The role of pastoralism in regulating ecosystem services.

Pastoralism is rarely viewed as a major future form of land use, because of well-documented cases of rangeland degradation, attributed to irrational overstocking by pastoralists, and the subsequent losses of ecosystem services. However, pastoralists were actually encouraged to settle and adopt such strategies, copied from rangelands with higher and more reliable rainfall. This curtailed mobility resulted in a shift from opportunistic and extensive land use to more intensive and settled forms of use. The purpose of this review is to examine the link between pastoralism and the provision of ecosystem services by rangelands, focusing on biodiversity conservation and carbon sequestration. Pastoralists employ several techniques to manage rangeland resources, including mobility, herding, corralling, grazing reserves and the use of fire. With these strategies, pastoralists have contributed to the enhancement of rangeland biodiversity and the long-term conservation of important wildlife habitats. Pastoralists also possess detailed knowledge of rangeland plants and their uses, which could be valuable in the assessment, conservation and utilisation of rangeland biodiversity. Similarly, traditional pastoral rangeland management practices, such as the use of seasonal grassland reserves and livestock mobility, influence vegetation composition, coverage and abundance in rangelands and offer tools for biomass and soil carbon restoration, contributing to the mitigation of climate change. However, various internal and external factors have curtailed traditional management practices and livestock mobility, breaking the co-evolved balance of vegetation, wildlife and land use, thus exposing rangeland to continued livestock pressure, which often leads to degradation. Rather than abandoning pastoralism, the revitalisation of traditional practices and indigenous knowledge is vital to secure sustainable livelihoods for millions of pastoralists and to maintain rangeland biodiversity and ecosystem services.

Parmi les modalités d'utilisation des terres, le pastoralisme n'est guère considéré comme présentant un fort potentiel d'avenir, en raison d'exemples bien documentés de prairies dégradées suite à leur surexploitation irrationnelle par les pasteurs, entraînant une baisse des services écosystémiques qui leur étaient associés. Il faut toutefois rappeler que ces mêmes pasteurs avaient d'abord été encouragés à se sédentariser et à adopter ce type de stratégies, directement inspirées des pratiques d'élevage appliquées dans les prairies bénéficiant de précipitations plus importantes et plus fiables. Le déclin de la mobilité s'est traduit par le passage d'une utilisation opportuniste et extensive des terres à des formes d'exploitation plus intensives et sédentarisées. Les auteurs se sont attachés à faire apparaître les liens entre le pastoralisme et les services écosystémiques rendus par les prairies, en premier lieu la protection de la biodiversité et la séquestration de carbone. Les pasteurs recourent à diverses techniques pour gérer les ressources des prairies, dont la transhumance, la conduite des troupeaux, l'érection de clôtures, la rotation des pâtures et l'usage du feu. En déployant ces stratégies, les pasteurs ont contribué à améliorer la biodiversité des prairies et à assurer la conservation durable d'habitats importants pour la faune sauvage. Les pasteurs possèdent également une connaissance détaillée des espèces végétales poussant dans les prairies et de leur utilisation, qui s'avère précieuse pour évaluer, conserver et utiliser la biodiversité des prairies. De même, les pratiques pastorales traditionnelles de gestion des prairies telles que la rotation saisonnière des parcelles et les déplacements des troupeaux influent sur la répartition, la couverture et l'abondance de la végétation des prairies et constituent des outils permettant de réparer la biomasse et de séquestrer le carbone des sols, contribuant ainsi à atténuer le réchauffement climatique. Néanmoins, plusieurs facteurs internes et externes ont limité les pratiques de gestion traditionnelles et la mobilité des troupeaux, brisant l'équilibre d'une coévolution parallèle de la végétation, la faune sauvage et l'exploitation des terres, et exposant de ce fait les prairies à une pression permanente, souvent suivie de leur dégradation. Plutôt que de renoncer au pastoralisme, il est désormais crucial de revitaliser les pratiques traditionnelles et les savoirs autochtones afin de sécuriser les moyens de subsistance de millions de pasteurs et de préserver la biodiversité des prairies et les services écosystémiques.

Al pensar en las principales modalidades de usos del suelo de cara al futuro, rara vez se tiene en cuenta el pastoreo. Ello se debe a la existencia de casos probados de degradación de los pastos, atribuida a un acopio excesivo e irracional por parte de los pastores, y a la consiguiente pérdida de servicios ecosistémicos. La realidad, sin embargo, es que las comunidades de pastores fueron alentadas a asentarse y adoptar tales procederes, importados de zonas de pastizales con niveles más elevados y constantes de pluviosidad. La consiguiente limitación de la movilidad llevó a pasar de un uso oportunista y extensivo de las tierras a modalidades de explotación más intensivas y sedentarias. Los autores examinan aquí el vínculo entre el pastoreo y los servicios ecosistémicos ligados a los pastizales, centrándose sobre todo en la conservación de la diversidad biológica y el secuestro de carbono. Las sociedades de pastores emplean varias técnicas para gestionar los recursos que suponen las tierras de pasto, en particular la movilidad, el uso de rebaños, corrales y reservas de pastizales y el recurso al fuego. Con estas estrategias los pastores han contribuido a mejorar la diversidad biológica de los pastizales y a conservar duraderamente importantes hábitats de la fauna salvaje. Estas sociedades atesoran asimismo un detallado conocimiento de las plantas que forman los pastizales y de sus usos, lo que puede revestir gran utilidad para evaluar, preservar y utilizar la biodiversidad de los pastizales. Análogamente, las prácticas tradicionales de gestión de pastos que aplican los pastores (como el uso de reservas estacionales de tierras de pasto o la movilidad del ganado) influyen en la composición vegetal, la cobertura y la abundancia de los pastizales y brindan así herramientas para restaurar la biomasa y el carbono del suelo, ayudando con ello a mitigar el cambio climático. Sin embargo, hay una serie de factores internos y externos que han coartado las prácticas de gestión tradicionales y la movilidad del ganado, alterando el equilibrio entre vegetación, fauna salvaje y usos del suelo que se había alcanzado por coevolución y sometiendo así a los pastizales a una presión ganadera continua, que a menudo acaba por degradarlos. Más que de abandonar el pastoreo, se trata pues de revitalizar las prácticas tradicionales y el saber indígena como expediente crucial para procurar medios de sustento duraderos a los millones de personas que viven del pastoreo y a la vez mantener la diversidad biológica y los servicios ecosistémicos de los pastizales.

Methanococcus jannaschii ORF mj0608 codes for a class C inorganic pyrophosphatase protected by Co(2+) or Mn(2+) ions against fluoride inhibition.

Openreading frame mj0608 of the Methanococcus jannaschii genome, recognized by its sequence similarity to that of the gene coding for class C inorganic pyrophosphatase in Bacillus subtilis, was cloned and over-expressed in Escherichia coli. The protein was purified and characterized by SDS-PAGE, M(r), and N-terminal sequence. Under suitable conditions it catalyzed the specific hydrolysis of PPi at about 600 micromol x min(-1) x mg(-1) at 25 degrees C, and at 8000 micromol x min(-1) x mg(-1) at 85 degrees C. Therefore this protein is a specific inorganic pyrophosphatase. The activities of Mg(2+), Mn(2+), Co(2+), and Zn(2+) ions as cofactors for hydrolysis of PPi were compared at pH 7.5 and 9.0. Unlike the class C pyrophosphatase of B. subtilis, this enzyme required no prior activation by low concentrations of Mn(2+) or Co(2+) ions. However, prior exposure to these ions afforded striking protection against inhibition by sodium fluoride, to which the enzyme was otherwise very sensitive.

Purification, properties, and multiple forms of a manganese-activated inorganic pyrophosphatase from Bacillus subtilis.

The hydrolysis of magnesium pyrophosphate by inorganic pyrophosphatase from Bacillus subtilis required its specific, time-dependent, and prior activation by Mn2+ ions. This was reversed when Mn2+ ions were removed with EDTA. Free Mn2+ ions were not required for catalysis. Pyrophosphatase purified to near homogeneity gave a single main band of apparent M(r) 36,000 by SDS-PAGE, but of M(r) 34,000 by matrix-assisted laser desorption ionization-mass spectrometry. The native enzyme equilibrated at pH 7 between three distinct molecular forms. Exposure to Mn2+ generated a catalytically active trimer of specific activity about 5000 mumol pyrophosphate hydrolyzed/min/mg protein. Exposure to EDTA generated two catalytically inactive forms, a dimer at low ionic strength and a separate form, of uncharacterized multimeric nature, at molar concentrations of Na2SO4 or Li2SO4. The latter form was an intermediate in the dimer-trimer transition caused by addition or removal of manganese ions. Mn2+ reacted with this "intermediate" form, apparently by reversible association with two noninteracting binding sites of Kd approximately 0.005 and 0.35 microM, respectively. The properties of this enzyme may account in part for the unusual manganese requirements of B. subtilis and related species.

Purification of human hepatic arginase and its manganese (II)-dependent and pH-dependent interconversion between active and inactive forms: a possible pH-sensing function of the enzyme on the ornithine cycle.

Purification of human liver arginase by chromatography on DEAE-Sepharose, CM-Sepharose, hydroxylapatite, and MonoS yielded protein of greater than 95% purity by sodium dodecyl sulfate-gel electrophoresis. Detailed kinetic studies of the interconversion of active and inactive forms of arginase showed the effects of metal ion addition and withdrawal, metal ion type, time, temperature, and pH. At pH 7 and 37 degrees C, removal of Mn2+ caused a first-order deactivation with half-life of 1 h. Reactivation was completed within 0.5 min (1 mM Mn2+) or 90 min (ca. 6 nM Mn2+). Activation by Mn2+ showed a hyperbolic response, with Kd for Mn2+ of about 36 nM. Mn2+ apparently displaced about 2 H+, resulting in sigmoid dependence upon concentration of OH-. Both the maximal velocity of catalysis and the Km toward arginine were markedly pH-dependent in the physiological range. The findings lead to a model where Mn2+ allosterically activates arginase by a sequential, and pH-sensitive, mechanism. The combined pH sensitivities of activation, Vmax, and Km are likely to give arginase a role in mediating the demonstrated pH control of the ornithine cycle and hence in the regulation of body pH.

Cooperative manganese (II) activation of 3-phosphoglycerate mutase of Bacillus megaterium: a biological pH-sensing mechanism in bacterial spore formation and germination.

The conversion of 3-P-glycerate mutase of Bacillus megaterium from a catalytically inactive to an active form was markedly more effective with buffered Mn2+ than with just added Mn2+. The previously reported stimulation by threonine disappeared when buffered Mn2+ was used. Activation of mutase showed a sigmoid dependence on Mn2+ concentration when buffered with tetramethylenediamine tetraacetate. The curve obeyed Hill kinetics with a coefficient of 2.1 +/- 0.1. At 0.5 microM free Mn2+, buffered with trimethylenediamine tetraacetate, activation of mutase increased about 73-fold over the pH range 6.6 to 7.4. Plotted against [OH-], the activation showed a strongly sigmoid response with Hill coefficient of 3.5 +/- 0.1. When mutase activated at pH 6.4 and 0.5 microM free Mn2+ in the presence of substrate was transferred to a similar medium at pH 7.4, the rate of product accumulation increased 360-fold within a few minutes. The pH sensitivity conferred upon mutase by low [Mn2+] may account for its large activity decrease during sporulation, and later increase during spore germination, when spore pH, respectively, declines and rises by about 1 unit. These changes result in the accumulation, and later reutilization, of 3-P-glycerate reserves in the spore. Such a pH-sensing function of Mn2+ may have wider biological uses.

Manganese(II) activation of 3-phosphoglycerate mutase of Bacillus megaterium: pH-sensitive interconversion of active and inactive forms.

The effects of manganese(II) ions and of pH were studied on 3-p-glycerate mutase purified from Bacillus megaterium. Mn2+ ions converted the enzyme within a few minutes from a catalytically inactive form to one that was catalytically active even after Mn2+ had been removed. The enzyme reverted over 60-90 min to the inactive form, from which further activation-deactivation cycles could be elicited. The slow, temperature-dependent, activation, and deactivation is suggestive of change in protein conformation. No other metal ion was found that activated more than 4% as much as Mn2+. Activation by Mn2+ was strongly pH-dependent in the physiological pH range, consistent with displacement of 2 H+. Together with the pH dependence of the catalytic activity itself, the system displayed pronounced pH sensitivity in the pH range 6.5-8.0. The findings suggest that pH changes, documented for forming and germinating spores of B. megaterium, can account for much of the mutase control associated with accumulation and later utilization of 3-phosphoglycerate depots.

pH-sensitive control of arginase by Mn(II) ions at submicromolar concentrations.

The manganese dependence of arginase was reinvestigated with extracts of mouse liver to see whether more physiological properties were displayed than have been reported for the purified enzyme. In a preincubation with Mn(II) ions at 37 degrees C the enzyme underwent a slow and reversible activation. At least 90-95% of the activation achieved was dependent on Mn2+. However, no Mn2+ was required for catalytic activity in the assay. The activation showed little dependence upon pH over the range 6.5-9.5, whereas the catalytic activity increased 12-fold in apparent accord with the titration curve of an ionizable group of pKa 7.9. The Mn2+ dependence of arginase activation obeyed Michaelis-Menten kinetics, with Kd varying from 0.3 microM at pH 6.8 to 0.08 microns at pH 7.7. Free Mn2+ concentrations were established in these assays with a trimethylenediaminetetraacetate-Mn buffer. Vmax increased about three-fold over this range. The calculated arginase activity at 0.05 microM Mn2+ increases about nine-fold over this physiological pH range. An enzyme model is proposed to explain these findings. The activity of arginase at "physiological" [Mn2+] and the pronounced pH dependence conferred upon it are consistent with a recently revised role for the urea cycle in the control of bicarbonate and pH in the body. It appears possible that arginase loses Mn2+ sensitivity during the usual purification.

Submicromolar manganese dependence of Golgi vesicular galactosyltransferase (lactose synthetase).

1. Manganese(II) buffers were set up with inorganic triphosphate, trimethylenediaminetetraacetate and tetramethylenediaminetetraacetate to study the Mn dependence of beta 1,4-galactosyltransferase (lactose synthetase) in preparations of rat mammary gland. 2. In intact particulate preparations, treated with the calcium ionophore A23187, lactose synthesis was abolished by chelators and restored by bivalent transition metal ions in a manner characteristic of activation site I of the pure enzyme. Ni(II) also activated, as did Mg at high concentration. 3. Only Mn(II) could restore endogenous rates, giving an apparent Km of 0.1-0.2 microM, and eliciting about 70% full activity without addition of a site II activator. 4. In purified Golgi membrane vesicles, Mn gave an apparent Km of 0.4 microM. This increased sharply to about 10 microM on permeabilization with filipin, lysis with detergents, solubilization with Triton X-100, or in the pure enzyme. Preparations of chemically undamaged Golgi vesicles, known to include a proportion of the enzyme on exposed membranes, exhibited both low-Km and high-Km components. 5. The response of particulate galactosyltransferase to apparently physiological concentrations of free Mn(II) ion is interpreted as either due to a sensitizing factor within the Golgi lumen, or to the accumulation of Mn at elevated concentrations. Alternatively, the high Km of the soluble enzyme may reflect proteolytic damage.

T antigen expression and tumorigenesis in transgenic mice containing a mouse major urinary protein/SV40 T antigen hybrid gene.

A hybrid mouse major urinary protein (MUP)/SV40 T antigen gene was microinjected into fertilized mouse embryos and the resulting transgenic mice analyzed for the regulated expression of the transgene. Available evidence indicates that the MUP gene used for the hybrid gene construct is expressed in both male and female liver and possibly mammary gland. Three different transgenic lines exhibited a consistent pattern of tissue specific expression of the transgene. As a consequence of transgene expression and T antigen synthesis in the liver, both male and female transgenic animals developed liver hyperplasia and tumors. Transgene expression and liver hyperplasia commenced at approximately 2-4 weeks of age, the same time that MUP gene expression is first detected in the liver. The expression of the transgene resulted in an immediate strong suppression of liver MUP mRNA levels but had relatively little effect on other liver specific mRNAs. From 4 to 8 weeks, the liver increased several fold in size, relative to non-transgenic littermates. Definitive tumor nodules were not apparent until 8-10 weeks. The transgene was also consistently found to be expressed in the skin sebaceous glands and the preputial gland, a modified sebaceous gland. The expression of the transgene in the skin sebaceous glands is consistent with the presence of MUP mRNA in the skin and a putative role for MUPs in the transport and excretion of small molecules. Occasional expression of the transgene in other tissues (kidney and mammary connective tissues) was also noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Purification, properties and cation activation of galactosyltransferase from lactating-rat mammary Golgi membranes.

Galactosyltransferase was purified from Golgi membranes of lactating-rat mammary gland and studied with respect to its physical and enzymic (lactose synthetase) properties. The enzyme occurred in both monomeric (43-46 kDa) and apparently dimeric (90 kDa) forms. It was very unstable except in the presence of phospholipid, detergent, or cations binding to site 2. The amino acid composition and the N-terminal sequence closely resembled that of the human and bovine milk enzymes, particularly in respect to a Pro-Pro-Pro-Pro sequence. Kinetic studies demonstrated a high-affinity Mn2+-binding site (1) essential for activity, and a low-affinity Mn2+-binding site (2) that could also bind spermidine or clupeine. Mn2+ binding at site 2 raised Vmax fivefold. Spermidine binding at site 2 enhanced Mn2+ binding at site 1, and influenced binding of glucose. At physiological glucose concentration, clupeine or spermidine activated nearly as well as 15 mM MnCl2 and are regarded as models of a natural cation activator that remains to be isolated. Evidence is given for an essential histidine residue in the galactosyltransferase. It is proposed that site 1 Mn2+ participates directly in the reaction mechanism, whereas site 2 is a regulator site allosterically activated by a basic protein.

Identification and characterization of functional genes encoding the mouse major urinary proteins.

Mouse Ltk- cells were stably transfected with cloned genes encoding the mouse major urinary proteins (MUPs). C57BL/6J MUP genomic clones encoding MUP 2 (BL6-25 and BL6-51), MUP 3 (BL6-11 and BL6-3), and MUP 4 (BL6-42) have been identified. In C57BL/6J mice, MUP 2 and MUP 4 are known to be synthesized in male, but not female, liver, and MUP 3 is known to be synthesized in both male and female liver and mammary gland. A BALB/c genomic clone (BJ-31) was shown to encode a MUP that is slightly more basic than MUP 2 and was previously shown to be synthesized in both male and female liver of BALB/c but not C57BL/6 mice. Comigration on two-dimensional polyacrylamide gels of the MUPs encoded by the transfecting gene provides a basis for tentative identification of the tissue specificity and mode of regulation of each gene. DNA sequence analysis of the 5' flanking region indicates that the different MUP genes are highly homologous (0.20 to 2.40% divergence) within the 879 base pairs analyzed. The most prominent differences in sequence occur within an A-rich region just 5' of the TATA box. This region (from -47 to -93) contains primarily A or C(A)N nucleotides and varies from 15 to 46 nucleotides in length in the different clones.

Arteriovenous glucose differences across the mammary gland of the fed, starved, and re-fed lactating rat.

Arteriovenous glucose difference across the mammary gland of the lactating rat was used as an 'instantaneous' monitor of mammary glucose uptake. Plasma [glucose] and arteriovenous glucose difference varied according to whether Halothane, diethyl ether or sodium pentobarbitone anaesthesia was used. In pentobarbitone-treated rats a 60% glucose extraction in the fed state decreased to 5% after 18 h starvation, and recovered to 40% and 59% after 15 min and 60 min re-feeding respectively. The increase and decrease in plasma [fatty acids] and the depletion and restoration of hepatic glycogen mostly followed similar time courses. Re-feeding was accompanied by a brief surge of plasma [insulin]. Starved lactating rats showed a markedly greater capacity than age-matched virgin rats in the oral and intraperitoneal glucose tolerance tests. Mammary glucose uptake in the starved rat was significantly restored by oral or intraperitoneal glucose or by insulin, but not by acetoacetate or by heparin-induced elevation of plasma [fatty acids]. The role of insulin and of possible changes in mammary sensitivity to insulin in the return of mammary glucose uptake on re-feeding is discussed.

Cationic activation of galactosyltransferase from rat mammary Golgi membranes by polyamines and by basic peptides and proteins.

Galactosyltransferase (EC 2.4.1.22) requires bivalent metal ions for its activity. However, preparations of this enzyme solubilized from Golgi membranes of lactating rat mammary gland were shown to be activated not only by Mn2+, Ca2+ and Mg2+, but also by spermine, spermidine, lysyl-lysine, ethylenediamine and other diaminoalkanes, and by a range of basic proteins and peptides, including clupeine, histone, polylysine, ribonuclease, pancreatic trypsin inhibitor, cytochrome c, melittin, avidin and myelin basic protein. Both N-acetyl-lactosamine synthetase and lactose synthetase activities were enhanced. A basic protein fraction was isolated from bovine milk and shown to activate galactosyltransferase at low concentrations. The polyanions ATP, casein, chondroitin sulphate and heparin reversed the activation of galactosyltransferase by several of the above substances. Galactosyltransferase, assayed as a lactose synthetase, showed a 10-fold greater affinity for glucose when Mn2+ ions were replaced by clupeine or by ribonuclease as cationic activator. Evidence was obtained for the presence of an endogenous cationic activator in solubilized Golgi membrane preparations which evoked a similar low apparent Km,glucose. The findings are discussed in the light of cationic activations of glycosyltransferases generally, of the porous nature of the Golgi membrane, and of the unlikelihood of bivalent metal ions being the physiological activators of galactosyltransferase. It is suggested that the natural cationic activator of lactose synthetase may be a secretory protein acting in a manner analogous to the enzyme's activation by alpha-lactalbumin. A scheme is proposed for the two-stage synthesis of lactose and phosphorylation of casein within the cell, to accommodate the apparent incompatibility of these two processes.

Incorporation into phospholipid vesicles of pore-like properties from Golgi membranes of lactating-rat mammary gland.

The ability of rat mammary-gland Golgi membranes to produce monosaccharide-specific pores in phospholipid vesicles was investigated. The apparent ability of Triton X-100 extracts of Golgi membranes to form such pores was re-evaluated, since we have now found that an apparent pore is produced by the detergent alone. We therefore incorporated intact Golgi membranes (1 mg of protein) into egg-yolk phospholipid vesicles by direct sonication in the absence of any detergent. These vesicles retained about 0.6% of the total sucrose, but demonstrated selective permeability towards glucose compared with sucrose, with 19.8% of the glucose being lost during gel filtration on Sepharose 4B. This phenomenon seemed to be enhanced by the presence of acidic phospholipids and lysophosphatidylcholine, but was inhibited by inclusion of cholesterol in the vesicles. The best mixture of phospholipids comprised 6.5 mg of egg-yolk phospholipid, 1 mg of phosphatidylserine and 0.05 mg of lysophosphatidylcholine, where 32.9% of the glucose was lost. By using this optimum phospholipid mixture the pores were shown to be permeable to both glucose and mannitol, whereas sucrose and lactose were retained by the vesicles. Chaps (3- [(3-cholamidopropyl)dimethylammonio] propane-1-sulphonate)-solubilized membranes produced similar permeability in vesicles produced by dialysis of a solution of the phospholipids mixed with the membrane extract. This technique resulted in a greater loss of glucose, 33% loss requiring about 0.25 mg of protein. The pore-forming ability of both intact Golgi membranes and Chaps extracts was sensitive to boiling and proteolysis, indicating that a membrane protein was likely to be involved in pore formation.

Role of fructose 2,6-bisphosphate in mammary gland of fed, starved and re-fed lactating rats.

The fructose 2,6-bisphosphate (Fru-2,6-P2) content and intracellular concentration of lactating mammary gland was measured in fed, starved and re-fed rats. There was little or no change on starvation, and about 1.5-fold rise on re-feeding, contrasting with estimated glycolytic changes of about 10-fold. The 6-phosphofructokinase (PFK-1) activity of mammary extracts was highly sensitive to added Fru-2,6-P2 under all conditions examined, and appeared to approach saturation at physiological concentrations of this effector. The activity of mammary PFK-1 measured under optimal and 'physiological' conditions suggested that this enzyme operates in vivo at about 24% of maximal rate, and is likely to be an important rate-limiting factor in mammary glycolysis.

Subfamilies of the mouse major urinary protein (MUP) multi-gene family: sequence analysis of cDNA clones and differential regulation in the liver.

The mouse major urinary proteins (MUPs) are the products of a multi-gene family of 30-35 genes whose members exhibit diverse tissue specific, developmental, and hormonal controls. Three cDNA clones corresponding to liver MUP mRNAs have been sequenced. Two of the clones (p499, C57BL/6 and p1057, BALB/c) share strong homology whereas a third clone (p199, C57BL/6) has diverged considerably from the others at the nucleic acid (85% homology) and protein (68% homology) levels. The 5' regions of p499 and p199 which show the most sequence divergence were subcloned and shown to hybridize to different liver MUP mRNAs. The p499-5' sequence was expressed in all MUP expressing tissues (liver, lachrymal, submaxillary and mammary) whereas the p199-5' sequence was expressed primarily in the liver and lachrymal. Analysis of liver RNA from mice in different endocrine states indicates that the p499-5' sequence is strongly regulated by thyroxine administration whereas the p199-5' sequence is not. Both sequences appear to be regulated by growth hormone and testosterone. Southern blot analysis of mouse genomic DNA indicates that there are multiple genes homologous to each sequence.