Biomedical subjects

A R Buckley

Publications and source records attributed to A R Buckley.

At least 55 records · Page 3Linked to original sources

PubMed1995

Nuclear translocation of prolactin: collaboration of tyrosine kinase and protein kinase C activation in rat Nb2 node lymphoma cells.

Recent evidence has suggested that prolactin (PRL), internalized by lactogen-dependent Nb2 lymphoma cells, is actively translocated to the nucleus where it binds to PRL receptors. Moreover, the mitogenic action of PRL in these cells has been separately linked to protein tyrosyl phosphorylation and activation of protein kinase C (PKC). Therefore, the coupling of PRL internalization and nuclear translocation to the activation of these signal transduction pathways was investigated. Results from control experiments indicated that 30% of internalized and 5% total cell-associated 125I-rat PRL could be recovered within nuclei obtained from Nb2 cells previously incubated with the radiolabel for 3 h at 37 degrees C. Furthermore, internalized PRL was found to be intact and not associated with any carrier proteins. Addition of tyrosine kinase (TK) antagonists, genistein or tyrphostin, significantly reduced cell surface binding, internalization, and nuclear translocation of 125I-rat PRL. In contrast, neither the level of cell-associated nor internalized hormone differed between cells treated with the PKC antagonists, staurosporine or calphostin C, and control cultures. Instead, PKC inhibition significantly reduced nuclear PRL translocation. The inhibitory effects of the TK and PKC antagonists on PRL internalization and nuclear translocation in intact Nb2 cells were verified by immunofluorescence microscopy in parallel experiments. In other experiments, each of the kinase inhibitors blocked PRL-stimulated Nb2 cell proliferation in a concentration-dependent manner. It is concluded that activated TK and PKC collaborate in the process of PRL internalization and translocation to the nucleus. TK activation may participate in PRL receptor binding or hormone internalization while activation of PKC appears to be required for its nuclear targeting. Since TK and PKC activation are required for lactogen-stimulated Nb2 cell proliferation, we suggest that a component of the mitogenic pathway in these cells is a direct nuclear interaction of PRL.

Animals↗

PubMed1995

Alterations in splenocyte protein kinase C (PKC) activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vivo.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on growth factor-coupled activation of nuclear protein kinase C (nPKC) and on the subcellular distribution of PKC activity in rat splenocytes were investigated. Seven days after a single injection of TCDD (50 micrograms/kg body weight), cytosolic and particulate PKC activity was significantly higher in splenocytes from TCDD-treated rats or pair-fed control rats compared to ad libitum-fed animals. In a separate experiment, purified splenocyte nuclei from TCDD-treated animals and controls were used to study activation of nPKC by growth factors and other trophic agents. Growth factor-stimulated nPKC activation was attenuated in splenic nuclei from TCDD-treated rats compared to vehicle-treated controls. Evidence presented here suggests that the cellular mechanism of TCDD toxicity leading to immunosuppression in rodents may be mediated in part by uncoupling of growth factor receptors linked to PKC activation at the level of the nucleus. However, changes in total splenocyte PKC activity appear to be correlated with hypophagia since cytosolic and particulate PKC levels were elevated in TCDD-treated rats and their pair-fed partners.

Animals↗

PubMed1995

Color Doppler imaging and spectral analysis of the optic nerve vasculature in glaucoma.

PURPOSE: We used color Doppler imaging to study blood flow velocity in the central retinal artery and the short posterior ciliary arteries in patients with glaucoma. METHOD: Fifty-two patients with chronic open-angle glaucoma, 24 patients with normal-tension glaucoma, and 28 normal subjects were studied. The mean of the peak systolic velocity, the end diastolic velocity, and the resistive index were compared in the three groups. RESULTS: Compared with the normal subjects, the patients with chronic open-angle glaucoma showed a statistically significant (P < .05) decrease in the mean end diastolic velocity and an increase in the mean resistive index in all vessels studied. The patients with normal-tension glaucoma showed similar changes, achieving significance most prominently in the central retinal arteries, compared with normal subjects (P < .05). There were no statistically significant differences between the patients with chronic open-angle glaucoma and those with normal-tension glaucoma. CONCLUSIONS: Open-angle glaucoma appears to be associated with a decreased mean flow velocity and an increased mean resistive index in the ocular vasculature. These changes are in keeping with possibly compromised circulation in this region.

Adult↗

PubMed1995

Rapid induction of pim-1 expression by prolactin and interleukin-2 in rat Nb2 lymphoma cells.

The lactogen-dependent Nb2 lymphoma line (Nb2-11) represents a useful pre-T cell model for investigation of early molecular events coupled to PRL-stimulated cell cycle progression. Expression of pim-1, a protooncogene that encodes a conserved cytosolic serine/threonine protein kinase, is rapidly induced in hematopoietic cells upon mitogen stimulation and is thought to be important for lymphocyte activation. The present study was conducted to determine whether mitogen stimulation in Nb2-11 or lactogen-independent Nb2-SFJCD1 cells provokes pim-1 gene expression. The pim-1 transcript was undetectable in control growth-arrested Nb2-11 cultures; however, PRL rapidly stimulated its expression in a biphasic manner. Peak expression occurred within 2-4 h (> 40-fold) and was followed by a second elevation at 12 h. The effect of PRL and IL-2 to induce pim-1 at 2 h was concentration dependent and not inhibited by cycloheximide. In Nb2-SFJCD1 cells, pim-1 messenger RNA was expressed in control cultures and augmented by PRL stimulation. Results from stability studies indicated that the t1/2 values for the pim-1 transcript were 79 and 81 min in PRL-stimulated Nb2-11 cells at 2 and 12 h. However, in the lactogen-treated Nb2-SFJCD1 line, it was nearly 3-fold more stable (219 min) at 2 h compared to that determined at either 12 h or in unstimulated cultures. In other experiments, PRL-stimulated expression of the pim-1 protein was evaluated in [35S]methionine-labeled cells by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In Nb2-11 cells, enhanced [35S]pim-1 expression paralleled its messenger RNA transcription through 8 h. Elevated [35S]pim-1 was detected within 1 h and peaked by 2-4 h. Therefore, pim-1 represents an immediate early gene induced by PRL stimulation in Nb2-11 cells. Its initial peak of transcription occurs early during G1 cell cycle progression, whereas a second elevation is coincident with the G1/S transition. These results demonstrate that mitogen-induced expression of pim-1 is a rapid event in Nb2 lymphoma cells and suggest that it may be associated with cell cycle progression.

Animals↗

PubMed1995

Rapid activation of mitogen-activated protein kinase and p21ras by prolactin and interleukin 2 in rat Nb2 node lymphoma cells.

Several serine/threonine and tyrosine kinase signal transduction pathways have been recently linked to prolactin (PRL) action in lymphoid cells. Utilizing the lactogen-dependent, rat pre-T lymphoma cell line, Nb2-11, and the autonomous subline, Nb2-SFJCD1, studies were conducted to determine whether PRL- or interleukin-2 (IL-2)-stimulated Nb2 cell proliferation is coupled to the activation of p21ras and mitogen-activated protein (MAP) kinase. Stimulation of Nb2-11 cells, growth-arrested in the early G1 phase of the cell cycle, with PRL or IL-2 rapidly (5-10 min) provoked GTP binding to Ras, enhanced tyrosyl phosphorylation of MAP kinase, significantly increased its enzymatic activity, and caused its nuclear translocation. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), which directly activates protein kinase C, similarly activated Ras and MAP kinase but failed to cause its nuclear translocation. Tyrosine kinase antagonism with genistein inhibited PRL-stimulated Ras and MAP kinase activation. In other experiments, Ras and MAP kinase were each found to be constitutively active in the Nb2-SFJCD1 line. The addition of PRL to these cultures enhanced the activity of these signaling proteins. Finally, the effects of PRL, IL-2, TPA, and phosphatase inhibition on Nb2-11 cell population density and [3H]thymidine uptake were compared. The addition of PRL, IL-2, and TPA significantly stimulated[3H] thymidine incorporation, while only the polypeptide growth factors augmented cell density. Phosphatase inhibition had no effect on either parameter. These results indicate that Nb2 cell proliferation is associated with the early activation of Ras and MAP kinase. Moreover, tyrosyl phosphorylation upstream of Ras activation appears to be required for its subsequent stimulation of mediators, which activate MAP kinase. Protein kinase C activation may be coupled to MAP kinase activation but is not sufficient for Nb2 cell proliferation.

Animals↗

PubMed1994

Prolactin-induced phosphorylation and nuclear translocation of MAP kinase in Nb2 lymphoma cells.

The coupling of prolactin (PRL) receptor ligation to activation of mitogen-activated protein (MAP) kinase was sought in rat Nb2 lymphoma cells, a pre-T lymphocyte line dependent upon lactogens for proliferation. Addition of PRL (20 ng/ml) to Nb2 cells, growth arrested in the early G1 phase of cell cycle, stimulated rapid tyrosyl phosphorylation of MAP kinase (min). Phosphorylated MAP kinase subsequently translocated to the nucleus, with kinetics essentially identical to those demonstrated for nuclear accumulation of PRL. The rapidity of MAP kinase activation suggests an intermediary role for this enzyme in PRL receptor signalling. Moreover, nuclear translocation of MAP kinase provides an interactive mechanism by which PRL, together with its nuclear receptor, may regulate transcription requisite for mitogenesis.

Animals↗

PubMed1994

Diagnosis of peritonsillar abscess: value of intraoral sonography.

OBJECTIVE: Clinical differentiation of peritonsillar abscess from peritonsillar cellulitis can be difficult and often relies on blind needle aspiration of the tonsillar fossa to locate pus. The objective of this study was to establish a noninvasive and reliable sonographic technique for differentiating peritonsillar abscess from peritonsillar cellulitis in equivocal cases and to thereby avoid unnecessary needle aspiration. SUBJECTS AND METHODS: The study population included three healthy volunteers and 18 patients with clinically suspected peritonsillar abscess. The tonsils were assessed by using transcutaneous and intraoral sonography. RESULTS: The tonsils were visualized on both transcutaneous and intraoral sonograms in all three volunteers and in 16 patients. In one patient, the tonsils were not visualized on transcutaneous imaging; intraoral imaging showed cellulitis. In another patient, the intraoral examination was unsuccessful, whereas transcutaneous sonograms showed normal tonsils. On the basis of findings on transcutaneous sonograms, tonsils were considered normal in seven patients. Subsequent intraoral sonograms showed peritonsillar abscesses in four and peritonsillar cellulitis in two. Intraoral imaging was unsuccessful in one patient. On the basis of findings on transcutaneous sonograms, nine patients were thought to have peritonsillar cellulitis. Subsequent intraoral sonograms confirmed cellulitis in four and showed peritonsillar abscess in five. Transcutaneous sonography showed one peritonsillar abscess that was confirmed by findings on intraoral sonography. Surgical confirmation of sonographic findings was obtained in 12 of 18 patients; nine of 10 peritonsillar abscesses had surgical drainage, and three of seven cases of peritonsillar cellulitis had a dry, blind needle aspiration. CONCLUSION: These results show that enlarged tonsils can be visualized with transcutaneous sonography, but intraoral sonography is necessary to adequately define the heterogeneous or cystic nature of a peritonsillar abscess. Intraoral sonography is a useful, simple, and well-tolerated noninvasive technique that can be used to accurately differentiate peritonsillar abscess from peritonsillar cellulitis in clinically equivocal cases. This technique eliminates the need for blind needle aspiration of the tonsillar fossa before surgical drainage. Intraoral sonography also can be used to monitor patients' responses after treatment.

Adult↗

PubMed1994

Suramin, a protein kinase C inhibitor, impairs hepatic regeneration.

Previously we have shown that partial hepatectomy (PH) or exposure of the liver to the mitogen prolactin induces activation of hepatic protein kinase C (PKC). Here, we used suramin, an antitrypanosomal and chemotherapeutic drug which inhibits that enzyme, as a probe of PKC signal transduction in the regenerative response after PH in the rat. Suramin was administered i.p. in nonhepatotoxic doses of 20 to 160 mg/kg 14 days prior to PH. Three measures of hepatic DNA synthesis or cell division, thymidine kinase activity, [3H]thymidine incorporation, and mitotic index were inhibited in a dose-dependent fashion. Baseline PKC activity, in both the cytosolic and particulate fractions, was unchanged by suramin. After PH, PKC activation, signalled by an increase in activity in the particulate fraction, was observed in control rats at 30 and 60 min. However, rats which had previously received suramin demonstrated dose-dependent inhibition of PKC activation. Suramin is known to also disrupt the binding of certain growth factors to their receptors. But if inhibition of PKC activation were conferred by interference with growth factor-receptor binding by suramin, then the generation of diacylglycerol, the second messenger for PKC activation, should likewise be impaired. However, we observed that the diacylglycerol mass generated at 15, 30, and 45 min after PH was not altered by suramin pretreatment. We conclude that the diminution in DNA synthesis after PH by suramin is likely the consequence of direct inhibition of PKC, suggesting that PKC activation is an important, perhaps obligatory, signal transduction event in liver regeneration.

Animals↗

PubMed1994

Neural and endocrine mechanisms of cocaine-induced 70-kDa heat shock protein expression in aorta and adrenal gland.

Cocaine has properties of a physiologic stressor that are reflected by its ability to activate both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. We have previously reported that activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system by restraint and pharmacologic agents induces expression of a set of highly conserved cellular stress response proteins (heat shock proteins, HSP) in the adrenal gland and aorta. In the adrenal gland, HSP expression appears to be mediated by stress-induced increases in adrenocorticotropic hormone whereas expression in the aorta involves noradrenergic neurotransmission. In this report we capitalize on the ability of cocaine to stimulate physiologic stress responses to define further mechanisms regulating HSP70 expression in these tissues. We report the novel observation that cocaine administration induces both adrenal and vascular HSP70 mRNA expression. Elevated HSP70 mRNA was preceded by activation of factors capable of binding to the heat shock transcriptional control element and was followed by an elevation in HSP70 protein. Cocaine significantly increased plasma adrenocorticotrophic hormone whereas hypophysectomy eliminated cocaine-induced expression in the adrenal gland suggesting that in this tissue, the effect of cocaine on HSP70 expression is also mediated via adrenocorticotrophic hormone. In the aorta, depletion of catecholamines by reserpine pretreatment paradoxically augmented cocaine-induced HSP70 expression. Based on these results, it appears that HSP70 expression in the aorta occurs through direct actions of cocaine on vascular cells that are ultimately transduced to activation of the HSP70 gene rather than indirectly through alterations in catecholamine reuptake and release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1993

Effects of intermittent androgen suppression on androgen-dependent tumors. Apoptosis and serum prostate-specific antigen.

BACKGROUND: Since postcastration progression of tumors to an androgen-independent state appears to be linked to the cessation of androgen-induced differentiation of tumorigenic stem cells, the authors hypothesized that the replacement of androgens at the end of a period of apoptotic regression might result in the regeneration of differentiated tumor cells with further apoptotic potential. METHODS AND RESULTS: To determine the effect of intermittent exposure of androgens on the androgen-dependent Shionogi carcinoma, the tumor was transplanted into a succession of male mice, each of which was castrated when the estimated tumor weight became about 3 g. After the tumor had regressed to 30% of the original weight, it was transplanted into the next noncastrated male. This cycle of transplantation and castration-induced apoptosis was repeated successfully four times before growth became androgen-independent during the fifth cycle. In four of Stage C and three of Stage D patients with prostate cancer, androgen withdrawal was initiated with cyproterone acetate (100 mg/d) and diethylstilbestrol (0.1 mg/d) and then maintained with cyproterone acetate in combination with the luteinizing hormone-releasing hormone agonist, goserelin acetate (3.6 mg/month). After 6 or more months of suppression of serum prostate-specific antigen (PSA) into the normal range, treatment was interrupted for 2 to 11 months. After recovery of testicular function, androgen-withdrawal therapy was resumed when serum PSA increased to a level of about 20 micrograms/l. This cycle was repeated sequentially to a total of two to four times over treatment periods of 21 to 47 months with no loss of androgen dependence. CONCLUSIONS: These results demonstrate that intermittent androgen suppression can be used to induce multiple apoptotic regressions of a tumor; they also suggest that the cyclic effects of such treatment on prostate cancer can be followed by the sequential measurement of serum PSA levels.

Adenocarcinoma↗

PubMed1993

Inhibition by genistein of prolactin-induced Nb2 lymphoma cell mitogenesis.

Tyrosine kinase activation in mediating the mitogenic action of prolactin (PRL) has been evaluated. Use was made of genistein, a tyrosine kinase antagonist, and cultured rat Nb2 lymphoma cells, i.e. the lactogen-dependent Nb2-11 line and a lactogen-independent subline, Nb2-SFJCD1. Genistein was found to be a potent growth-inhibitor for both lines, inhibiting 3H-thymidine incorporation in Nb2-11 and Nb2-SFJCD1 cells with IC50s of 4.2 and 6.7 micrograms/ml, respectively. Genistein also inhibited expression and translation of the heat shock protein 70 gene and pp40 protein substrate phosphorylation which, in Nb2-11 cells, followed PRL addition within minutes. Genistein inhibition of DNA synthesis in G1-arrested Nb2-11 cells was most pronounced if the agent was added within 1 h of PRL treatment. The results indicate that, while both Nb2 cell lines have a general growth requirement for tyrosyl phosphorylation, the early, PRL-induced tyrosine kinase activation is a component of the PRL mitogenic signal transduction pathway.

Animals↗

PubMed1993

Dopaminergic regulation of heat shock protein-70 expression in adrenal gland and aorta.

The induction of heat shock proteins (HSPs) by cellular stress and activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system by physiological stress are biological responses that aid in the maintenance of cellular and organismal homeostasis, respectively. Based on previous studies, we have hypothesized that HSPs play a functional role in neural and endocrine stress response mechanisms in mammalian organisms. To determine the endocrine and/or neural components regulating stress-induced HSP70 expression in vivo, we have employed the long-acting synthetic propylergoline dopamine agonist CQP 201-403 (CQP). We report the novel observation that CQP mimics the effect of restraint stress to induce HSP70 expression in both adrenal gland and aorta of the rat. The presence of CQP-induced HSP70 mRNA and protein was preceded by the activation of a protein factor capable of binding to the heat shock transcriptional control element. CQP-induced HSP70 expression in the adrenal gland was restricted to the cortex, as previously observed in restraint-stressed animals. However, the distribution of expression among the three cortical layers was distinct. Hypophysectomy virtually eliminated the effects of CQP on the adrenal gland and markedly reduced HSP70 induction in the aorta. Collectively, these results provide evidence that dopaminergic systems contribute to the physiological regulation of HSP70 expression in adrenal gland and aorta directly through actions on receptors in responsive tissues and/or indirectly through the release of pituitary hormones.

Adrenal Cortex↗

PubMed1993

Nuclear co-localization of prolactin and the prolactin receptor in rat Nb2 node lymphoma cells.

Previous studies have indicated that prolactin (PRL) interacts with specific, high affinity, immunoreactive binding sites within isolated rat hepatocyte nuclei. Moreover, endogenous PRL appears to be bound to this site. However, it remained important to demonstrate nuclear PRL receptors and hormonal translocation in an intact cell system. Therefore, we sought nuclear translocation of PRL and its receptor in the nucleus of PRL-dependent Nb2 node lymphoma cells. Utilizing immunofluorescence (IF) microscopy, growth-arrested cells were found to constitutively express the PRL receptor in the nucleus and in the membrane/cytosol compartments. Addition of PRL stimulated rapid hormone internalization followed by translocation to the nucleus within 6-12 hrs. The translocation of PRL was found to be reversible and dependent upon ATP. These results indicate that an early event coupled to the mitogenic action of PRL in Nb2 cells is hormone transport to the nucleus during the G1 and S phases of cell cycle. Once in the nucleus, PRL bound to its receptor may directly influence gene transcription.

Adenosine Triphosphate↗

PubMed1992

Identification of prolactin receptors in hepatic nuclei.

Prolactin is a trophic hormone which may act directly at the hepatocyte nucleus. In this study, specific prolactin binding sites were sought in purified rat liver nuclei. Saturable and specific, high affinity 125I-prolactin binding sites were demonstrated to be on or within the nucleus. Prolactin binding was competitively inhibited by rat and ovine prolactins but not by rat growth hormone. Using immunogold electron microscopy, we detected prolactin receptors throughout the nucleus, in association with heterochromatin. Furthermore, endogenous immunoreactive prolactin was demonstrated to be within hepatic nuclei. We conclude that rat liver nuclei possess prolactin binding sites which likely participate in hormone-directed growth processes.

Animals↗

PubMed1992

Real-time sonography in ocular trauma.

Real-time sonography was evaluated retrospectively in 71 consecutive patients with ocular trauma. A total of 51 vitreous hemorrhages, 20 hemorrhages in the anterior chamber, 22 retinal detachments, seven choroidal detachments, five foreign bodies, and 12 dislocated lenses were identified sonographically. In 10 instances (three choroidal detachments, six retinal detachments, and one lens dislocation), these sonographic findings were not apparent on clinical examination. One hemorrhage of the anterior chamber was missed on sonography. Both sonography and clinical examination failed to visualize one retinal detachment. The results of this study show that real-time sonography is valuable in the assessment of ocular trauma and supplements clinical examination with valuable information.

Adult↗

PubMed1992

Venoocclusive liver disease after bone marrow transplantation: findings at duplex sonography.

Ascites, thickening of the gallbladder wall, and reversal of portal flow are documented sonographic findings in venoocclusive disease of the liver. The frequency and specificity of these findings and their relationship to the severity of this disease have not been studied. In an attempt to clarify these issues, 65 patients who had bone marrow transplantations were prospectively studied with serial B-scans and duplex color Doppler sonography. For all patients, assessment included liver size and texture, thickening of the gallbladder wall (greater than 10 mm), and presence of ascites. Doppler flow velocity profiles were obtained from the portal vein, hepatic veins, and inferior vena cava. The hepatic artery resistive index (RI) was calculated. Twenty volunteers were also studied to establish normal flow values. Nineteen patients had documented venoocclusive disease, nine had hepatic graft-vs-host disease (GVHD) (five after proved venoocclusive disease), two had hepatitis, and 40 had no clinical or biochemical evidence of liver injury after bone marrow transplantation. Ascites (n = 16), thickening of the gallbladder wall (n = 8), hepatomegaly (n = 8), and altered liver texture (n = 3) were not distinguishing features of venoocclusive disease. Mean hepatic artery RI was as follows (ranges are in parentheses): control group, 0.69 (0.58-0.76); venoocclusive disease patients, 0.81 (0.75-0.87); GVHD patients, 0.69 (0.63-0.71); all other patients after bone marrow transplantation, 0.66 (0.61-0.71). The RI values in venoocclusive disease were significantly elevated, but an incremental rise in RI with increasing severity of the disease was not seen. Abnormalities in portal vein flow were seen in only two patients: in one with fatal venoocclusive disease, reversed portal flow developed, and in one with GVHD, portal vein thrombosis developed. Contrary to previous reports, no correlation between abnormalities in portal flow and venoocclusive disease was seen. Flow velocities in the hepatic veins and the inferior vena cava were not significantly different from values in the volunteer group. These results suggest that a significant elevation of the hepatic artery RI may be a sensitive index of liver damage related to venoocclusive disease after bone marrow transplantation and an important distinguishing sonographic feature.

Blood Flow Velocity↗

PubMed1991

Prolactin-provoked alterations of cytosolic, membrane, and nuclear protein kinase C following partial hepatectomy.

The adenohypophyseal polypeptide hormone prolactin is a potent liver mitogen, stimulating cell cycle progression, an effect that appears coupled to increasing protein kinase C activity in membrane and nuclear fractions. Here, we examine whether hepatocyte proliferation, stimulated by partial hepatectomy, is associated with altered serum prolactin or protein kinase C activation. Within 5-15 min of liver resection, serum prolactin concentrations elevate significantly. Protein kinase C activity in hepatic cytosol decreases significantly, and membrane and nuclear PKC activity increase by 30 min. Hypophysectomy prior to partial hepatectomy abrogates any effect of liver resection on protein kinase C activation in the hepatic remnant. Based upon these data, it is suggested that the rapid increase in serum prolactin seen after partial hepatectomy may be linked to protein kinase C activation, which in turn stimulates the hepatic proliferative response that is essential for hepatic regeneration.

Animals↗

PubMed1991

Prolactin-stimulated ornithine decarboxylase induction in rat hepatocytes: coupling to diacylglycerol generation and protein kinase C.

The trophic effects of prolactin (PRL) in rat liver have been linked to activation of protein kinase C (PKC). Since alterations in PKC activity imply its activation by 1,2-diacylglycerol (DAG), we tested whether PRL treatment stimulated DAG generation coupled to induction of a growth response in primary hepatocytes. Addition of PRL to hepatocyte cultures significantly increased [3H]-glycerol incorporation into DAG within 5 minutes which was followed by a loss of cytosolic PKC activity by 10 minutes. Prolactin also significantly enhanced radiolabel incorporation into triacylglycerol and phospholipids within 10 minutes and induced ODC activity at 6 hours. Therefore, prolactin-stimulated alterations in PKC activity are preceded by enhanced DAG generation. Moreover, these events appear to be coupled to PRL-stimulated entry of hepatocytes into cell cycle.

Animals↗