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)

Pituitary GH3 cells were transfected with different deletion mutants of the human prolactin (hPRL) promoter fused to the CAT reporter gene. The proximal region (-250 to -42) was sufficient to confer stimulation by both thyrotropin-releasing hormone (TRH) and epidermal growth factor (EGF). Further deletion analyses demonstrated the importance of the three proximal Pit-1 binding sites in this response. However, Pit-1 binding oligonucleotides confer neither TRH nor EGF induction to a linked neutral promoter, suggesting that other elements might be involved. We have previously shown that sequence A (-115 to -85) is needed together with Pit-1 binding sites for full cyclic AMP response of hPRL-CAT. Mutation of this sequence strongly affects TRH and EGF induction. On the other hand, three copies of sequence A confer both TRH and EGF response to a linked neutral promoter. In conclusion, although TRH and EGF activate mostly different intracellular pathways, they mediate transcriptional induction of the hPRL promoter via identical cis elements.
Mol Cell Endocrinol 1993 Mar
PMID:Thyrotropin-releasing hormone and epidermal growth factor induce human prolactin expression via identical multiple cis elements. 838 15

Pituitary cultures from adult rats contain two subtypes of prolactin (PRL) cells, small-plaque (SP) and large-plaque (LP) lactotropes, which exhibit distinct rates of basal secretion and thereby form PRL plaques of different sizes in reverse hemolytic plaque assay experiments. In the present study, we have used plaque assays to examine the effects of omega-conotoxin (omega-CgTx) and nifedipine, which block Ca2+ entry through high voltage-activated (HVA) channels in the plasma membrane, on basal PRL secretion from single male rat lactotropes. We found that omega-CgTx, like nifedipine, is a potent inhibitor of PRL secretion. In addition, we observed that both drugs decrease the number of cells forming large PRL plaques, while promoting a comparable increase in the abundance of small plaque formers. The results indicate that blocking the HVA Ca channels preferentially suppresses PRL release from LP lactotropes, and suggest that the inhibited PRL secretors tend to behave functionally as SP lactotropes.
Mol Cell Endocrinol 1993 Apr
PMID:Lactotrope subtypes are differentially responsive to calcium channel blockers. 839 90

Studies were conducted in vitro and in vivo to determine whether or not inhibin affects the transcription rate of the gene for the beta subunit of follicle stimulating hormone (FSH beta). Pituitary cells in primary culture were incubated with 0-3000 milli-units/ml inhibin; a dose-related decrement in mRNA was obtained but a parallel effect was not observed for the transcription rate of the FSH beta gene in a nuclear run-on experiment. To determine effects in vivo, ovariectomized ewes were treated with saline (group 1), 75 micrograms inhibin 6 h before slaughter (group 2), inhibin 6 h and 12 h before slaughter (group 3) or inhibin 12 h before slaughter (group 4). In samples taken each 2 h, plasma FSH levels were seen to be maximally reduced 6 h after a single injection of inhibin; at this time mRNA levels were reduced up to 100% whereas FSH beta gene transcription rate was reduced by 50%. A second injection at 6 h (group 3) caused a further reduction in plasma FSH levels with no additional effect on transcription rate. In those sheep killed 12 h after a single inhibin injection, transcription rate for the FSH beta gene, cytoplasmic mRNA levels and plasma FSH concentrations had recovered. These studies show that the rapid effect of inhibin on FSH beta mRNA levels may be due, in part, to an effect on transcription rate of the FSH beta gene. An additional mechanism is required, however, to fully explain the inhibin effect on FSH beta mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 Feb
PMID:Transcription rate of the follicle stimulating hormone (FSH) beta subunit gene is reduced by inhibin in sheep but this does not fully explain the decrease in mRNA. 847 50

We report here that cytochrome P4501A1 in the male rainbow trout pituitary is highly inducible by beta-naphthoflavone. Pituitary cells containing inducible P4501A1 were identified by double immunostaining as gonadotrophs containing gonadotropin II. Thus, the pituitary gonadotrophs may be target cells for polyaromatic hydrocarbons. Elevated plasma levels of gonadotropin II (GTH II) and testosterone in the induced fish indicated that the functioning of the pituitary was disturbed. Because GTH II regulate the final stage of sexual maturation the results implies that exposure to P4501A1 inducing compounds may disturb this development stage.
Mol Cell Endocrinol 1993 Feb
PMID:Pituitary as a target organ for toxic effects of P4501A1 inducing chemicals. 847 59

Pituitary adenylate cyclase activating polypeptide (PACAP) increases glycoprotein hormone alpha-subunit mRNA levels suggesting a role for PACAP in maintaining the high levels of alpha-subunit protein characteristic of the pituitary. The present study used primary pituitary cell cultures and the alpha T3-1 pituitary cell line to investigate how PACAP affects alpha-subunit mRNA transcripts. Stimulation of cultured pituitary cells with 10 nM PACAP38, 10 nM GnRH, or the combination, for 24 h increased alpha-subunit mRNA levels 1.5-fold, whereas GnRH more effectively (P<0.01) stimulated alpha-subunit protein release than did PACAP38 (3.2- vs. 2.0-fold). alpha-Subunit mRNA levels in alphaT3-1 cells were also increased by PACAP38 and by GnRH to maximum values at 12 h (P<0.05), and alpha-subunit protein secretion rose proportionately and in parallel with alpha-subunit mRNA levels. PACAP38 was a 100-fold more potent stimulator of alpha-subunit mRNA than was VIP, and a VIP-antagonist failed to block the stimulatory effect of PACAP38, suggesting an effect via type PACAP 1 receptors. Type I receptor mRNA transcripts were identified by Northern analysis in alphaT3-1 cells. Depletion of PCK activity by PMA failed to block the stimulatory effect of PACAP38, but prevented GnRH from increasing alpha-subunit mRNA levels and alpha-subunit secretion. PACAP38, like 8Br-cAMP and forskolin, stimulated (P<0.05) luciferase (LUC) activity in alphaT3-1 cells transfected with a plasmid containing the first 846 of 180 base pairs of the 5'-flanking region of the human alpha-subunit gene linked upstream to a LUC reporter gene. Finally, experiments using the transcription inhibitor DRB reveal that PACAP does not appreciably change alpha-subunit mRNA half-life. These findings are consistent with the proposal that PACAP contributes to the high levels of alpha-subunit protein characteristic of the pituitary by activating Type I receptors and stimulating alpha-subunit gene transcription in part by the cAMP/PKA pathway.
Mol Cell Endocrinol 1995 Sep 22
PMID:Regulation of alpha-subunit mRNA transcripts by pituitary adenylate cyclase-activating polypeptide (PACAP) in pituitary cell cultures and alpha T3-1 cells. 867 19

Following the cleavage of peptide precursors by endopeptidases such as the proprotein convertases PC2 and PC3, carboxypeptidase E (CPE) functions to remove basic amino adds from the C-terminus of various pituitary hormones. We investigated the role of CPE in the differential sensitivity between rat strains to estrogen-induced pituitary tumors. Pituitary CPE protein levels were unchanged by diethylstilbestrol (DES) in tumor-resistant Sprague-Dawley (SD) rats. However, in tumor-susceptible Fischer 344 (F344) rats, DES decreased CPE protein levels such that by 7 and 8 weeks of treatment, CPE was barely detectable. One week withdrawal of DES caused an increase in CPE protein levels at 8 weeks. After 2 and 4 weeks of DES treatment, CPE protein levels in F344 rats decreased to 18 and 2.3% of control values, respectively, but no strain difference was observed in the protein levels of proprotein convertase 2 (PC2) or PC3. Additionally, Brown Norway (BN), F344, and F1 hybrid (BN x F344) rats were treated with DES for 10 weeks. The level of pituitary CPE protein was not affected by DES in BN rats whereas F344 rats had only 8% of the level of CPE pituitary protein of BN rats. The pituitaries of F1 rats, which had an intermediate weight response to DES, had an intermediate level of CPE protein (31% that of BN rats). Levels of CPE mRNA were not affected by DES in SD rats while in F344 rats DES tended to decrease levels of CPE mRNA after both 2 and 4 weeks of treatment, although the response was variable. It thus appears that pituitary CPE protein is differentially regulated by DES between tumor-resistant rats and F344 rats primarily at the post-transcriptional level. Furthermore, in F344 rats, levels of CPE protein are inversely correlated to increases in pituitary weight caused by DES treatment.
Mol Cell Endocrinol 1996 Mar 25
PMID:Decreased expression of carboxypeptidase E protein is correlated to estrogen-induction of rat pituitary tumors. 873 83

Pituitary adenylate cyclase-activating peptide (PACAP) is a 38-amino acid polypeptide, first isolated from ovine hypothalamus, which directly stimulates the release of several pituitary hormones, including GH, ACTH, and LH. The presence of PACAP receptors in several brain areas, including the hypothalamus, suggests that this peptide might play a role as neurotransmitter/neuromodulator. We have thus investigated the effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) injections of PACAP and the potent PACAP antagonist PACAP(6-38) on gonadotropin-releasing hormone (GnRH) and somatostatin (SS) gene expression in the male rat hypothalamus. The levels of mRNA were measured at the cellular level by quantitative in-situ hybridization. The i.c.v. injection of PACAP produced a 12.5% increase in the GnRH mRNA levels, an effect which was completely prevented by the concomitant administration of the PACAP antagonist. The administration of the PACAP antagonist induced by itself a 12.9% decrease in the hybridization signal. The i.v. administration of the same peptides induced modifications in GnRH gene expression which were completely opposite to those produced by i.c.v. administration. In somatostatinergic neurons located in the periventricular nucleus, the i.c.v. injection of the peptides induced modification in SS gene expression which were very similar to those observed for GnRH gene expression, although the changes were less striking. The i.v. administration of PACAP or its antagonist did not induce any change in the levels of SS mRNA. These results then strongly suggest that PACAP might be involved in a positive regulation of two neuropeptides involved in the control of anterior pituitary secretion via central specific receptors. The inverse influence of PACAP on GnRH gene expression after the i.v. injection might be explained by the short feedback effect induced by the direct stimulation of gonadotropin hormone release following the systemic injection of the peptide.
Brain Res Mol Brain Res 1996 Sep 05
PMID:Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on gonadotropin-releasing hormone and somatostatin gene expression in the rat brain. 888 47

Pituitary function is regulated by hypothalamic releasing hormones secreted into hypophyseal-portal blood. A new hypothesis is that pituitary function might also be regulated at the local level by releasing hormones synthesized within the pituitary. Here we show that the pituitary expresses high levels of the gene encoding for urocortin. We suggest that urocortin synthesized by the pituitary may modulate pituitary function, and that adrenocorticotropic hormone (ACTH) secretion is dependent on input not only from the hypothalamus as previously described, but it may also be regulated by urocortin synthesized locally. Urocortin binds to the corticotropin-releasing hormone (CRH) receptor type 1 (CRH-R1) with high affinity and potently stimulates pituitary-adrenal function. Our group and others have previously localized high levels of CRH-R1 mRNA in the pituitary. Using a 35S-labeled rat urocortin riboprobe we have now localized urocortin mRNA in rat brain and pituitary. The finding of urocortin gene expression in the pituitary may help explain why proopiomelanocortin (POMC) mRNA levels are not decreased during hypothalamo-pituitary disconnection, and also describes a new level of complexity in the regulation of hypothalamo-pituitary function. Future studies should consider the possibility that pituitary function might be regulated at the local level by urocortin.
Mol Psychiatry 1996 Sep
PMID:Localization of urocortin messenger RNA in rat brain and pituitary. 911 53

Pituitary-specific transcription of the evolutionarily related rat (r) GH and PRL genes involves synergistic interactions between Pit-1 and other promoter-binding factors including nuclear receptors. We show that Pit-1/thyroid hormone receptor (TR) and Pit-1/estrogen receptor (ER) synergistic activation of the rGH and rPRL promoters are globally similar. Both synergies depend upon the same activation functions in Pit-1 and also require activation function-2 conserved in TR and ER. The activation function-2 binding protein, RIP140, previously thought to be a nuclear receptor coactivator, strongly inhibits both Pit-1/TR and Pit-1/ER synergy. RIP140 inhibition is profoundly influenced, in a promoter-specific fashion, by a synergism-selective function in Pit-1: deletion of Pit-1 amino acids 72-100 switches RIP140 to an activator of Pit-1/ER and Pit-1/TR synergy at the rPRL promoter but not at the rGH promoter. Pit-1 amino acids 101-125 are required for RIP140 inhibition or activation again only at the rPRL promoter. Therefore, functions within one factor can determine the activity of a coactivator binding to its synergistic partner. This promoter context-specific synergistic interplay between transcription factors and coactivators is likely an essential determinant of cell-specific transcriptional regulation.
Mol Endocrinol 1997 Aug
PMID:Activities in Pit-1 determine whether receptor interacting protein 140 activates or inhibits Pit-1/nuclear receptor transcriptional synergy. 925 23

Pituitary follitropin (FSH) has pleiotropic actions on gonads, but it is not certain if all these events are mediated by a single receptor. A single gene for the FSH receptor undergoes extensive alternate splicing generating multiple transcripts, and several of these have been cloned and characterized from the sheep testis. In this study we have investigated the expression in HEK (human embryonic kidney) 293 cells of a cloned cDNA encoding the first eight exons of the FSH receptor along with a carboxyterminal extension that contributed a hypothetical single transmembrane domain. This cDNA, which lacked the conventional seven transmembrane motif of the full-length 695 residue wild-type receptor protein, was also efficiently expressed on the cell surface and exhibited high affinity and specificity for FSH binding. LH did not compete for FSH binding indicating that these structures contained all the motifs necessary for specific hormone recognition. Following hormone binding and affinity crosslinking the deduced M(r) of the expressed receptor was compatible with dimer formation. The expression of these altered FSH receptors on the cell surface was confirmed by immunohistochemistry, which revealed punctate labeling in a pattern comparable to that shown by cells transfected by wild-type receptor cDNA. Addition of FSH stimulated 3H-thymidine incorporation in transfected cells in a biphasic manner. By performing RT-PCR we could show that similar altered receptor transcripts were present in both the ovary and testis. Our results reveal for the first time that the seven transmembrane structure of FSH-receptor is not absolutely necessary for cell surface expression and hormone binding provided other compensating motifs are present in the protein structure for membrane insertion. Some of these features are typical of growth factor receptors. Our investigations also demonstrate that alternate splicing of the FSH receptor gene provides a mechanism for creating receptor diversity and suggest that multiple receptors could be involved in regulation of hormone action.
Mol Reprod Dev 1997 Dec
PMID:Alternative splicing converts the G-protein coupled follitropin receptor gene into a growth factor type I receptor: implications for pleiotropic actions of the hormone. 936 41


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