Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Primates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,513 records · Page 84Linked to original sources
PubMedDate not supplied

Artificial embolization of the middle cerebral artery in primates. Description of an experimental model with extracranial technique.

Artificial embolization of the middle cerebral artery (MCA) was produced in the primate, with a technique similar to that described by Luessenhop and Spence (1960) for the treatment of an inoperable arteriovenous malformation in the territory of the MCA. Silicone spheres (1 to 1.5 mm in diameter) were introduced into the internal carotid artery (ICA) via the external carotid artery (ECA). Emboli (1 to 1.3 mm) passed into the anterior cerebral artery (ACA) in 12%, and into the MCA in 50%. Emboli (1.2 to 1.5 mm) stopped at the ICA bifurcation in 54%. In all primates (82.35%1 in which the emboli occluded the ICA bifurcation or the MCA, immediate contralateral hemiplegia developed. The correlation of the anatomical characteristics of the intracranial vasculature of the ICA bifurcation, the diameter of the emboli, and the anatomical localization of the silicone spheres suggests that this experimental model can produce a selective acute "point" occlusion of the MCA in at least 75% of the cases without violating the cranium, in which the resultant changes in the distribution of water and electrolytes in the brain during the acute ischemic event in the territory of the MCA of the primate can be studied.

Animals↗
PubMed1989

Ascaris suum ova-induced bronchoconstriction, eosinophilia, and IgE antibody responses in experimentally infected primates did not lead to histamine hyperreactivity.

The hypothesis that active immunization of primates to give airway allergic responses would also confer on them a hyperreactivity to a nonspecific stimulus such as histamine was tested in 29 normal rhesus primates. At 6 wk after immunization, specific primate IgE (Rast) to Ascaris antigen had increased from 0.35 +/- 0.17 to 0.98 +/- 0.35 units/ml x 10(2) (p less than 0.05). Histamine released from bronchial alveolar lavage cells in response to antigen increased from 5.4 +/- 0.67 to 24 +/- 1.8ng/10(6) cells (p less than 0.05). In a subgroup of seven animals, airway resistance RL and compliance before and after feeding embryonated Ascaris ova increased from RL 3.5 +/- 3.1 to 275 +/- 212 cm H2O/L/s (p = 0.02) and Cdyn fell from 81 +/- 10 to 11.3 +/- 12 ml/cm H2O (p less than 0.05). The bronchial lavage fluid contained a very high percentage of eosinophils after infection, 8 +/- 3.1 to 24 +/- 13% per 500 cells counted, and did not increase appreciably upon later antigen challenge, 24 +/- 13 to 31 +/- 11% of the cells at 9.5 h after antigen challenge (p = NS). When a group of seven of these 29 animals were compared for their histamine responsiveness before and after acquired Ascaris airway reactivity, there was no difference in 19 animals. Pulmonary response to histamine delivered from freon canisters at doses of 0.005, 0.01, 0.025, and 0.05% did not change (RL, 141 +/- 102 to 93 +/- 62; Cdyn, 49 +/- 7 to 46 +/- 11% change before and after, respectively) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed2004

The squirrel monkey: characterization of a new-world primate model of experimental choroidal neovascularization and comparison with the macaque.

PURPOSE: To evaluate and characterize the New-World squirrel monkey as a primate model for experimental choroidal neovascularization (CNV) studies and to compare it with the current Old-World macaque monkey model. METHODS: Fibrovascular tissues (FVT) were elicited in 12 maculae of seven squirrel monkeys by laser photocoagulation using optimized laser parameters (532 nm, 0.05 second, 75 micro m, 650 mW). Follow-up fundus and fluorescein angiography (FA) examinations were conducted on postlaser days 30 and 35, followed by euthanasia and histologic analysis of tissues. For comparative evaluations, FVT development also was induced and analyzed in eight maculae of four macaque monkeys with laser parameters previously used in this species (514 nm, 0.1 second, 50 micro m, 390 and 455 mW). RESULTS: FVT developed in both primate species, consisting of fibrous tissue that contained vessels that ranged from sparse but identifiable capillaries to well-established neovascular networks. Overall, 65% of the photocoagulation sites in the squirrel monkey and 37% of sites in macaque monkey elicited development of FVT. Localized FVT ranged from modest to extensive thickenings of the choriocapillaris layer. Unexpectedly, 76% of the FVT sites in squirrel monkey eyes and 27% of the sites in macaque eyes showed diffuse FVT that expanded beyond the original photocoagulation sites, accompanied by neovascular infiltration of the retina. CONCLUSIONS: Like the macaque, the squirrel monkey can be considered a useful primate model for experimental CNV investigations, while additionally offering certain species-specific advantages. Diffuse FVT permit studies of antiangiogenic therapies in areas distant from laser photocoagulative trauma sites.

Animals↗
PubMed1979

Regulation of primate testicular luteinizing hormone receptors and steroidogenesis.

The testicular luteinizing hormone (LH) receptors of the rhesus monkey and human have many features in common, including high equilibrium association constant, marked species specificity, and relatively low binding capacity. We have, therefore, used rhesus monkeys as models for human LH-receptor regulation in vivo during gonadotropin treatment. In four adult male monkeys, treated with 10,000 IU human chorionic gonadotropin (hCG), serum and testicular steroidogenic responses were monitored at 24-h intervals during the following 4 d, and LH-receptor concentrations were measured by (125)I-hCG binding to 15,000-g particles prepared from testis biopsy specimens. In treated animals, serum hCG was maximal on day 1 at 322+/-16 ng/ml and declined to 24.4+/-2.3 ng/ml by day 4. Serum testosterone was increased threefold during the subsequent 4 d (from 6.5+/-2.0 to 18.6+/-4.4 ng/ml) but serum progesterone remained unchanged. In contrast, serum 17alpha-hydroxyprogesterone increased 12-fold to 5.5+/-0.5 ng/ml at day 1 and was increased fourfold during the subsequent 3 d. The LH-receptor binding capacity of the primate testis was reduced by 18.3+/-6.0% on day 1, 51.7+/-7.4% on day 2, and 45.3+/-2.4% on day 4. Occupancy of the LH receptors by endogenously bound hCG was significant on day 1 but was negligible by day 4. These data demonstrate that gonadotropin-induced LH-receptor depletion occurs in the rhesus testis and indicate that primate gonadotropin receptors are susceptible to the regulatory processes recently described in the rat. In addition, the simultaneous and disproportionate accumulation of 17alpha-hydroxyprogesterone indicates that 17,20-desmolase was rate-limiting under these conditions in the primate testis Leydig cell.

Animals↗
PubMed1983

Primate erythrocyte-immune complex-clearing mechanism.

Previous in vitro studies have shown that immune complexes (IC) that fix complement can bind to the C3b receptor on primate erythrocytes. The in vivo function of this erythrocyte receptor, however, is unknown. This study was undertaken to determine whether the binding of IC to erythrocytes in vivo might play a role in the removal of IC from the circulation. Baboons and rhesus monkeys were prepared with a catheter in the ascending aorta to infuse IC and in the abdominal aorta, renal, hepatic, and portal veins to monitor changes in binding and clearance of IC across kidney, liver, and spleen + gut, respectively. Autologous 51Cr-labeled erythrocytes were infused intravenously and allowed to equilibrate. Preformed IC (125I-labeled bovine serum albumin [BSA] rabbit anti-BSA) were then infused into the ascending aorta at a constant rate for 120 s. Blood samples were drawn at frequent intervals for 30 min from all catheters below the IC injection site. Each blood sample was then centrifuged on percoll to separate IC bound to erythrocytes from IC in plasma or bound to buffy coat cells. This resulted in an "erythrocyte fraction" beneath the percoll that contained the IC bound to erythrocytes, and a "plasma/buffy coat fraction" above the percoll that contained the IC in plasma and IC bound to buffy coat cells. Analysis of these data showed that the majority of the IC infused into the circulation rapidly became bound to erythrocytes. However, by 5 min after beginning the IC infusion, most of this IC load had been removed from the erythrocytes as they traversed the liver. In contrast, IC on erythrocytes did not deposit in kidney. The IC-bearing erythrocytes themselves were not trapped or detained by any organ. IC in the plasma/buffy coat fraction of blood were removed from the circulation but at a relatively low rate and almost entirely by the liver. These findings suggest that primate erythrocytes intercept large complement-fixing IC in the circulation causing the IC to adhere to the erythrocyte until th e IC-bearing erythrocyte traverses liver where the IC is deposited, and the erythrocyte is returned to the circulation. This primate erythrocyte-IC-clearing mechanism may be important in the protection against diseases mediated by deposition of circulating IC.

Animals↗
PubMed1984

Complement depletion accelerates the clearance of immune complexes from the circulation of primates.

Binding of immune complexes (IC) to erythrocytes in vitro is the result of interaction between C3b sites on the IC, and complement receptors type I (CRI) expressed on primate erythrocytes. Recent evidence indicates that primate erythrocytes can also rapidly bind large, preformed IC in vivo. This study was undertaken to determine if the binding of IC to baboon erythrocytes in vivo is complement dependent and to examine the effect of complement depletion on IC clearance from the circulation. The results indicate that complement depletion in vivo reduced the binding of IC to erythrocytes. There was relatively little binding of IC to leukocytes in both the complement-depleted and complement-repleted condition. Thus, the majority of IC not bound to erythrocytes remained free in the plasma and, consequently, IC infusion during the complement-depleted state resulted in increased plasma IC concentrations. This was associated with a rapid disappearance of IC from the circulation. By contrast, in the normal or complement-repleted state, a large fraction of the IC became bound to erythrocytes during IC infusion, which resulted in lower plasma IC concentrations. Under these conditions, a more gradual rate of disappearance of IC from the circulation was observed. The relatively abrupt clearance of IC from the circulation in the complement-depleted state could not be accounted for by increased hepatic or splenic uptake. These data indicate that, in contrast to previous studies in nonprimates, complement depletion in primates results in accelerated removal of IC from the circulation. This suggests that factors such as hypocomplementemia and deficient expression of erythrocyte CRI, which are known to occur in certain IC-mediated diseases, may promote IC uptake by organs vulnerable to IC-mediated injury.

Animals↗
PubMed1986

Differential binding of immunoglobulin A and immunoglobulin G1 immune complexes to primate erythrocytes in vivo. Immunoglobulin A immune complexes bind less well to erythrocytes and are preferentially deposited in glomeruli.

Primate erythrocytes appear to play a role in the clearance of potentially pathogenic immune complexes (IC) from the circulation. This study was undertaken to compare the clearance from the circulation and tissue uptake of two monoclonal IC probes: one of which, IgG1-IC, was bound well by erythrocytes, the other of which, IgA-IC, was bound relatively poorly by erythrocytes. The IC probes were labeled with different iodine isotopes and infused either concomitantly or sequentially into the arterial circulation. The results indicate that, compared with IgG1-IC, IgA-IC bind less well to primate erythrocytes, are cleared from the circulation more quickly despite their smaller size, and show increased uptake in kidney and lung but decreased uptake in liver and spleen. Evidence is presented which suggests that this pattern of clearance from the circulation and systemic uptake of IgA-IC is the result of decreased binding of IgA-IC to circulating erythrocytes. These findings support the hypothesis that the primate erythrocyte-IC clearing mechanism may be critically important for the safe removal of IC from the circulation.

Animals↗
PubMed1996

Antibodies against CD14 protect primates from endotoxin-induced shock.

Lipopolysaccharide (LPS), residing in the outer membrane of all gram-negative bacteria, is considered a major initiating factor of the gram-negative septic shock syndrome in humans. LPS forms a complex with the LPS binding protein (LBP) in plasma, and LPS-LBP complexes engage a specific receptor, CD14, on the surface of myeloid cells, leading to the production of potent proinflammatory cytokines. The major goal of this study was to test the importance of the CD14 pathway in vivo in a primate model that is similar to human septic shock. Primates were pretreated with one of two different inhibitory anti-CD14 mAbs, then challenged with intravenous endotoxin (375 microg/kg/h) for 8 h. The anti-CD14 treatment regimens were successful in preventing profound hypotension, reducing plasma cytokine levels (TNF-alpha, IL-1beta, IL-6, and IL-8), and inhibiting the alteration in lung epithelial permeability that occurred in animals treated with LPS and an isotype-matched control antibody. These results demonstrate for the first time the importance of the CD14 pathway in a primate model that is similar to human septic shock. Inhibition of the CD14 pathway represents a novel therapeutic approach to treating this life-threatening condition.

Acute Disease↗
PubMed1997

Vitamin D and gonadal steroid-resistant New World primate cells express an intracellular protein which competes with the estrogen receptor for binding to the estrogen response element.

New World primates (NWP) exhibit a form of compensated resistance to vitamin D and other steroid hormones, including 17beta-estradiol. One postulated cause of resistance is that NWP cells overexpress one or more proteins which block hormone action by competing with hormone for its cognate hormone response element. Here we report that both nuclear and postnuclear extracts from NWP, but not Old World primate, cells contained a protein(s) capable of binding directly to the estrogen response element (ERE). This ERE binding protein(s) (ERE-BP) was dissociated from the ERE by excess of either unlabeled ERE or excess of the ERE half-site motif AGGTCAcag. DNA affinity chromatography using concatamers of the latter resulted in > 20,000-fold purification of the ERE-BP. The intensity of the ERE-BP-ERE complex in electromobility shift assay was indirectly related to the amount of wild-type Old World primate estrogen receptor (ER) but not affected when potential ligands, including 17beta-estradiol (up to 100 nM), or anti-ER antibody was added to the binding reaction. We conclude that vitamin D-resistant and gonadal steroid-resistant NWP cells contain a protein(s) that may "silence" ER action by interacting directly with the ERE and interfering with ER binding.

Animals↗
PubMed2001

Periodontal regeneration by FGF-2 (bFGF) in primate models.

We recently demonstrated that a topical application of basic fibroblast growth factor (FGF-2; bFGF) to alveolar bone defects in beagle dogs enhanced periodontal regeneration. The purpose of this study was further characterization of the biological effects of FGF-2 in non-human primates. Thirty-two inflamed furcation class II defects were surgically created in 4 male primates. The gelatinous carrier alone or the carrier containing 0.1 or 0.4% human recombinant FGF-2 was topically applied to the defects and compared with no treatment. Eight weeks after application, the periodontal regeneration in those defects was analyzed. In all FGF-2-treated sites, significant periodontal regeneration was dose-dependently observed in greater amounts than in the carrier-treated or non-treated sites. No instances of epithelial down-growth, ankylosis, or root resorption were observed in the FGF-2-treated sites. These results indicate that a topical application of FGF-2 can enhance considerable periodontal regeneration in surgically created furcation class II defects of non-human primates.

Alveolar Bone Loss↗
PubMedDate not supplied

Urea nitrogen excretion in chair-adapted primates.

To evaluate the temporal pattern of urea excretion in chair-adapted primates (Macaque fascicularis) on continuous total parenteral nutrition (TPN), two groups of five animals were studied. Group I received continuous TPN (75 glucose kcal; 0.56 g nitrogen; and 100 ml fluid per kg per day) while Group II received a single morning isonitrogenous oral meal along with a continuous isovolemic intravenous infusion of 0.45% saline. Urine was collected hourly in group I for 2 days and every 4 hr in group II for 5 days and analyzed for urea content. Time series analysis revealed no periodicity of urea excretion in either group. Six animals were then studied for a total of 46 TPN days to define the relationship between the urea content of a single 3-hr morning urine aliquot and its respective content in a 24-hr collection. A significant linear relationship was found (r = +0.76, p less than 0.01). However, using this relationship, a reasonable estimate (+20%) of measured 24-hr urea output was achieved only 50% of the time using a single 3-hr urea output. Chair-adapted primates maintained on continuous TPN or a single oral meal with continuous saline infusion do not exhibit a periodic pattern of urea excretion. The variability in 3-hr urinary urea output in the chaired primate on continuous TPN does not consistently permit accurate estimation of the coincident 24-hr urinary urea output.

Adaptation, Physiological↗
PubMed2005

Shortened seasonal photoperiodic cycles accelerate aging of the diurnal and circadian locomotor activity rhythms in a primate.

The gray mouse lemur (Microcebus murinus), a prosimian primate, exhibits seasonal rhythms strictly controlled by photoperiodic variations. Previous studies indicated that longevity can be altered by long-term acceleration of seasonal rhythms, providing a model for assessing various aspects of aging. To assess the effect of aging and accelerated aging on the circadian system of this primate, we compared the circadian rhythm of the locomotor activity in adult mouse lemurs (2-4.5 years, n = 9), aged mouse lemurs (5-9 years, n = 10), and adult mouse lemurs that had been exposed from birth to a shortened seasonal photoperiodic cycle (2-4.5 years, n = 7). Compared to adult animals, aged mouse lemurs showed a significant increase in intradaily variability and an advanced activity onset. Aging was characterized by a decrease in amplitude, with both a decrease in nocturnal activity and an increase in daytime activity. When maintained in constant dim red light, aged animals exhibited a shortening of the free-running period (22.8 +/- 0.1 h) compared to adult animals (23.5 +/- 0.1 h). A 3- to 5-year exposure to an accelerated seasonal photoperiodic rhythm ("annual" duration of 5 months) in accelerated mouse lemurs produced disturbances of the locomotor activity rhythm that resembled those of aged mouse lemurs, whether animals were studied in entrained or in free-running conditions. The present study demonstrated a weakened and fragmented locomotor activity rhythm during normal aging in this primate. Increasing the number of expressed seasonal cycles accelerated aging of parameters related to circadian rhythmicity in adult animals.

Aging↗
PubMed2002

Polyclonal long-term repopulating stem cell clones in a primate model.

Hematopoietic bone marrow stem cells generate differentiated blood cells and, when transplanted, may contribute to other organs, such as the brain, heart, and liver. An understanding of in vivo clonal behavior of stem cells will have important implications for cellular and gene therapy. For the first time, we have directly demonstrated the derivation of circulating peripheral blood cells from individual stem cell clones. We analyzed the clonal composition of retrovirus-marked peripheral blood leukocyte populations in 2 different primate models by a novel direct genomic sequencing technique allowing the identification of vector insertion sites. More than 80 contributing long-term hematopoietic clones were identified in individual rhesus macaque peripheral blood transplant recipients and more than 25 different clones in a baboon marrow transplant recipient. Up to 5 insertion sequences from each animal were used to trace the long-term contribution of stem cell clones in these primate models. Continuous and mostly pluripotent contributions of peripheral blood leukocytes from each of the traced clones could be detected for the entire follow-up period of 23 to 33 months. Our study provides direct molecular evidence for a polyclonal, multilineage, and sustained contribution of individual stem cells to primate hematopoiesis.

Animals↗
PubMed2006

alpha4-Integrin(+) endothelium derived from primate embryonic stem cells generates primitive and definitive hematopoietic cells.

The mechanism of commencement of hematopoiesis in blood islands of the yolk sac and the aorta-gonad-mesonephros (AGM) region during primate embryogenesis remains elusive. In this study, we demonstrated that VE-cadherin(+)CD45(-) endothelial cells derived from nonhuman primate embryonic stem cells are able to generate primitive and definitive hematopoietic cells sequentially, as revealed by immunostaining of floating erythrocytes and colony-forming assay in cultures. Single bipotential progenitors for hematopoietic and endothelial lineages are included in this endothelial cell population. Furthermore, hemogenic activity of these endothelial cells is observed exclusively in the alpha4-integrin(+) subpopulation; bipotential progenitors are 4-fold enriched in this subpopulation. The kinetics of this hemogenic subpopulation is similar to that of hemogenic endothelial cells previously reported in the yolk sac and the AGM region in vivo in that they emerge for only a limited time. We suggest that VE-cadherin(+)CD45(-)alpha4-integrin(+) endothelial cells are involved in primitive and definitive hematopoiesis during primate embryogenesis, though VE-cadherin(-)CD45(-)alpha4-integrin(+) cells are the primary sources for primitive hematopoiesis.

Animals↗
PubMed2003

In utero recombinant adeno-associated virus gene transfer in mice, rats, and primates.

BACKGROUND: Gene transfer into the amniotic fluid using recombinant adenovirus vectors was shown previously to result in high efficiency transfer of transgenes into the lungs and intestines. Adenovirus mediated in utero gene therapy, however, resulted in expression of the transgene for less than 30 days. Recombinant adenovirus associated viruses (rAAV) have the advantage of maintaining the viral genome in daughter cells thus providing for long-term expression of transgenes. METHODS: Recombinant AAV2 carrying green fluorescent protein (GFP) was introduced into the amniotic sac of fetal rodents and nonhuman primates. Transgene maintenance and expression was monitor. RESULTS: Gene transfer resulted in rapid uptake and long-term gene expression in mice, rats, and non-human primates. Expression and secretion of the reporter gene, GFP, was readily demonstrated within 72 hours post-therapy. In long-term studies in rats and nonhuman primates, maintenance of GFP DNA, protein expression, and reporter gene secretion was documented for over one year. CONCLUSIONS: Because only multipotential stem cells are present at the time of therapy, these data demonstrated that in utero gene transfer with AAV2 into stem cells resulted in long-term systemic expression of active transgene roducts. Thus, in utero gene transfer via the amniotic fluid may be useful in treatment of gene disorders.

Amniotic Fluid↗
PubMed2003

Immunoexpression of the relaxin receptor LGR7 in breast and uterine tissues of humans and primates.

BACKGROUND: The receptor for the peptide hormone relaxin has recently been identified as the heptahelical G-protein coupled receptor, LGR7. In order to generate molecular tools with which to characterize both in vivo and in vitro expression of this receptor in human and primate tissues, specific monotypic antibodies have been generated and applied to a preliminary analysis of human and primate female reproductive tissues. METHODS: Three peptide sequences were identified from the proposed open reading frame of the cloned LGR7 receptor gene, representing both extracellular and intracellular domains. Two to three rabbits were immunized for each epitope, and the resulting sera subjected to a systematic validation using cultured cells transiently transfected with a receptor-expressing gene construct, or appropriate control constructs. RESULTS: Human and monkey (marmoset, macaque) endometrium showed consistent and specific immunostaining in the stromal cells close to glands. Staining appeared to be more intense in the luteal phase of the cycle. Weak immunostaining was also evident in the endometrial epithelial cells of the marmoset. A myoma in one patient exhibited strong immunostaining in the circumscribing connective tissue. Uterine expression was supported by RT-PCR results from cultured primary endometrial and myometrial cells. Human breast tissue (healthy and tumors) consistently indicated specific immunostaining in the interstitial connective (stromal) tissue within the glands, but not in epithelial or myoepithelial cells, except in some tumors, where a few epithelial and tumor cells also showed weak epitope expression. CONCLUSIONS: Using validated monotypic antibodies recognizing different epitopes of the LGR7 receptor, and from different immunized animals, and in different primate species, a consistent pattern of LGR7 expression was observed in the stromal (connective tissue) cells of the endometrium and breast, consistent also with the known physiology of the relaxin hormone.

Amino Acid Sequence↗
PubMed2004

The use of adolescent nonhuman primates to model human alcohol intake: neurobiological, genetic, and psychological variables.

Traits characteristic of type I and type II alcoholism are thought to relate to dysregulated central nervous system serotonin functioning. In this review, we discuss variables associated with high adolescent alcohol consumption and other risk-taking behaviors in a nonhuman primate model. Adolescent primates with low CSF concentrations of the serotonin metabolite 5-HIAA are more impulsive and exhibit increased levels of alcohol consumption. Both genetic and environmental factors contribute to alcohol-seeking behavior in adolescent macaques. Sequence variation within serotonin system genes, for example, a repeat polymorphism in the transcriptional control region of the monoamine oxidase gene (MAOA-LPR), increases the propensity for adolescent males to consume alcohol. Environmental factors, such as early life stress in the form of peer-rearing or early age of exposure to alcohol, are also associated with increased alcohol consumption. Peer-reared females, especially those exposed to alcohol during early adolescence, exhibit increased rates of alcohol consumption compared to those exposed to alcohol later in development. When genetic variables are also considered, there is an interaction between the low activity serotonin transporter gene promoter s allele (rh5-HTTLPR) and rearing condition on alcohol preference in females but not males, suggesting that the interactions between genes and the environment may be sexually dichotomous. By learning more about the interactions between genes, early experience, and alcohol intake in the adolescent nonhuman primate, we may be able to identify factors that contribute to the susceptibility, pathogenesis, and progression of impulse control disorders, such as alcoholism.

Adolescent↗
PubMed2003

Dynamics of Myc/Max/Mad expression during luteinization of primate granulosa cells in vitro: association with periovulatory proliferation.

Granulosa cell luteinization involves the attenuation of gonadotropin-induced proliferation. Although recent evidence indicates that primate granulosa cells stop dividing within 12 h of an ovulatory stimulus, early events in cell cycle arrest remain unknown. In the current study an in vitro model of primate granulosa cell luteinization is established that allows assessment of early events in terminal differentiation. A luteinizing dose of human chorionic gonadotropin (hCG) results in a secondary rise in proliferation before cell cycle arrest that is paralleled by a transient increase in the expression of c-Myc. In contrast, the c-Myc antagonists Mad1, Mad4, and Mxi1 are transiently repressed by hCG. Max, the common dimerization partner for Myc and Mad, is similarly repressed by hCG, suggesting that changes in the expression of this gene may further regulate the activity of Myc and Mad. To determine whether other cell cycle regulatory families are involved in luteinization, the expression of p53 and the wild-type p53-inducible phosphatase (wip1) was examined. Similar to Mad and Max, p53 and wip1 are transiently repressed by hCG, suggesting that the p53 and Mad pathways have either parallel or cooperative roles in luteinization. Thus, luteinization of primate granulosa cells is preceded by a burst of proliferation that is regulated by changes in the relative levels of c-Myc, Max, and Mad as well as p53.

Animals↗