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)

To determine the rat PRL (rPRL) promoter sequences that mediate pituitary-specific and cAMP-induced gene expression in vivo, various lengths of the rPRL promoter were ligated to the luciferase reporter gene and introduced into pituitary and non-pituitary cell lines. A 30-fold increase in rPRL promoter activity was observed in GH4 rat pituitary tumor cells compared to nonpituitary Rat2 fibroblast and HeLa cervical carcinoma cells. About 45% of this cell-specific promoter activity was competed by a plasmid containing the -67 to -45 rPRL promoter region, which is the most proximal binding site for a lactotroph-specific factor. Compared to a -425 rPRL construct, transfection with rPRL 5'-end points of -212, -178, and -127 contained 23%, 45%, and 1%, respectively, of luciferase activity. Forskolin stimulation resulted in a 10-fold induction of all the rPRL promoter fragments tested. Of note, a -127 deletion which was devoid of any basal promoter activity was also induced 10-fold by forskolin. The forskolin effect was abolished when GH4 rat pituitary cells were cotransfected with a plasmid encoding a protein kinase A inhibitor, indicating protein kinase A is involved in the activation mechanism. These data document that both positive and negative effectors influence basal rPRL promoter activity. Furthermore, the minimum sequences required for pituitary-specific rPRL promoter activity are altered by intracellular cAMP levels. Taken together, the data indicate that hormone-activated and cell-specific factors may interact to establish a particular setpoint for rPRL gene expression.
Mol Endocrinol 1989 May
PMID:Analysis of rat prolactin promoter sequences that mediate pituitary-specific and 3',5'-cyclic adenosine monophosphate-regulated gene expression in vivo. 254 56

Pharmacological agents are widely used to probe the mechanism of action of TRH. A number of these drugs behave as local anesthetics at high concentrations. The effect of local anesthetics on the binding of [3H]Me-TRH to specific receptors was studied using the GH4C1 line of rat pituitary tumor cells. [3H]Me-TRH binding was inhibited by classical local anesthetics with the order of potency (IC50 values): dibucaine (0.37 mM) greater than tetracaine (1.2 mM) greater than lidocaine (3.3 mM) greater than procaine and benzocaine (greater than 10 mM). IC50 values for other drugs with local anesthetic properties that inhibited [3H]Me-TRH were: 100 microM trifluoperazine, 100 microM imipramine, 170 microM chlorpromazine, 300 microM verapamil, and 700 microM propranolol. Inhibition by tetracaine and verapamil increased as the pH was raised from 6 to 8.5, indicating that the free base form of the amine drugs was the inhibitory species, and the local anesthetic effect was greater at 37 C than at 24 C or 0 C. [3H]Me-TRH binding to receptors in isolated membranes was inhibited to the same extent as binding to receptors on intact cells. Local anesthetics were 3- to 20-fold less potent at inhibiting [3H]Me-TRH to digitonin-solubilized receptors than binding to intact cells. In contrast, the potency of chlordiazepoxide, a putative TRH antagonist, to inhibit [3H]Me-TRH binding was equal using cells and solubilized receptors (IC50 = 10 microM). Local anesthetics inhibited TRH-stimulated PRL release and also inhibited basal PRL secretion and secretion stimulated by two nonhormonal secretagogues, (Bu)2cAMP and a phorbol ester.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Sep
PMID:Pituitary thyrotropin-releasing hormone receptors: local anesthetic effects on binding and responses. 255 7

Human PRL receptor cDNA clones from hepatoma (Hep G2) and breast cancer (T-47D) libraries were isolated by using a rat PRL receptor cDNA probe. The nucleotide sequence predicts a mature protein of 598 amino acids with a much longer cytoplasmic domain than the rat liver PRL receptor. Although this extended region has additional segments of localized sequence identity with the human GH receptor, there is no identity with any consensus sequences known to be involved in hormonal signal transduction. This cDNA will be a valuable tool to better understand the role of PRL in the development and growth of human breast cancer.
Mol Endocrinol 1989 Sep
PMID:Identification of a cDNA encoding a long form of prolactin receptor in human hepatoma and breast cancer cells. 255 9

Mutant forms of mouse placental lactogen-II (PL-II) have been generated to assess the role of specific amino acid residues and protein regions in binding to the PRL receptor and in mitogenic activity. Conversion of any of three lactogen-specific residues significantly reduced both of these hormone functions; mutation of the two other lactogen-specific amino acids revealed only minimal effects unless these changes were coupled with a second mutation. Deletions within the PL-II protein all resulted in a complete loss of function, but switching regions between PL-II and proliferin, another member of the prolactin family in the mouse, did yield a chimeric protein with some PRL-like activity. This activity was increased substantially by conversion of one amino acid residue in the proliferin region to the corresponding lactogen-specific residue. The locations of the amino acids that have been found to affect hormone function are predicted to be closely apposed in the folded protein, suggesting that this region may be the site of interaction of this lactogenic hormone with the PRL receptor.
Mol Endocrinol 1989 Dec
PMID:Mutational analysis of a lactogenic hormone reveals a role for lactogen-specific amino acid residues in receptor binding and mitogenic activity. 256 Aug 6

Expression of the SRIH gene was investigated in six human normal anterior pituitaries, six GH-, three PRL-, three mixed GH/PRL-secreting and four nonsecreting adenomas. Total cellular RNA and poly(A+) mRNAs were analyzed by dot and Northern blot hybridization to a 3'-end labeled oligonucleotide probe specific for the human pre-proSRIH mRNA. A weak but detectable pre-proSRIH hybridization signal was present in human normal anterior pituitaries and in the four groups of adenomas. The size of this pre-proSRIH mRNA was indistinguishable from that found in our hypothalamic samples and close to that described in the literature. The wide variation of the signal intensity from one case to the other in each group of the different types of normal and tumoral antehypophyseal samples prevented establishment of any correlation between the level of pre-proSRIH mRNA and the nature of the pituitary tissue. The presence of SRIH mRNA in human normal and tumoral anterior pituitary tissues provides a sound basis to substantiate the hypothesis of a SRIH biosynthesis in the human anterior pituitary gland.
Mol Endocrinol 1989 Aug
PMID:Evidence of pre-prosomatostatin mRNA in human normal and tumoral anterior pituitary gland. 257 Oct 81

After 60% hepatectomy in rats, prolactin secreting cells (PRL-cells) and growth hormone secreting cells (GH-cells) of the anterior pituitary gland were distinctly identified by the protein A-gold procedure combined with electron microscopy. The animals were sacrificed by the decapitation at midnight at intervals of about 28, 76 and 124 h after the operation. The principal changes can be summarized as follows; (1) Hypertrophy of the Golgi complex, (2) Dilation of the rough endoplasmic reticulum (RER), (3) Increased numbers of secretory granules (markedly in GH-cells), and occurrence of granule extrusion or exocytosis, (4) Increased numbers of lysosomes, which were mostly seen at 124 h after the operation. These ultrastructural changes were remarkably observed in both PRL and GH-cells. Especially, the noticeable changes in PRL-cells after partial hepatectomy in the rat were new findings in this study. The above results suggest that hepatectomy induced synthesis and release of GH and PRL in cells from pars distalis.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Electron microscopic immunocytochemistry of prolactin secreting cells (PRL-cells) and growth hormone secreting cells (GH-cells) in the anterior pituitary gland of partially hepatectomized rats. 257 99

Transient expression experiments, using chimeric plasmids containing 3000 base pairs of PRL 5'-flanking sequences linked to the bacterial chloramphenicol acetyl transferase structural gene, demonstrate that L-T3 can inhibit (GH1 cells) or stimulate (GH4C1 cells) chloramphenicol acetyl transferase activity. Deletion experiments have defined the region necessary for these effects to sequences between -176 and -11 of the PRL gene. This region seems to contain the sequences necessary both for basal expression and for L-T3 regulation. Gel mobility shift experiments revealed that proteins extracted from GH1 and GH4C1 cell nuclei but not rat-2 fibroblasts interact with the PRL gene from -176 to +75. DNase I footprinting studies reveal two footprints which are the same in all pituitary derived cells tested. These footprints are not seen in rat-2 fibroblasts. Neither of these footprints likely represents binding of the L-T3-receptor since extracts from cells containing very low levels of receptor form footprints identical to those from cells with an abundance of receptors. These results suggest that different trans-acting factors, not identifiable by conventional footprinting techniques, are present in these cell lines which account for their opposite responses to L-T3. The regulation of PRL gene expression by L-T3 is unique in that both stimulation and suppression can be demonstrated using a single hormone-gene system. This should allow us to answer fundamental questions regarding the molecular switch between stimulation and suppression of gene expression by hormones.
Mol Endocrinol 1989 Oct
PMID:Transcriptional regulation of prolactin gene expression by thyroid hormone--alternate suppression and stimulation in different GH cell lines. 260 52

Sequence analysis of cDNA for hamster placental lactogen-II (PL-II) revealed that while this protein has a high degree of sequence homology to mouse and rat PL-II it contains a pair of cysteine residues not present in the mouse and rat proteins or in any other known member of the GH-PRL-PL protein family. This unique pair of cysteine residues may be responsible for the extreme tendency of hamster PL-II, compared to other members of the GH-PRL-PL family, to form disulfide-bonded hormone-serum protein complexes.
Mol Endocrinol 1989 Nov
PMID:Hamster placental lactogen-II contains a structural feature unique among the growth hormone-prolactin-placental lactogen family. 260 54

During lactation, a dramatic rise in serum PRL stimulates milk production, resulting in a substantial rise in calcium mobilization from gut and bone. We found that the production of a newly characterized calcium-mobilizing PTH-like peptide (PTH-LP) by mammary tissue was tightly linked to lactation, suggesting a possible role for PRL in the expression of PTH-LP. Here it is shown that suckling results in both an elevation in serum PRL and the appearance of PTH-LP mRNA in mammary tissue. Bromocriptine, a potent inhibitor of PRL secretion, blocked the suckling-associated rise in serum PRL and the subsequent induction of PTH-LP mRNA in mammary gland. Furthermore, injection of PRL dramatically induced PTH-LP mRNA in unsuckled puerperal glands, but not in glands on day 21 of pregnancy. Thus, the correlation between serum levels of PRL and the expression of PTH-LP mRNA in mammary tissue extends the role of PRL in milk production and suggests a possible mechanism for the PRL effects on calcium metabolism.
Mol Endocrinol 1989 Sep
PMID:The mRNA encoding a parathyroid hormone-like peptide is produced in mammary tissue in response to elevations in serum prolactin. 260 67

Ovine placental lactogen (oPL) is active in a wide range of GH and PRL assays, a property that it shares with human GH (hGH). In addition, oPL is one of a small number of hormones that bind the human GH receptor with high affinity. In order to compare the sequence of oPL to the sequences of other members of the GH family, full-length cDNA clones have been isolated. These clones predict that the full sequence of oPL contains 198 amino acids preceded by a 38 amino acid signal sequence. The mature oPL sequence includes six cysteine and two tryptophan residues and shows substantially more identity to bovine PL (67%) and oPL (49%) than to mouse (31%) or human (25%) PL or to oGH (28%) or (26%) hGH. Like the natural hormone, oPL expressed in mammalian tissue cells binds with high affinity to a soluble form of the recombinant hGH receptor. Thus, oPL binds to the human receptor in spite of having a sequence that is considerably divergent from hGH. Interestingly, the sequence of oPL differs from hGH at most of the amino acids recently found by mutagenesis studies to be important residues in the binding of hGH to the human receptor.
Mol Endocrinol 1989 Sep
PMID:Cloning and expression of ovine placental lactogen. 260 69


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