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

The activity of some glycolytic, oxidative, and degradative enzymes was studied in transplanted rat hormone-secreting pituitary tumors MtTW15 and 7315a and in the host pituitary gland. The elevated serum-hormone concentrations produced by 7315a tumor decreased the size of the host's pituitary gland, its hormone content, and G6P-DH, LDH, PK, and ICDH, but produced no changes in MDH, acid phosphatase, cathepsin-D, and LYSAR enzyme activities (mU/mg tissue). LDH and PK activities were greater in unit weight of pituitary tumors than in pituitary glands. Although more G6P-DH was found in MtTW15 tumor than in normal pituitary tissue, less of the enzyme was detected in 7315a pituitary tumor. It is concluded that elevated serum pituitary hormones selectively decrease hormone production and the activity of some enzymes in the pituitary gland, presumably through a feedback mechanism.
Mol Cell Endocrinol 1979 Mar
PMID:Some biochemical characteristics of hormone-secreting pituitary tumors and of the host's anterior pituitary gland. 3 16

The mechanism of the inhibitory effect of local anesthetics on hormone secretion was studied in the GH4C1 line of rat pituitary tumor-derived cells. Lidocaine between 0.1 and 5 mM exerted significant dose-dependent inhibition on the increment in cytosol Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion induced by 30 mM K+. For both effects the IC50 was 0.25 mM and maximal inhibition occurred at 5 mM. A normal response returned within 20 min after removal of lidocaine from the incubation medium. 1 microM tetrodotoxin had no effect on the 30 mM K+ induced [Ca2+]i transient or PRL secretion, indicating that Na+ channels are not involved in the inhibitory effect of lidocaine. Lidocaine similarly inhibited the [Ca2+]i increment and PRL secretion induced by 30% medium hyposmolarity and 1 microM Bay K 8644. Lidocaine was much less effective in inhibiting secretion induced by 1 microM phorbol 12-myristate 13-acetate (TPA) or 5 microM forskolin. 5 mM procaine produced effects similar to those of lidocaine. Our data suggest that in GH4C1 cells local anesthetics depress secretagogue-induced PRL secretion primarily by blocking Ca2+ influx, probably through L-type Ca2+ channels.
Mol Cell Endocrinol 1992 Sep
PMID:Lidocaine inhibits prolactin secretion in GH4C1 cells by blocking calcium influx. 128 Feb 32

alpha-Adrenergic receptors are present on the plasma membrane of normal anterior pituitary cells and alpha-adrenergic agonists may play a role in the secretion of corticotropin (ACTH) and thyrotropin (TSH). However, alpha-adrenergic involvement in prolactin (PRL) secretion is uncertain. We have therefore examined this question in the PRL-secreting clonal rat pituitary tumor-derived GH4C1 cells. Norepinephrine (NE), an alpha-adrenergic agonist, had no effect on basal PRL secretion but abolished thyrotropin-releasing hormone (TRH)-induced PRL secretion in a dose-dependent manner (EC50 100 nM). NE also significantly suppressed the TRH-stimulated rise in [Ca2+]i. Phentolamine (PA), a non-selective alpha-adrenergic antagonist, reversed the inhibitory effect of NE on both the TRH-stimulated PRL secretion and [Ca2+]i rise. NE did not inhibit the rise in PRL secretion or [Ca2+]i induced by depolarizing 30 mM K+, 30% hyposmolarity or BAY K-8644, a specific L-type Ca2+ channel agonist. The inhibitory effect of NE on TRH-induced PRL and [Ca2+]i changes was also present when Ca2+ influx was prevented by removing medium Ca2+ or by blocking L-type Ca2+ channels with 2 microM nifedipine. The TRH-stimulated first-phase rise in [Ca2+]i in GH4C1 cells is believed to result primarily from release of sequestered Ca2+ from an intracellular pool through the activation of inositol 1,4,5-trisphosphate (IP3) and this [Ca2+]i spike stimulates PRL secretion. Our data thus suggest that GH4C1 cells have alpha-adrenergic receptors and that alpha-adrenergic agonists either suppress IP3 generation or block IP3 release of sequestered intracellular Ca2+.
Mol Cell Endocrinol 1992 Sep
PMID:Alpha-adrenergic inhibition of thyrotropin-releasing hormone-induced prolactin secretion in GH4C1 cells is associated with a depressed rise in intracellular Ca2+. 128 Feb 33

The 7315c cell, derived from a rat anterior pituitary tumor, expresses an angiotensin II (AII) receptor. [3H]AII binds to 7315c membranes specifically and saturably (Kd = 2.1 +/- 0.6 x 10(-6) M, Bmax = 282 +/- 33 fmol/mg of protein). GTP diminished the affinity of the membranes for [3H]AII (Kd = 4.1 +/- 0.4 x 10(-9) M, Bmax = 210 +/- 26 fmol/mg of protein). [3H]AII binding was displaced by AII (Ki = 1.3 +/- 0.6 x 10(-9) M), angiotensin III (AIII) (Ki = 0.9 +/- 0.4 x 10(-9) M), and the nonpeptide AII antagonist DuP753 (Ki = 1.4 +/- 0.6 x 10(-8) M). In contrast, a second nonpeptide AII ligand, PD123177, did not compete for [3H]AII binding sites. In intact cells, AII and AIII stimulated inositol trisphosphate (IP3) production (EC50 = 1.1 +/- 0.6 x 10(-8) M and 1.1 +/- 0.5 x 10(-8) M, respectively); this response to AII was antagonized by DuP753 (Ki = 1.7 +/- 0.3 x 10(-7) M). Pertussis toxin treatment failed to affect the ability of AII to stimulate IP3 production. In a crude membrane preparation, GTP was required for maximal AII-induced IP3 stimulation; guanosine thio-diphosphate abolished the agonist-GTP stimulation of IP3 production, in a concentration-dependent fashion. AII and AIII also inhibited adenylyl cyclase (EC50 = 2.9 +/- 1.1 x 10(-8) M and 6.0 +/- 1.0 x 10(-8) M, respectively). DuP753 antagonized the inhibition by AII of adenylyl cyclase (Ki = 2.8 +/- 0.4 x 10(-8) M). PD123177 failed to antagonize AII-induced cyclase inhibition. Pertussis toxin treatment abolished the AII and AIII inhibition of adenylyl cyclase. GTP was required for AII-induced inhibition of adenylyl cyclase. These data suggest that, in 7315c cells, a single subtype of AII receptor, identified by DuP753, is capable of regulating two different guanine nucleotide-binding protein (G protein) signalling pathways; one G protein, which is insensitive to pertussis toxin, stimulates IP3 production and the other G protein, which is sensitive to pertussis toxin, inhibits adenylyl cyclase.
Mol Pharmacol 1992 Jan
PMID:Angiotensin II receptor recognized by DuP753 regulates two distinct guanine nucleotide-binding protein signaling pathways. 131 Jan 39

The hallmark of ACTH oversecretion in Cushing's disease is its partial resistance to the normal suppressive effect of glucocorticoids. Because ACTH secretion by the pituitary tumor is not normally restrained ACTH is overproduced with subsequent chronic hypercortisolism. Since peripheral tissues have retained their normal sensitivity to the action of cortisol they appropriately develop the features of Cushing's disease. The question of whether a collection of corticotroph cells, eventually arranged in an adenomatous-like fashion, is a primary pituitary event or is corticotropin-releasing factor driven has had no response so far. Clonal composition of such lesions has been determined by X chromosome inactivation using DNA probes which detect multiallelic polymorphism in females. A monoclonal pattern is found in all macroadenomas. ACTH is co-secreted with other peptide fragments derived from their common polypeptide precursor, proopiomelanocortin (POMC). As a rule POMC processing in pituitary tumors is qualitatively unaltered: plasma values of the N-terminal fragment, the joining peptide, the beta- and gamma-lipotropins, and beta-endorphin all are valid alternate markers of the tumor activity. Tumor POMC peptides including ACTH and its phosphorylated form usually show no peculiar or unexpected molecular forms in contrast with what is often found when POMC expression occurs in a non-pituitary tumor.
J Steroid Biochem Mol Biol 1992 Oct
PMID:Unrestrained production of proopiomelanocortin (POMC) and its peptide fragments by pituitary corticotroph adenomas in Cushing's disease. 132 71

In order to elucidate the complex mechanism(s) of action of steroid hormones, thyroid hormone and retinoic acid in pituitary mammotrophs, a clonal cell line (G3) was isolated from the rat pituitary tumor MtT/F84. G3 cells were found to secrete prolactin constitutively and to contain receptors for estrogen, glucocorticoid, progesterone and thyroid hormone. Stimulation of G3 cells with thyroid hormone resulted in a modest but significant increase in estrogen and progesterone receptor levels, however, retinoic acid treatment had no effect. Simultaneous addition of thyroid hormone and estrogen showed an additive effect on progesterone receptor levels in G3 cells. Thyroid hormone as well as estrogen enhanced the growth of G3 cells. Interestingly, retinoic acid was also found to enhance their growth but its enhancement was less potent than thyroid hormone and estrogen. Low concentrations of estradiol and thyroid hormone showed additive effects, but G3 cells stimulated with high concentrations of thyroid hormone failed to elicit an additive effect with estrogen, suggesting the presence of a common pathway in the growth-stimulatory actions of these hormones. In addition, exposure of G3 cells to retinoic acid completely abolished the effects of estrogen or thyroid hormone in terms of cell growth. These results suggest that there are complex interactions in the signalling pathways for estrogen, thyroid hormone and retinoic acid action in G3 cells.
J Steroid Biochem Mol Biol 1992 Oct
PMID:Effects of retinoic acid on estrogen- and thyroid hormone-induced growth in a newly established rat pituitary tumor cell line. 139 Feb 78

Previous observations that extracellular calcium (Ca2+) enhanced PRL mRNA levels posttranscriptionally in GH3 rat pituitary tumor cells were made using double-stranded transcription probes. The effects of Ca2+ and the Ca2+ ionophore, ionomycin, on PRL gene expression in GH3 and 235-1 cells were investigated using site- and strand-specific probes. Treatment of GH3 and 235-1 cells with 0.5 mM Ca2+ in serum-free medium specifically increased PRL mRNA levels by severalfold. In 235-1 but not GH3 cells PRL gene transcription was comparably induced by Ca2+. Use of single-stranded 5' and 3' probes revealed no antisense transcription, nor any Ca2+ effect on transcriptional elongation. Treatment with Ca2+ plus ionomycin inhibited PRL mRNA levels and gene transcription in both cell lines. Although their PRL gene transcription rates are similar, several basic differences were noted between the cell lines. The 235-1 cells exhibit a different profile of nuclear PRL pre-RNAs than GH3 cells. Also, mRNA levels for a Ca(2+)-regulated gene (GRP78) did not change in Ca(2+)-treated GH3 cells but decreased in Ca(2+)-treated 235-1 cells. Ionomycin treatment increased GRP78 mRNA levels in both cell lines. Thus, addition of extracellular Ca2+ appears to affect [Ca2+]i in 235-1 but not GH3 cells, while ionomycin affects [Ca2+]i in both cell lines. These data suggest that changing [Ca2+]i modulates PRL gene transcription. The comparative data suggest that posttranscriptional PRL regulation is Ca(2+)-regulated in GH3 cells, but is constitutive in 235-1 cells.
Mol Endocrinol 1992 Aug
PMID:Effects of calcium and calcium ionophores on prolactin gene expression in GH3 and 235-1 rat pituitary tumor cells. 140 4

Relaxin is a polypeptide hormone involved in remodeling of the birth canal during parturition. It is synthesized as a preprohormone precursor, which undergoes specific processing to form the mature two-chain disulfide-linked active species that is secreted by the cell. A major part of this processing requires endoproteolytic cleavage at specific pairs of basic amino acid residues, an event necessary for the maturation of a variety of important biologically active proteins, such as insulin and nerve growth factor. Human type 2 preprorelaxin was coexpressed in human kidney 293 cells with the candidate prohormone convertase-processing enzymes mPC1 or mPC2, both cloned from the mouse pituitary tumor AtT-20 cell line, or with the yeast kex2 alpha-mating factor-converting enzyme from Saccharomyces cerevisiae. Prorelaxin expressed alone in 293 cells was secreted into the culture medium unprocessed. Transient coexpression with mPC1 or kex2, but not with mPC2, resulted in the secretion of a low mol wt species with an electrophoretic mobility very similar, if not identical, to that of authentic mature relaxin purified from human placenta. This species was precipitable by monoclonal antibodies specific for relaxin and had a retention time on reverse phase HPLC comparable to that of relaxin. Its analysis by both electrospray and fast atom bombardment mass spectrometry generated mass data that were consistent only with mature relaxin. The basic residues required for mPC1-dependent cleavage of prorelaxin are defined by site-directed mutagenesis.
Mol Endocrinol 1992 Sep
PMID:Prohormone convertase-1 will process prorelaxin, a member of the insulin family of hormones. 143 88

We have shown that growth of F4Z2 cells and F4Z2 tumors was stimulated by estradiol, that of MtTF4 and F4P tumors was inhibited and that of F4P cells remained insensitive. In the present work we explore the possible role of transforming growth factor-beta (TGF-beta) as a mediator of estradiol action in these pituitary tumors and cell lines. In vivo, estradiol treatment increased the concentration of TGF-beta 1 mRNAs in tumors whose growth was inhibited by estradiol (MtTF4 and F4P) but not in tumors whose growth was stimulated (F4Z2). F4Z2 and F4P cell lines also contained TGF-beta 1 transcripts. These cells and tumors differed by two points: the level of TGF-beta 1 transcript was higher in F4Z2 than in F4P cells while the opposite situation was observed in vivo and the concentration of TGF-beta 1 mRNA in cultured cells was insensitive to estradiol (1 or 100 x 10(-9) M). Moreover, the secretion of TGF-beta like activity assayed by two different methods was estradiol insensitive and the growth of both cell lines was dose-dependently inhibited by TGF-beta 1 (ED50:2 x 10(-11) M). Since estradiol increases TGF-beta 1 mRNA in the tumors MtTF4 and F4P whose growth is inhibited by estradiol and that TGF-beta 1 inhibits the proliferation of F4P cells it is proposed as a working hypothesis that TGF-beta 1 is one of the mediators of the inhibitory effect of estradiol in pituitary tumors. No data favor the hypothesis that estradiol stimulates pituitary tumor proliferation by decreasing TGF-beta production.
J Steroid Biochem Mol Biol 1992 Feb
PMID:Possible involvement of transforming growth factor-beta in the inhibition of rat pituitary tumor growth by estradiol. 154 79

Previously, we have studied thyroid hormone-dependent growth of GH1 rat pituitary tumor cells in iron-restricted serum-free defined medium (Sirbasku, D.A., et al. (1991) Biochemistry 30, 295-304, 7466-7477). Proliferation was promoted by triiodothyronine (T3) and any of seven forms of horse serum-derived apotransferrin (apoTf). In this report, we have asked if apoTfs from other species also acted as thyromedins and if other metal ion chelators served this role. To address these issues, three thyromedins were isolated from human serum and identified as apoTf. Fe3+ depletion, and assay in low-Fe medium, gave ED50s of 1.4-1.7 nM. Fe3+ saturation abolished their activities in high-Fe medium. To ask if apoTf was the major thyromedin in human serum, hormone-depleted preparations were iron saturated and shown to no longer support T3-dependent GH1 cell growth. Next, commercially prepared human, rat, horse, dog, rabbit, guinea pig and mouse apoTfs were shown to be as active under iron-restricted conditions as those isolated from human serum. Bovine apoTf and colostrum lactoferrin were greater than 100-fold less active; human milk apo-lactoferrin and apo-ovotransferrins were inactive. Transferrins which displayed thyromedin activity blocked the binding of 125I-rat 2Fe.Tf to GH1 cell receptors while those without thyromedin activity were ineffective. Finally, the metal ion chelators EDTA, citrate and deferoxamine did not show thyromedin activity indicating that apoTfs uniquely were able to promote T3-dependent cell growth in defined culture.
Mol Cell Endocrinol 1992 Feb
PMID:Apotransferrins from several species promote thyroid hormone-dependent rat pituitary tumor cell growth in iron-restricted serum-free defined culture. 154 14


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