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

The ability of adrenocortical cells to degrade ACTH1--39 and [125I]ACTH has been assessed under various conditions. Under conditions leading to increased hormone degradation there was an elevation of both the ED50 and the value of the Hill coefficient derived from concentration-effect curves for ACTH-stimulated steroidogenesis. Such degradative mechanisms offer a simple explanation for tha apparent positive cooperativity proposed by others for ACTH-receptor-adenylate cyclase interactions.
Mol Cell Endocrinol 1977 Jan
PMID:Apparent positive cooperativity of ACTH action on adrenocortical cells: the effect of hormone degradation. 18 4

Cells were dissociated from normal rat pituitaries by a combination of mechanical agitation and enzymatic action, seeded into culture flasks and grown in monolayer culture. When such cells were exposed to an extract of the hypothalamic stalk-median eminence area (HSME) a dose-dependent secretion of ACTH was observed. A 2-h exposure to Ca-free media significantly reduced the HSME-stimulated release of ACTH but the measured levels were still greater than the unstimulated controls. When the 45Ca2+ uptake into the cultured cells was measured both control and HSME-stimulated cells yielded identical results (60-80 nmol Ca/mg cell protein). Upon removal of the calcium associated with the surface coat it was found that HSME actually decreased the cellular uptake of calcium. Since variations in uptake can result from changes in influx or efflux as well as from variations in pool size or turnover times of calcium exchange with intracellular compartments, a series of isotope washout experiments were performed. Neither HSME nor theophyline affected the rate constant of calcium efflux from what is believed to be the cytosol pool to the extracellular media. Both agents, however, prompted a shift of intracellular calcium into a more tightly bound compartment. The data suggest that the calcium required for pituitary hormone secretion is derived primarily from an intracellular rather than extracellular origin. It may be that, via the action of cyclic AMP, such calcium can be mobilized from intracellular stores and shifted to a more tightly bound compartment where it can participate in the intracellular processes associated with secretion.
Mol Cell Endocrinol 1977 Feb
PMID:Involvement of intracellular calcium in hormone secretion from pituitary cells. 19 67

Biochemical and ultrastructural studies indicate that the atrophy of adrenal cortex in hypoyhysectomized rats involves the following changes: (1) One to two days after hypophysectomy, there is loss of "template activity" resulting from cumulative DNA-damage and heterochromatinization. In vivo ACTH-administration led to recuperation of these cells, indicating damage during hypophysectomized state to be reversible. (2) If the duration of hypophysectomy is prolonged, some of the cells become irreversibly damaged and can no longer recuperate after in vivo ACTH administration. (3) The period of most rapid cell death is from the third to seventh day after hypophysectomy. The cause of cell death is probably due to membrane damage in the absence of protein synthesis, leading to lysis of the cells. Lysozomes and macrophages are apparently not involved.
Mol Cell Biochem 1977 Apr 12
PMID:Studies on the adrenal cortex of hypophysectomized rats: a model for abnormal cellular atrophy and death. 19

A somatic cell genetic approach was used to study the role of cyclic nucleotides in adrenal steroidogenesis. 8-Bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated steroidogenesis (K'd=0.1 mM) in cultured mouse adrenocortical tumor cells (Clone Y1). In addition, 8BrcAMP inhibited Y1 cell growth and caused Y1 cell monolayers to assume a rounded morphology. As a consequence, 8BrcAMP (at concentrations greater than or equal to 0.4 mM) reduced the relative plating efficiency of Y1 cells to less than 10(-5). Y1 cells were mutagenized with ethyl methanesulfonate (300 microgram/ml) and grown in the presence of 0.4 mM 8BrcAMP. A surviving colony (8BrcAMPr-1) was shown to be resistant to growth inhibition (relative plating efficiency at 1.0 mM 8BrcAMP=50 percent)) and to morphological changes induced by 8BrcAMP. 8BrcAMPr-1 cells had diminished steroidogenic responses to cyclic nucleotides and to ACTH (less than or equal to 33 percent of maximum). In 8BrcAMP(R)-1 cells, adenylate cyclase activity remained responsive to ACTH, and cyclic AMP phosphodiesterase activity was not increased. These data suggest that 8BrcAMPr-1 cells are defective at a point common to cyclic AMP action on growth, morphology and steroidogenesis. The associated decrease in responsiveness of the steroidogenic pathway to ACTH suggests that ACTH-regulated steroidogenesis is via a cyclic nucleotide-mediated mechanism.
Mol Cell Endocrinol 1977 Aug
PMID:Isolation of mutant adrenocortical tumor cells resistant to cyclic nucleotides. 20 May 6

Calcium salts were found to replace ACTH in inducing steroidogenesis in isolated adrenocortical cells from rats. This Ca-specific stimulation occurred when the cation was presented to the cells in the presence of phosphate and carbonate as a counter-ions under conditions which favoured the formation of colloidal calcium. Colloid generation and stabilization was facilitated by the use of calcium buffers and gelatin. Stable soluble or sparingly soluble calcium complexes were inactive. The preparation of cells and metastable calcium solutions is described in detail. The Ca trigger was sensitive to Ca deprivation or inhibitors of Ca transport and could be replced by Sr. The relative role of Ca and cyclic AMP as second messengers is discussed.
Mol Cell Endocrinol 1978 Jan
PMID:Steroidogenesis in isolated adrenal cells: excitation by calcium. 20

Isolated pituitary cells prepared from adrenalectomized rats secrete ACTH in response to CRF, and this response is inhibited by corticosterone. Both the stimulation of release by CRF and the inhibition of release by corticosterone are antagonized by cordycepin (3'-deoxyadenosine). Inhibition of CRF-stimulated secretion by cordycepin is apparently not related to inhibition of RNA synthesis, since high doses of actinomycin D do not affect ACTH secretion. More likely, cordycepin's inhibition of secretion stems from its inhibition of adenylate cyclase activity. Inhibition of corticosterone action by cordycepin is qualitatively similar to that previously reported actinomycin D. This effect of both drugs is probably due to inhibition of RNA synthesis. Significantly, a low dose of cordycepin has a greater inhibitory effect on corticosterone action than on total cellular RNA synthesis. Cordycepin is reported to preferentially inhibit messenger RNA synthesis, and low dose preferentially inhibits appearance of cytoplasmic RNA in pituitary cells. These data suggest that corticosterone-induced RNA is a cytoplasmic (messenger) RNA.
Mol Cell Endocrinol 1978 Jan
PMID:Effect of cordycepin on CRF stimulation and steroid inhibition of ACTH secretion by rat pituitary cells. 20 1

Y-1 adrenal tumor cells were incubated with aminoglutethimide with and without ACTH. Greater production of pregnenolone from endogenous cholesterol was observed (after washing to remove aminoglutethimide) in mitochondria from cells incubated with aminoglutethimide and ACTH than in those from cells incubated with aminoglutethimide alone. This response was inhibited by cycloheximide and puromycin but not by chloramphenicol or actinomycin D. ACTH increased the incorporation of [3H]tyrosine into protein associated with mitochondria but not into total cell protein or protein of postmitochondrial supernatant. This response did not require aminoglutethemide block and was inhibited by cycloheximide and puromycin but not by chloramphenicol or actinomycin D. Dibutyryl cyclic AMP produced both of these responses (increased production of pregnenolone and synthesis of protein associated with mitochondria). The concentration of cycloheximide required to cause 50% inhibition of the responses to ACTH and dibutyryl cyclic AMP was approximately the same for steroidogenesis by whole cells, for production of pregnenolone by isolated mitochondria, for incorporation of [3H]tyrosine into Y-1 cell protein and for the increase in synthesis of protein associated with mitochondria produced by ACTH (0.08--0.2 microgram/ml). Disc gel electrophoresis revealed that the increased incorporation of [3H]tyrosine involved two proteins corresponding to molecular weight of approximately 27,000 and 13,000 respectively. These observations suggest that ACTH promotes synthesis of protein(s) by cytoplasmic ribosomes on stable messenger RNA, that the protein(s) becomes associated with mitochondria and that the protein(s) includes one or more which are associated with the increase in production of pregnenolone produced in mitochondria by the addition of ACTH to adrenal cells.
Mol Cell Endocrinol 1978 Nov
PMID:On the role of protein synthesis in the response of adrenal tumor cells to ACTH. 21 75

Specific radioimmunoassays (RIAs) for ACTH, beta-endorphin, alpha-MSH and beta-MSH were used to identify the immunoreactive components released during incubation of rat anterior pituitary cells in primary culture. Such measurements were performed after separation of the incubation media by chromatography on Sephadex G-50 or G-75. The ACTH-RIA measured approximately equal amounts of 13 and 4.5K ACTH while equal proportions of components migrating at the position of beta-LPH and beta-endorphin were measured in the beta-endorphin RIA system. Immunoreactive components migrating at the position of gamma-LPH and alpha-MSH were measured in the beta-MSH and alpha-MSH RIA systems, resp. 3 purified corticotropin-releasing fractions (CRF) prepared from porcine hypothalami and increasing concentrations of N6,O2'-dibutyryl cyclic AMP and theophylline led to parallel release of ACTH, beta-endorphin, beta-MSH and alpha-MSH immunoreactivities while preincubation with dexamethasone led to a 30-60% inhibition of the release of all peptides. The present data show that the release of ACTH, beta-LPH, beta-endorphin, gamma-LPH and alpha-MSH-like immunoeactivities occurs in parallel in anterior pituitary cells in culture both under basal and acute stimulatory or inhibitory conditions of release.
Mol Cell Endocrinol 1979 Nov
PMID:Parallel release of ACTH, beta-endorphin, alpha-MSH and beta-MSH-like immunoreactivities in rat anterior pituitary cells in culture. 22 47

Protein biosynthesis in neurointermediate lobes of mouse pituitaries was investigated using pulse and pulse-chase techniques with [3H]lysine. Electrophoretic analysis of lobe homogenates on acid-urea gels resolved 11 labeled products. One was a large protein which was rapidly synthesized during pulse-incubations and disappeared during chase incubations. Three of the products increased during chase incubations, suggesting a precursor-product mode of biosynthesis for these chasde peptides. One of these three products co-migrated with synthetic alpha-MSH and also corresponds to the major peak of mouse neurointermediate lobe MSH bioactivity and immunoactivity on electrophoretograms. Another case of these peptides has electrophoretic properties similar to those of ACTH.
Mol Cell Endocrinol 1979 Feb
PMID:Biosynthesis of MSH and related peptides in the pars intermedia of the mouse: a pulse-chase analysis. 44 80

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


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