Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The primary function of the corpus luteum is secretion of the hormone progesterone, which is required for maintenance of normal pregnancy in mammals. The corpus luteum develops from residual follicular granulosal and thecal cells after ovulation. Luteinizing hormone (LH) from the anterior pituitary is important for normal development and function of the corpus luteum in most mammals, although growth hormone, prolactin, and estradiol also play a role in several species. The mature corpus luteum is composed of at least two steroidogenic cell types based on morphological and biochemical criteria and on the follicular source of origin. Small luteal cells appear to be of thecal cell origin and respond to LH with increased secretion of progesterone. LH directly stimulates the secretion of progesterone from small luteal cells via activation of the protein kinase A second messenger pathway. Large luteal cells are of granulosal cell origin and contain receptors for PGF(2alpha) and appear to mediate the luteolytic actions of this hormone. If pregnancy does not occur, the corpus luteum must regress to allow follicular growth and ovulation and the reproductive cycle begins again. Luteal regression is initiated by PGF(2alpha) of uterine origin in most subprimate species. The role played by PGF(2alpha) in primates remains controversial. In primates, if PGF(2alpha) plays a role in luteolysis, it appears to be of ovarian origin. The antisteroidogenic effects of PGF(2alpha) appear to be mediated by the protein kinase C second messenger pathway, whereas loss of luteal cells appears to follow an influx of calcium, activation of endonucleases, and an apoptotic form of cell death. If the female becomes pregnant, continued secretion of progesterone from the corpus luteum is required to provide an appropriate uterine environment for maintenance of pregnancy. The mechanisms whereby the pregnant uterus signals the corpus luteum that a conceptus is present varies from secretion of a chorionic gonadotropin (primates and equids), to secretion of an antiluteolytic factor (domestic ruminants), and to a neuroendocrine reflex arc that modifies the secretory patterns of hormones from the anterior pituitary (most rodents).
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PMID:Mechanisms controlling the function and life span of the corpus luteum. 1061 64

1. In rat pituitary tumour cells (GC cells), spontaneous oscillations of the intracellular concentration of Ca2+ ([Ca2+]i) induce growth hormone (GH) secretion that is inhibited by octreotide, a somatostatin (SRIF) agonist which binds to SRIF subtype (sst) receptor 2. The effects of its functional activation on the control of [Ca2+]i were investigated using fluorimetric measurements of [Ca2+]i. 2. SRIF decreases the basal [Ca2+]i and the [Ca2+]i rise in response to forskolin (FSK) through the inhibition of L-type voltage-dependent Ca2+ channels. 3. Pretreatment with octreotide or with L-Tyr8++ Cyanamid 154806, a sst2 receptor antagonist, abolishes the SRIF-induced inhibition of [Ca2+]i. Octreotide is known to operate through agonist-induced desensitization, while the antagonist operates through receptor blockade. 4. sst1 and sst2 receptor-immunoreactivities (-IRs) are localized to cell membranes. sst2, but not sst1 receptor-IR, internalizes after cell exposure to octreotide. 5. SRIF-induced inhibition of basal [Ca2+]i or FSK-induced Ca2+ entry is blocked by pertussis toxin (PTX). 6. FSK-induced cyclic AMP accumulation is only partially decreased by SRIF or octreotide, indicating that sst2 receptors are coupled to intracellular pathways other than adenylyl cyclase (AC) inhibition. 7. In the presence of H-89, an inhibitor of cyclic AMP-dependent protein kinase (PKA), SRIF-induced inhibition of basal [Ca2+]i is still present, although reduced in amplitude. 8. SRIF inhibits [Ca2+]i by activating sst2 receptors. Inhibition of AC activity is only partly responsible for this effect, and other transduction pathways may be involved.
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PMID:Somatostatin-induced control of cytosolic free calcium in pituitary tumour cells. 1071 45

The electrophysiological properties of anterior pituitary somatotropes integrally involve the function of voltage-gated K+ currents. In this study, we have used GH4C1 cell lines to investigate the effect of human GHRH on voltage-gated K+ currents. Because of a clear 'rundown' of the K+ current with classic whole cell recording (WCR) without ATP in pipette solution, nystatin-perforated WCR was the major recording configuration used. Using a low Ca2+ (0.5 mM) bath solution containing Co2+ (1 mM) and TTX (1 microM), GH4 cells predominantly exhibited an outward delayed rectifier K+ current (IK). Local application of growth hormone releasing hormone (GHRH) (100 nM) reversibly reduced the amplitude of the K+ currents (to 83% of control). There was no effect of GHRH on the activation curve of the K+ current and no difference observed using 2.5 mM Ca2+ or low Ca2+ (0.5 mM Ca2++1 mM Co2+) bath solutions. Under the condition of low Ca2+ bath solution, the application of apamin (1 microM) or charybdotoxin (1 microM), two specific blockers of the Ca2+-activated K+ current, did not alter the K+ current or the response to GHRH. This reduction in the K+ current by GHRH was also observed with classic WCR with a pipette solution containing ATP (2 mM). The GHRH-induced reduction in the K+ current was completely abolished by the presence of GDP-beta-s (500 microM) in the pipette solution or by addition of PKC inhibitors, calphostin C (100 nM) and chelerythrine (1 microM), in bath solution. Inhibitor for cAMP-PKA system (Rp-cAMP and H89) did not affect the K+ current response to GHRH. These results suggest that GHRH reduces the voltage-gated K+ current in GH4C1 cells, a response that is mediated by G-proteins and PKC system but not by cAMP-PKA system. The reduction in the K+ current may partially contribute to the GHRH-stimulated growth hormone (GH) secretion.
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PMID:Growth hormone-releasing hormone decreases voltage-gated potassium currents in GH4C1 cells. 1071 10

We have examined the role of CrkII in the cellular response to both human growth hormone (hGH) and human insulin-like growth factor-1 (hIGF-1). We have demonstrated that overexpression of the adaptor molecule enhances both basal phosphatidylinositol 3-kinase (PI 3-kinase) activity and also dramatically enhances the ability of both hormones to stimulate PI 3-kinase activity in the cell. Many of the effects of CrkII overexpression on hGH- and hIGF-1-stimulated cellular function can then be attributed to CrkII enhancement of PI 3-kinase stimulation by these hormones. Thus, CrkII-enhanced PI 3-kinase activity is used to enhance actin filament reorganization in response to both hGH and hIGF-1, to enhance stress activated protein kinase (SAPK) activity in response to hGH, and to diminish STAT5-mediated transcription in response to hGH. It is apparent, however, that CrkII also regulates cellular function independent of its ability to stimulate PI 3-kinase activity. This is evidenced by the ability of CrkII, in a PI 3-kinase-independent manner, to diminish the activation of p44/42 mitogen-activated protein kinase in response to both hGH and hIGF-1 and to inhibit the activation of SAPK by hIGF-1. Therefore, despite the common use of CrkII to activate PI 3-kinase, CrkII also allows hGH or hIGF-1 to selectively switch the activation of SAPK. Thus, common utilization of CrkII by hGH and hIGF-1 allows the execution of common cellular effects of these hormones, concomitant with the retention of hormonal specificity.
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PMID:CrkII participation in the cellular effects of growth hormone and insulin-like growth factor-1. Phosphatidylinositol-3 kinase dependent and independent effects. 1074 58

Secretin, glucagon, gastric inhibitory polypeptide (GIP), and parathyroid hormone (PTH) belong, together with vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase (AC)-activating polypeptide, to a family of peptides (the VIP-secretin-glucagon family), which also includes growth hormone-releasing hormone and exendins. All the members of this peptide family possess a remarkable amino-acid sequence homology, and bind to G-protein-coupled receptors, whose signaling mechanism primarily involves AC/protein kinase A and phospholipase C/protein kinase C cascades. VIP and pituitary AC-activating polypeptide play a role in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and in this review we survey findings that also other members of the VIP-secretin-glucagon family may have the same function. Secretin and secretin receptors are expressed in the hypothalamus and pituitary gland, and secretin inhibits adrenocorticotropic hormone (ACTH) release. No evidence is available for the presence of secretin receptors in adrenal glands, but secretin selectively depresses the glucocorticoid response to ACTH of dispersed zona fasciculata-reticularis (ZF/R) cells. Glucagon and glucagon-like peptide-1 are contained in the hypothalamus, and all the components of the HPA axis are provided with glucagon and glucagons-like-1 receptors. These peptides exert a short-term inhibitory effect on stress-induced pituitary ACTH release and depress the ZF/R cell response to ACTH by inhibiting the AC/protein kinase A cascade; they also stimulate hypothalamic arginine-vasopressin release. GIP receptors are present in the ZF/R of the normal adrenals, and are particularly abundant in some types of adrenocortical adenomas and hyperplasias. GIP, through the activation of the AC/protein kinase A cascade, evokes a sizeable glucocorticoid secretagogue effect, leading to the identification of a food/GIP-dependent Cushing's syndrome. PTH and PTH-related protein are expressed in the hypothalamus and pituitary gland, and PTH and PTH-related protein receptors in all the components of the HPA axis. Both peptides enhance ACTH and arginine-vasopressin release, as well as stimulate aldosterone and glucocorticoid secretion of dispersed zona glomerulosa and ZF/R cells, respectively. The involvement of growth hormone-releasing hormone and exendins in the functional regulation of the HPA axis has not yet been extensively investigated.
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PMID:Secretin, glucagon, gastric inhibitory polypeptide, parathyroid hormone, and related peptides in the regulation of the hypothalamus- pituitary-adrenal axis. 1076 61

Influx of Ca2+ via Ca2+ channels is the major step triggering exocytosis of pituitary somatotropes to release growth hormone (GH). Voltage-gated Ca2+ and K+ channels, the primary determinants of the influx of Ca2+, are regulated by GH-releasing hormone (GHRH) through G-protein-coupled intracellular signalling systems. Using whole-cell patch-clamp techniques, the changes of the Ca2+ and K+ currents in primary cultured ovine and human somatotropes were recorded. Growth hormone-releasing hormone (10 nmol/L) increased both L- and T-type voltage-gated Ca2+ currents. Inhibition of the cAMP/protein kinase A (PKA) pathway by either Rp-cAMP or H89 blocked this increase in both L- and T-type Ca2+ currents. Growth hormone-releasing hormone also decreased voltage-gated transient (IA) and delayed rectified (IK) K+ currents. Protein kinase C (PKC) inhibitors, such as calphostin C, chelerythrine or downregulation of PKC, blocked the effect of GHRH on K+ currents, whereas an acute activation of PKC by phorbol 12, 13-dibutyrate (1 micromol/L) mimicked the effect of GHRH. Intracellular dialysis of a specific PKC inhibitor (PKC19-36) also prevented the reduction in K+ currents by GHRH. It is therefore concluded that GHRH increases voltage-gated Ca2+ currents via cAMP/PKA, but decreases voltage-gated K+ currents via the PKC signalling system. The GHRH-induced alteration of Ca2+ and K+ currents augments the influx of Ca2+, leading to an increase in [Ca2+]i and the GH secretion.
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PMID:Diverse intracellular signalling systems used by growth hormone-releasing hormone in regulating voltage-gated Ca2+ or K channels in pituitary somatotropes. 1094 60

Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel member of the secretin-glucagon peptide family. In mammals, this peptide has been located in a wide range of tissues and is involved in a variety of biological functions. In lower vertebrates, especially fish, increasing evidence suggests that PACAP may function as a hypophysiotropic factor regulating pituitary hormone secretion. PACAP has been identified in the brain-pituitary axis of representative fish species. The molecular structure of fish PACAP is highly homologous to mammalian PACAP. The prepro-PACAP in fish, however, is distinct from that of mammals as it also contains the sequence of fish GHRH. In teleosts, the anterior pituitary is under direct innervation of the hypothalamus and PACAP nerve fibers have been identified in the pars distalis. Using the goldfish as a fish model, mRNA transcripts of PACAP receptors, namely the PAC1 and VPACI receptors, have been identified in the pituitary as well as in various brain areas. Consistent with the pituitary expression of PACAP receptors, PACAP analogs are effective in stimulating growth hormone (GH) and gonadotropin (GTH)-II secretion in the goldfish both in vivo and in vitro. The GH-releasing action of PACAP is mediated via pituitary PAC1 receptors coupled to the adenylate cyclase-cAMP-protein kinase A and phospholipase C-IP3-protein kinase C pathways. Subsequent stimulation of Ca2+ entry through voltage-sensitive Ca2+ channels followed by activation of Ca2+-calmodulin protein kinase II is likely the downstream mechanism mediating PACAP-stimulated GH release in goldfish. Although the PACAP receptor subtype(s) and the associated post-receptor signaling events responsible for PACAP-stimulated GTH-II release have not been characterized in goldfish, these findings support the hypothesis that PACAP is produced in the hypothalamus and delivered to the anterior pituitary to regulate GH and GTH-II release in fish.
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PMID:Pituitary adenylate cyclase activating polypeptide as a novel hypophysiotropic factor in fish. 1094 84

The growth hormone-releasing hormone (GHRH) gene produces a precursor molecule that contains GHRH and a carboxyl-terminal peptide that we have named GHRH-related peptide (GHRH-RP). This peptide, like GHRH, stimulates the expression of stem cell factor (SCF), an important reproductive and hematopoietic cytokine, in vitro and in vivo. In the present study, using primary cultures of rat Sertoli cells, we compared the time course of action and the level of SCF stimulation seen following treatment with GHRH-RP and GHRH. Additionally, we investigated the activity of a truncated peptide, p75-92NH2, whose sequence is contained within GHRH-RP. All three of these peptides were shown to stimulate the steady-state levels of SCF mRNA to a comparable degree. However, the time course of action for GHRH-RP differed markedly from that of GHRH. GHRH-RP and p75-92NH2, similar to GHRH, induce SCF expression, at least in part, via the activation of the protein kinase A/cyclic adenosine monophosphate intracellular signaling pathway.
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PMID:Effects of growth hormone-releasing hormone-related peptide on stem cell factor expression in cultured rat Sertoli cells. 1096 54

The role of cAMP/protein kinase A (PKA)- and tyrosine kinase (TK)-dependent intracellular mechanisms in mediating the action of porcine growth hormone (GH) on insulin-like growth factor I (IGF-I) secretion by porcine ovarian granulosa cells was studied. It was observed that GH-induced stimulation of IGF-I secretion was accompanied by an increase in cAMP production. The stimulation of PKA by the addition of either a cAMP agonist or a phosphodiesterase inhibitor to the medium increased IGF-I release by the cells, indicating a direct stimulation of IGF-I release by cyclic nucleotides. Moreover, the stimulatory effect of GH on IGF-I was completely suppressed by the addition of the PKA blocker Rp-cAMPS. Neither TK blocker altered the basal IGF-I level, but both strongly suppressed the GH-induced increase in IGF-I accumulation. Taken together, these findings suggest that cAMP/PKA- and/or TK-dependent pathways may be involved in the mediation of GH action on IGF-I release by porcine granulosa cells.
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PMID:Presumptive mediators of growth hormone action on insulin-like growth factor I release by porcine ovarian granulosa cells. 1096 59

Cis-unsaturated free fatty acids (FFA) like oleic acid are strong blockers of both basal and stimulated GH secretion in vivo by acting directly on the somatotroph cell. Several lines of evidence suggest that this inhibitory action is the result of a perturbation of the function of several plasma membrane integral proteins. It has been reported recently that cis-FFA are able to block several steps in the inositolphosphates/phospholipase C/Ca2+ (InsPs/PLC/Ca2+) signal transduction pathway triggered by the activation of the TRH receptor. In this paper we present evidence showing that the inhibition of growth hormone (GH) and prolactin (PRL) secretion by cis-FFA in vitro is also exerted at several different levels on the cAMP-protein kinase A (cAMP/PKA) pathway triggered by the stimulation of the vasoactive intestinal peptide (VIP) receptor in pituitary clonal cells. By means of a sequential analysis of signal transduction events, we observed that cis-unsaturated FFA; (1) reduce the activity of adenylate cyclase; (2) perturb the activity of protein kinase A; (3) suppress the VIP-triggered Ca2+ influx, and (4) do not perturb VIP binding or the homologous desensitization of the VIP receptor.
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PMID:Cis-unsaturated free fatty acids block VIP-mediated GH and PRL secretion by perturbing the cAMP/protein kinase A pathway. 1108 Nov 80


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