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PubMed1998

Taste preference in nonhuman primates to compounds sweet in man.

Primates have stimulated more interest than any other group as humans are ranked in this same mammalian order. Gustatory responses of human and nonhuman primates have already been compared for compounds such as monosaccharides, oligosaccharides, polyols, amino acids, dipeptides, proteins, dihydrochalcones, sulfamates, saccharin, acesulfame, diterpenes or urea derivatives, all known to be sweet in man. But no rational comparison in primates has been attempted. Using a structure-activity relationship study in primates, it is now possible to classify the primate sweetness receptors into four types according to the behavioral responses observed from various selected compounds sweet in humans. The four types are represented by (1) the Callitrichidae and (2) the Cebidae, both from the infraorder Platyrrhini (New World monkeys), (3) the Lemuridae and Lorisidae, from the suborder Prosimii (prosimians), and (4) the Cercopithecidae (Old World monkeys), Hylobatidae (lesser apes), Pongidae (great apes), and Hominidae (humans) from the infraorder Catarrhini (Old World simians). By a comparative study of the putative receptor recognition sites postulated for each type of receptor, it is inferred that the Callitrichidae (marmosets and tamarins) have retained the most primitive sweetness receptor among primates. As we believe that the evolution of the sweetness receptor is a key factor involved in the raising of nonhuman primates from a 'primitive grade' towards a more 'advanced' or 'simian grade,' the possible phylogenetic implications of these findings will be discussed.

Animals↗
PubMed1998

Human endogenous retrovirus K homologous sequences and their coding capacity in Old World primates.

The coding capacity for retroviral Gag and Env proteins has been maintained in human endogenous retroviruses of the HERV-K family. HERV-K homologous sequences have been found in all Old World primates. Here, we examined Old World primate species for the presence of full-length HERV-K gag and env genes and the presence of gag and env open reading frames as determined by the protein truncation test. Full-length HERV-K env genes were found in DNAs of all Old World primate species, whereas open reading frames for Env protein were found solely in human, chimpanzee, and gorilla DNAs. The mutational event leading to two HERV-K types was found to have occurred after the separation of hominids from lower Old World primates and before the expansion of hominids. Full-length HERV-K gag genes in hominids displayed a 96-bp deletion compared to those in lower Old World primates. The ancient gag variant has not been maintained during hominid evolution. Open reading frames for HERV-K Gag have been found in all Old World primates except chimpanzees. Our study of the HERV-K family during Old World primate evolution contributes to the understanding of their possible biological functions in the host genomes.

Animals↗
PubMed1990

Development and regulation of growth and differentiated function in human and subhuman primate fetal gonads.

We have attempted to summarize the research on primate fetal gonadal development that has occurred over the past three decades. Many similarities exist between fetal gonadal development in human and subhuman primates; therefore, comparisons and analogies between these species can be made. Fetal gonadal development is a complex process dependent on timely maturation and differentiation of several cell types with different functions. Adequate development is important for normal sexual development and intact adult fertility potential as well as for intrauterine priming of neural centers in the central nervous system. While the fetal primate testis is active in steroidogenesis, the fetal ovary seems to be quiescent throughout most of gestation, although some ovarian steroidogenic enzymes have been demonstrated. Growth and development of both gonads are controlled during late gestation at least in part by pituitary hormones, while earlier in gestation other yet undefined regulators (placental, intragonadal) likely also are active. The main goal of this review was to demonstrate that gonadal growth and differentiation, both in males and females, is regulated by endocrine factors as well as by intragonadal, autocrine/paracrine agents. Although many parts of the puzzle are still missing it is probable that, similar to fetal development of other endocrine tissues and to events in postnatal gonads, these local regulators have important functions. Currently, primate fetal gonadal research is lacking in at least two key aspects: 1) the definition of paracrine and autocrine nonsteroidal factors that are involved in the regulation of gonadal growth and differentiation in vitro; and 2) in vivo studies in subhuman primates that might better help to clarify the biological roles of the multiple extra- and intragonadal hormones and their complex interactions. To date, the regulation of gonadal steroidogenesis has been investigated more thoroughly than the regulation of gonadal growth. Most of our knowledge stems from observations of gonadal development in anencephalics or subhuman primates after pituitary ablation. Because of the constraints of small organ size and limitation of material, studies of fetal primate gonadal development have been limited. Given such limitations, new molecular biological techniques, including polymerase chain reaction and in situ hybridization, may provide the means of addressing these questions. Further, because of these limitations, sensitive cell separation techniques need to be developed to achieve enriched primary gonadal cell cultures from individual gonads.

Animals↗
PubMed1986

Cortisol levels, binding, and properties of corticosteroid-binding globulin in the serum of primates.

New World primates have exceptionally high plasma levels of cortisol and other steroid hormones when compared with humans and other primates. It has been suggested that this difference can be explained by either low affinity or concentration of cellular steroid receptors. We have assessed cortisol availability in serum from several species of New and Old World primates under physiological conditions (whole serum at 37 degrees C). Measurements were made of total and free cortisol, corticosteroid-binding globulin (CBG) binding capacity and affinity for cortisol, distribution of cortisol in serum, and its binding to albumin. In agreement with earlier reports, plasma free cortisol levels in Old World primates, prosimians, and humans range from 10-300 nM. However, very high total plasma cortisol together with low CBG binding capacity and affinity result in free cortisol concentrations of 1-4 microM in some New World primates (squirrel monkey and marmosets) but not in others such as the titi and capuchin. In squirrel monkeys, free cortisol levels are far greater than might be predicted from the affinity of the glucocorticoid receptor estimated in cultured skin fibroblasts. In addition to low affinity, CBG from squirrel monkeys and other New World primates exhibits differences in electrophoretic mobility and sedimentation behavior in sucrose density ultracentrifugation, suggestive of a molecular weight that is approximately twice that of CBG from other species. Together with other data these results indicate that the apparent glucocorticoid resistance found in New World primates is a complex phenomenon that is not easily explained by present concepts of glucocorticoid action.

Animals↗
PubMed1989

The comparative anatomy of the forelimb veins of primates.

One hundred and thirteen forelimbs taken from 62 individuals belonging to 17 primate genera were dissected to reveal the entire course of the superficial venous system. The course of the deep venous system was also documented in at least one forelimb of each primate genus, and the number and location of perforating veins was recorded in 18 human and 45 non-human primate limbs. In Pan, Gorilla and in about 25% of human specimens the lateral superficial vein was confined to the forearm, while in all other primates, and in the majority of humans, this vein extended from the carpus to the clavicular region. Only Pongo and humans exhibited a second main superficial vein on the medial side of the forearm. In all primates the deep veins of the forelimb usually accompanied the arteries. Thus variation in the deep venous system reflected the different arterial patterns exhibited by these primates. The number of perforating veins in the forelimb was related to the length of the limb. Primate genera with longer forelimbs had more perforators, though not as many as would be expected if the number of perforators scaled linearly with limb length.

Animals↗
PubMed1987

Genetic significance of some common primate models in biomedical research.

Nonhuman primates are excellent animal models for human diseases because of their close relationship to humans. Indeed, comparisons of the chromosomes and DNA homologies between primates and humans testify to the commonality of the genetic material between these phylogenetically related species. Not surprisingly, this close relationship at the genotypic level extends to the phenotypic level. Thus, the patho-physiological responses of humans and nonhuman primates to internal and external insults are remarkably similar. Two types of human diseases for which nonhuman primates are paramount animal models are discussed. One type includes diseases with defined, single agent etiologies and to which all members of the species are genetically susceptible. Examples of these are leprosy, AIDS, hepatitis and Parkinson's disease. A second type represents diseases that have a substantial genetic component, but are multifactorial and are greatly influenced by the environment. Examples of these are diabetes, lymphoma, atherosclerosis, alcoholic cirrhosis and anxiety disorders. Nonhuman primates are also ideally suited to the role of animal models in the new area of human gene therapy. In the future, biomedical research will focus increasingly on genetic manipulations such as the transfer of genes from one individual to another to correct genetic diseases, particularly those diseases caused by single recessive gene defects. Before gene transfers are attempted in humans, they should be done in nonhuman primates. In a real sense, nonhuman primates, as animal models, represent the "step to man."

Animals↗
PubMed1982

Enteric viruses of nonhuman primates.

The phylogenetic relationship of nonhuman primates to man implies that many of these animals could serve as surrogates for studies of diseases of man. Many nonhuman primate species are susceptible not only to viruses of human origin but also to nonhuman primate viruses that are counterparts of viruses of man. All monkeys and great apes do not respond similarly to an antigenic stimulus. Some agents are highly pathogenic for one species and completely innocuous for another. For example, poliovirus causes disease and fatalities in great apes, but picornaviruses given orally cause few lesions in most nonhuman primates. Other enteroviruses (coxsackie-, echoviruses) have caused disease in nonhuman primates. It is difficult to separate viruses into distinct categories according to their anatomic affinities. Many viruses not considered to be enteric may be recovered from the intestinal tract. Adenoviruses, both human and nonhuman strains, which are not considered enteric viruses, nonetheless are recovered frequently from the intestinal tract. Adult animals show little evidence of disease, with the possible exception of diarrhea, after adenovirus infection. Newborns, however, may respond with a fatal pneumoenteritis. Adenovirus may be associated with diseases in organs other than the intestines. The reoviruses, which may be recovered from the intestinal tract, also are generally innocuous. Rotaviruses as pathogens in nonhuman primates are presently under study, and it is suspected that rotaviruses of man may produce experimental disease in nonhuman primates. Production of diabetes by several of the enteric viruses has been suggested but not demonstrated conclusively.

Adenoviruses, Simian↗
PubMed1998

Evolutionary and ecological implications of primate seed dispersal.

In this paper, we evaluate patterns of fruit eating and seed dispersal in monkeys and apes and draw an important distinction between 1) the ecological consequences of primates as seed dispersers and 2) the evolutionary implications of primates on the seed and fruit traits of the plant species they exploit. In many forest communities, primates act as both seed predators and seed dispersers and are likely to have an important ecological impact on patterns of forest regeneration and tree species diversity. Evidence from Kibale National Park, Uganda, and Manu National Park, Peru, as well as several other South American sites indicates that monkeys and apes display a wide range of fruit-processing behaviors, including spitting seeds, dropping seeds, masticating seeds, and swallowing seeds. Differences in consumer body size, diet, ranging patterns, and oral and digestive morphology result in different patterns in the distance and distribution of seeds from the parent plant. In the case of South American monkeys, for example, despite their relatively small body size, platyrrhines were found to exploit larger fruits and swallow larger seeds on average than did Old World monkeys and apes of the Kibale forest. We found little evidence to support the existence of a coevolutionary relationship between a single or set of primate dispersers and the particular plant species they disperse. This is due to variability in the manner in which monkeys and apes select fruits and treat seeds, the fact that many species of primates and nonprimates exploit and disperse the same fruit species, and the fact that extremely high levels of postdispersal seed, seedling, and sapling mortality serve to dilute the influence that any primate species may have on the recruitment of the next generation of adult trees. It is apparent that many primate lineages exhibit dental, digestive, and/or sensory adaptations that aid in the exploitation of particular food types and that many lineages of flowering plants have evolved characteristics of fruits and seeds that facilitate seed dispersal. However, in light of currently available data, we argue that these represent evolutionary rather than more strictly defined coevolutionary relationships.

Animals↗
PubMed1990

Organization of cytochrome oxidase staining in the visual cortex of nocturnal primates (Galago crassicaudatus and Galago senegalensis): I. Adult patterns.

The distribution and differential staining patterns of cytochrome oxidase (CO) activity in visual cortical areas have provided useful anatomical markers for the modular organization of area 17 (striate cortex) and area 18 in primates. In macaque and squirrel monkeys, previous studies have shown that the majority of cells that lie in areas of high CO activity are color selective, are nonoriented, and project to adjacent zones of high CO activity in area 17 and to stripes of high CO activity in area 18. By contrast, most cells in zones with weak CO activity in area 17 have relatively narrow orientation tuning and are not color selective (Livingstone and Hubel: J. Neurosci. 4:309-356, 2830-2835, '84; 7:3371-3377, '87). The periodic organization of CO activity in area 17, the "blobs," and the stripe-like organization in area 18 thus seem to define visual cortical processing modules and/or channels in primates. We have investigated the organization of CO activity in areas 17 and 18 in two species of nocturnal prosimian primates [Galago crassicaudatus (GCC) and Galago senegalensis (GSS)] in order to evaluate CO staining patterns in primates that have been reported to possess almost exclusively rod retinae and no color vision. In area 17 of both species, our results show that, as in diurnal and nocturnal simian primates, the darkest CO staining occurs in layers III and IV, with clear periodicity in layer III (i.e., CO blobs) and homogeneous staining in layer IV beta, the cortical recipient sublayer of the geniculate parvocellular layers. In GCC, individual blobs in layer III appear to be larger and less frequent than has been reported for the macaque monkey. Unlike simian primates, both galago species exhibit clear CO periodicities within layer IV alpha, the cortical recipient sublayer of the magnocellular geniculate layers. In addition, faint CO periodicities are apparent in layer VI and scattered large darkly CO stained pyramidal cells are visible throughout layer V. Quantitative analysis suggests that CO periodicities are more frequent in GSS than in GCC, suggesting that there may be evolutionary pressure to maintain the same number of CO modules within the smaller striate cortex of the lesser galago, although this is not the trend found across distantly related species. CO activity in area 18 is less well-developed than reported in other primates. In fact, we could not reliably identify discontinuities in CO staining in area 18 of GSS.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Identification of a competitive binding component in vitamin D-resistant New World primate cells with a low affinity but high capacity for 1,25-dihydroxyvitamin D3.

Monkeys in a number of different New World primate genera express a form of compensated target organ resistance to steroid hormones, including 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Characterization of these phenotypes has previously relied upon the study of the 1,25-(OH)2D3-receptor (VDR) interaction in cultured dermal fibroblasts from affected primates. In this report, we show that three of these prototypic phenotypes can be faithfully reproduced in previously established cultured cell lines: B95-8, EBV-transformed B lymphoblasts from the marmoset (Callithrix jacchus), a New World primate with recognized vitamin D resistance; OMK, renal tubular epithelial cells from the owl monkey (Aotus trivergatus), a New World primate with an Old World primate-like VDR phenotype; and MLA144, transformed B lymphoblasts from a gibbon (Hylobates), an Old World primate that expresses the wild-type VDR phenotype. The rank order of specific nuclear uptake and binding of [3H]1,25-(OH)2D3 to the VDR was OMK > or = MLA144 >> B95-8. Despite a 7- to 9-fold difference in cellular VDR content according to ligand binding analyses, there was no discernible difference in the internalization constant Kin for specific cellular uptake of [3H]1,25-(OH)2D3 (0.12-0.26 nM) or in the quantity of VDR detected by immunoblot analysis. We now speculate that the discrepancy in VDR quantitation by binding and immunoblot analysis in the B95-8 New World primate cell line results from the presence of an intracellular, vitamin D metabolite binding moiety in this cell line that competes with the VDR for metabolite binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The interrelationship of lens anatomy and optical quality. II. Primate lenses.

We have quantified the influence of lens sutural anatomy on optical quality (focal length variability, i.e. spherical aberration) in adult monkeys (Macaque nemestrina). Adult lenses (n = 6) were initially scanned by a low-power helium-neon laser beam that was passed at a series of acute angles to, and/or directly through, lens sutures. Optical analysis showed that while the 'star' sutures of primate lenses exerted a quantifiable negative effect on focal length variability, this detrimental effect was far less significant than that attributable to 'line' and 'Y' sutures in non-primate lenses. Correlative morphological and 3-D computer-assisted drawing (CAD) analysis of the laser-scanned lenses areas, as well as of variably aged lenses (n = 30), revealed that primates have a more complex lens architecture than non-primates. Non-primate lenses feature suture planes, aligned along the visual axis that are responsible for a significant quantifiable increase in spherical aberration. Primate lenses are characterized by an absence of continuous suture planes aligned along the visual axis. Rather, 3-D-CADs of primate lenses demonstrate that distinct generations of progressively more complex sutures are produced as a function of development, growth, and age. In succession, 'Y' sutures (three branches) are formed throughout embryonic development, 'simple star' sutures (three-six branches) evolve after birth and through infancy, 'star' sutures (six-nine branches) are made in young adult lenses and, finally, 'complex star' sutures (nine-15 branches) are laid down from middle through old age. In view of the fact that slit-lamp evaluation of cataractous lenses often reveals abnormally thin zones of discontinuity, it is significant to note that the temporal development of the zones of discontinuity in normal human lenses is essentially identical to the progressive iteration of offset monkey lens sutures. In conclusion, these studies describe a specific structural aspect of lenses that adversely influences optical quality, and relates it to the most commonly employed clinical technique to identify and monitor the progress of cataracts.

Aging↗
PubMed1985

Definition of the T-lymphocyte inducer of suppression in primates using a monoclonal antibody.

Since some of the conserved antigens between man and phylogenetically lower primate species may be more immunodominant on lymphocytes of the lower primate species, we reasoned that immunization of mice with lymphocytes from lower primates might prove a useful strategy for developing monoclonal antibodies which recognize functionally important structures on both human and nonhuman primate lymphocytes. In employing this approach for the development of monoclonal antibodies, we have developed the antibody anti-2H4 which recognizes a structure on both T on non-T mononuclear cells of a wide array of primate species. 2H4+ rhesus monkey T lymphocytes exhibited a greater proliferative response to lectin and alloantigenic stimulation than 2H4- cells, suggesting that anti-2H4 might separate primate T lymphocytes into functionally distinct cell populations. In fact, helper activity for antibody production by rhesus monkey B lymphocytes in response to pokeweed mitogen (PWM) resided in the 2H4- T-cell population. Furthermore, the 2H4+ T-lymphocyte population activated the suppressor function of T8+ rhesus monkey cells. The fact that the surface antigen which defines this T-cell subset is widely conserved in nonhuman primates suggests that anti-2H4 recognizes a functionally important structure.

Animals↗
PubMed1978

MAC-1, a new genetically transmitted type C virus of primates: "low frequency" activation from stumptail monkey cell cultures.

A new class of endogenous primate type C virus has been isolated from a continuous tissue culture line of Macaca arctoides cells by co-cultivation with a human cell line. The virus, designated MAC-1, can be transmitted to human and feline cells in tissue culture, and is unrelated, by immunological and nucleic acid hybridization criteria, to previously characterized retroviral isolates of primates. In particular, MAC-1 shows no detectable homology to the baboon type C viruses, even though viral genes related to the latter group are readily detected in M. arctoides cellular DNA. Viral gene sequences related to the MAC-1 genome are present in multiple copies (50-150 per haploid genome) in Old World primates, and are expressed in the cellular RNAs of uninfected and "virus-free" primate cells and tissues. Thus there are at least two distinct sets of genetically transmitted Old World primate type C viral genes, each of which is found in multiple copies in normal primate cellular DNA. With the description of this new retrovirus, there are now a minimum of five distinct genetically transmitted viruses of primates, three type C and type D, each represented in multiple copies in the normal cellular DNA.

Animals↗
PubMed1998

Screening for antiproliferative actions of mifepristone. Differential endometrial responses of primates versus rats.

This laboratory has previously shown the capability of the antiprogestin, mifepristone, to noncompetitively inhibit estrogen-induced endometrial proliferation in nonhuman primates. In the following study, use of the rat uterine weight bioassay was compared against a primate (Macaca fascicularis) uterine bioassay to identify the noncompetitive/antiproliferative effects of mifepristone. These uterine bioassays were contrasted for reasons of identifying a comparative laboratory rodent model that could substitute for the need to use primate models in the screening of potential antiprogestins, thereby saving time, cost, and primate resources. Results of the primate experiment showed that mifepristone decreased endometrial proliferation in a dose-dependent manner; importantly, this decrease occurred in the presence of sustained physiologic serum 17 beta-estradiol (E2) levels. However, in the rat model, results showed that mifepristone altered uterine wet weight and blotted weight values only in those animals receiving pharmacological doses of E2 (p < 0.05). Based on the results summarized herein, use of this rat uterine weight bioassay as a substitute for primate models is not recommended for screening and identification of "interesting" antiprogestins. Apparently, the endometrial noncompetitive antiestrogenic/antiproliferative effects of mifepristone, observed repeatedly in these laboratory primates, do not operate in the rat uterine tissue.

Animals↗
PubMed1998

Origin and evolution of Asian hominoid primates. Paleontological data versus molecular data.

The origin and evolution of hominoid primates (apes and man) has long been studied exclusively on the basis of available fossil remains. Indeed, a migration of African primates towards Asia at about -16 to -17 Ma might have given the lineage of Miocene Asian hominoids. This hypothesis is supported by the oldest remains of Miocene Asian hominoids dated at about -16.1 Ma. But the recent discovery of anthropoid primates in the Eocene of Asia seems to indicate that Asia was a major evolutionary and differentiation centre for anthropoid primates as early as the Eocene. In addition, Asian primates probably continued to evolve in Asia from the Eocene onward and led at least to the extant Asian hominoids (orangutans and gibbons). African and Asian extant anthropoid primates might therefore have diverged at least 36 Ma ago, and this hypothesis is also supported by the most recent data in molecular biology. Moreover, an Asiatic origin of African Paleogene propliopithecine primates is suggested. In that context, evolutionary rates might not be constant, and molecular clocks should be necessarily characteristic for each studied group of mammals. Several examples that illustrate the conflict between paleontological and molecular data are discussed. The necessity to integrate more systematically paleontological data as chronological reference points in studies in molecular phylogeny is discussed.

Animals↗
PubMed1997

Comparative study of target antigens for primate xenoreactive natural antibodies in pig and rat endothelial cells.

BACKGROUND: A rat-to-primate cardiac xenograft model has been proposed as an alternative to the clinically relevant but more cumbersome pig-to-primate model for assessing the efficacy of strategies aimed at preventing xenograft hyperacute rejection. As in pig xenografts, the rejection of rat hearts was mediated by the binding of xenoreactive natural antibodies (XNA) and complement activation. The present study was conducted to identify target antigens recognized by cynomolgus and rhesus monkey IgM XNA on rat tissues and cells in comparison with pig cells. METHODS: The reactivity of rhesus or cynomolgus serum on pig and rat endothelial cells (ECs) was studied by flow cytometry, ELISA, and complement-dependent cytotoxicity, after removal of primate XNA by perfusion of pig livers, immunoadsorption on a Gal alpha(1,3)Gal affinity column, and enzymatic removal of alpha-galactosyl epitopes from the cell surface. Rat and pig EC extracts were also immunoprecipitated with primate serum and resolved in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The expression of the Gal alpha(1,3)Gal epitope was analyzed on rat tissues and ECs by immunohistochemistry, flow cytometry, and Western blot, using the isolectin B4 from Griffonia simplicifolia. RESULTS: Removal of primate XNA or of alphaGal epitopes resulted in a decrease in XNA binding to pig and rat cells, leaving a similar degree of residual reactivity in the two species. At least five proteins of 260, 210, 110, 56, and 50 kDa were immunoprecipitated on rat ECs, with molecular weight similar to several proteins identified on pig ECs. These results suggest that primate XNA recognize similar antigens on rat and pig ECs. Rat cells expressed lower levels of the Gal alpha(1,3)Gal epitope than pig cells. A large proportion, but not all, of primate XNA react with this epitope on pig and rat ECs. CONCLUSION: This study suggests that the rat is a valuable species for the evaluation of genetic engineering strategies on the vascular endothelium aimed at preventing hyperacute xenograft rejection.

Animals↗
PubMed1991

Endogenous blockade of 1,25-dihydroxyvitamin D-receptor binding in New World primate cells.

When assessed by 1,25-dihydroxyvitamin D3 (1,25(OH)2-D3)-receptor (VDR) binding analysis or 1,25(OH)2-D3-VDR-directed bioresponsiveness, cultured cells from some New World primates (platyrrhines) demonstrate a variable decrement in VDR when compared with Old World primate (catarrhine) cells. To study this difference in VDR expression among primates, we performed immunoblot analysis of the VDR in cultured dermal fibroblasts from platyrrhines in the genera Pithecia and Aotus and from catarrhines in the genus Presbytis; although a platyrrhine, the owl monkey (Aotus) expresses a VDR of the catarrhine (wild type) phenotype. Despite a 10-fold difference in the content of VDR by ligand binding analysis among cells from the three prototypic primate genera, there was a less than or equal to 10% difference in the steady-state level of 50-kD VDR detected by immunoblot analysis of cellular extracts. We investigated this apparent discrepancy in the content of VDR in immunoblots and ligand binding analyses by mixing VDR-containing nuclear extracts of equivalent protein concentration from the various primates. Coincubation of Pithecia and Aotus fibroblast extracts with Presbytis extract diminished specific 1,25(OH)2-D3 binding in the mix by 90% and 95% respectively. Similar results were obtained by mixing nuclear extracts of the owl monkey cell line, OMK, and the vitamin D resistant marmoset B-lymphoblast cell line B95-8. A wild type 1,25(OH)2-D3-binding profile was restored in mixtures after trypsin or heat treatment of the B95-8 extract. These data indicate that some New World primate cells contain a soluble protein that prevents intracellular 1,25(OH)2-D3-VDR binding. It is possible that the quantitative differences in the expression of this protein are responsible for 1,25(OH)2-D3 and other steroid hormone resistant states of variable severity in New World primates.

Animals↗
PubMed1985

Diminished internalization and action of 1,25-dihydroxyvitamin D3 in dermal fibroblasts cultured from New World primates.

We investigated the occurrence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-resistant osteomalacia in the New World primate colony of Saguinus imperator at the Los Angeles Zoo. The mean serum concentration of 1,25-(OH)2D3 was elevated 5-fold in the New World primates compared to that in their Old World counterparts. The specific internalization of 0.6 nM [3H]1,25-(OH)2D3 by cultured dermal fibroblasts from New World primates was reduced 75% compared to that by cells from Old World primates or man. The decrease in hormone uptake resulted from a decrease in the number of high affinity intracellular binding sites for 1,25-(OH)2D3 and apparently caused a 90-95% reduction in 1,25-(OH)2D3-induced 25-hydroxyvitamin-D3-24-hydroxylase activity. There was no alteration in the capacity or avidity of New World primate serum for 1,25-(OH)2D3 compared to that of serum from Old World primates. These data suggest that the occurrence of vitamin D-resistant osteomalacia in New World primates is the result of decreased high affinity, receptor-mediated uptake of 1,25-(OH)2D3 by the target cell.

Animals↗