rats. At day 16 of treatment relative pituitary weight was higher and relative adrenal weight smaller in leptin-infused than control rats. Pituitary ACTH concentration gradually decreased with the duration of treatment, and the drop was significantly higher in leptin-infused than control rats. During the entire experimental period the blood level of aldosterone was similar in both groups of rats. Conversely, at days 2 and 4 of treatment the blood concentration of corticosterone was lower in leptin-infused than in control rats, which at these times displayed elevated levels of circulating corticosterone. Taken together, these findings allow us to conclude that in the rat the prolonged infusion of low doses of leptin i) primarily depresses pituitary ACTH production, the effect being probably mediated by the hypothalamus; and ii) inhibits corticosterone response to the stress evoked by placing of animals in the metabolic cages.
Int J Mol Med 2002 Jan
PMID:Effects of prolonged leptin infusion on rat pituitary-adrenocortical function. 1174 98

The effects of a vasoactive intestinal peptide (VIP) receptor antagonist (VIPhyb) on human glioblastoma cells were characterized. Pituitary adenylate cyclase activating polypeptide (125I-PACAP-27) bound with high affinity to U87, U118, and U373 cells. Specific 125I-PACAP-27 binding to U87 cells was inhibited, with high affinity, by PACAP but not VIP or VIPhyb (IC50 = 10, 1500, and 500 nM, respectively). By reverse transcriptase-polymerase chain reaction (RT-PCR), a major 305 bp band was observed indicative of PAC1 receptors. PACAP-27 caused cAMP elevation and the increase in cAMP caused by PACAP-27, was inhibited by the VIPhyb. Also, PACAP-27 caused cytosolic Ca2+ elevation in Fura-2AM loaded U87 cells and the VIPhyb inhibited this increase. Using the MTT growth assay, the VIPhyb was shown to inhibit glioblastoma growth in a concentration-dependent manner. Using a clonogenic assay in vitro, 10 microM VIPhyb significantly inhibited proliferation of U87, U118, and U373 cells. In vivo, 0.4 microg/kg VIPhyb inhibited U87 xenograft proliferation in nude mice. These results suggest that the VIPhyb antagonizes PAC1 receptors on glioblastoma cells and inhibits their proliferation.
J Mol Neurosci 2001 Dec
PMID:A vasoactive intestinal peptide antagonist inhibits the growth of glioblastoma cells. 1185 29


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