Chromatographic Separation of Puberty Accelerating Pheromone from Male Mouse Urine1

Vandenbergh, John G.; Finlayson, J. S.; Dobrogosz, Walter J.; Dills, S S; Kost, Thomas A.

doi:10.1095/biolreprod15.2.260

Cited by 96 publications

(33 citation statements)

References 15 publications

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“…Secondly, the pheromone is a low molecular weight substance, not necessarily a peptide, that is bound with the peptide fraction. It is interesting that the male pheromone responsible for accelerated maturation of female mice is also present in a urinary peptide fraction (Vandenbergh et al 1976). …”

Section: Discussionmentioning

confidence: 99%

“…It is well documented that the production and release of these biologically active substances are under androgenic control (Dominic, 1965;Bronson & Whitten, 1968;Vandenbergh, 1969) but the chemical nature of the olfactory stimulants is still unknown. A urinary fraction containing peptides and a peak molecular weight of 860 has been shown to have activity (Vandenbergh, Whitsett & Lombardi, 1975;Vandenbergh, Finlayson, Dobrogosz, Dills & Kost, 1976).…”

Section: Introductionmentioning

confidence: 99%

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Pregnancy block elicited by male urinary peptides in mice

Marchlewska-Koj¹

1981

Reproduction

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pregnancy block elicited by male urinary peptides in mice

Marchlewska-Koj¹

1981

Reproduction

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“…It is not well understood how these neurons encode information about gender and individuals. Urine contains hundreds or even thousands of substances, only a handful of which have been identified as putative pheromones (12)(13)(14)(15)(16). The complexity of natural pheromone signals poses a challenge to our understanding of what information is transmitted to the vomeronasal neurons (17,18).…”

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confidence: 99%

Encoding Gender and Individual Information in the Mouse Vomeronasal Organ

Kim

et al. 2008

Science

162

160

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The mammalian vomeronasal organ detects complex chemical signals that convey information about gender, strain, and the social and reproductive status of an individual. How these signals are encoded is poorly understood. We developed transgenic mice expressing the calcium indicator G-CaMP2 and analyzed population responses of vomeronasal neurons to urine from individual animals. A substantial portion of cells was activated by either male or female urine, but only a small population of cells responded exclusively to gender-specific cues shared across strains and individuals. Female cues activated more cells and were subject to more complex hormonal regulations than male cues. In contrast to gender, strain and individual information was encoded by the combinatorial activation of neurons such that urine from different individuals activated distinctive cell populations.Pheromones are a group of chemicals critical for social communication in many animal species (1,2). Information on sex, strain, social rank, reproductive status, and terrestrial ownership is represented in the complex pheromone components in urine and bodily secretions. In mice, detection of such complex chemical signals by the vomeronasal organ (VNO) and the olfactory epithelium plays an important role in triggering endocrine changes and eliciting innate territorial aggression and mating behaviors (3-5). The rodent VNO expresses more than 250 receptors that detect pheromones and transmit the signals to the brain (6-11). It is not well understood how these neurons encode information about gender and individuals. Urine contains hundreds or even thousands of substances, only a handful of which have been identified as putative pheromones (12-16). The complexity of natural pheromone signals poses a challenge to our understanding of what information is transmitted to the vomeronasal neurons (17,18).Each vomeronasal neuron expresses only one of the ∼250 estimated pheromone receptor genes (6)(7)(8)(9)19,20), and the receptor's activation elevates intracellular calcium (21). To visualize pheromone-induced activity in a large population of neurons, we generated tetO-G-CaMP2 transgenic mouse lines (22)(23)(24). When crossed to animals carrying the OMP-IRES-tTA allele (25), G-CaMP2 expression was restricted to the neurons in the olfactory system (Fig. 1, A and B, and Movie S1). Electrophysiological properties of the G-CaMP2-expressing VNO neurons, as well as their response to pheromones, were indistinguishable from those of the controls ( fig. S1). The projection patterns of the sensory neurons and the innate mating and aggressive behaviors of the G-CaMP2 mice were also indistinguishable from those of wild-type and littermate control animals (figs. S2 to S5). In VNO slices prepared from 2-to 6-month-old male or female animals, application of diluted urine elicited an increase in fluorescence in ∼30 to 40% of G-CaMP2-positive neurons, some of which showed gender-specific responses ( Fig. 1C and Movies S2 and S3). We did not observe significant differences...

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“…The physiological role of these proteins is not known. Because of the coincidence in timing of the appearance of MUPs in the liver and the onset of puberty, the possibility that MUPs participate in the sexual development of mice has been suggested (26). Re-cently it was observed that mRNAs related to liver MUP mRNA are also present in the submaxillary, sublingual, parotid, lachrymal, and mammary glands (21).…”

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Tissue-specific expression of major urinary protein (MUP) genes in mice: characterization of MUP mRNAs by restriction mapping of cDNA and by in vitro translation.

Shahan¹,

Derman²

1984

Mol. Cell. Biol.

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The major urinary proteins (MUPs) in mice are coded for by a gene family which consists of ca. 30 members. The number of MUP genes that are expressed is not known. Previous studies have shown that MUP mRNAs are present in several secretory tissues in addition to the liver, in which they were originally identified. In this paper we show, through restriction analysis of MUP cDNAs, that distinct sets of MUP mRNAs are synthesized in each of the tissues studied and that these mRNAs are most likely coded for by different genes. As is shown, MUP mRNAs of different tissues are related to an extent that precludes the use of gene-specific probes in differentiating among them. The regions of homology also include the 3' untranslated regions of MUP mRNAs. The question of differential expression was thus investigated by searching for restriction polymorphisms in MUP mRNAs. We demonstrate that subtle differences in the sequences of even scarce mRNAs can be recognized by this particular approach. In addition, it is shown that MUP mRNAs of different tissues code for different, nonoverlapping sets of polypeptides, as determined by gel electrophoresis of in vitro-translated precursors to MUPs. The relevance of these results to models of evolution of tissue-specific regulation in a multigene family is discussed.It appears that the synthesis of tissue-specific mRNAs at the appropriate stage of development is controlled through transcriptional regulation (8, 9). The mechanisms of this regulation are not known, nor is it known how this type of regulation arose during evolution. As has been suggested (see, e.g., reference 12), detailed studies of the structure of tissue-specific genes which belong to multigene families should provide clues concerning both the evolution and the molecular basis of tissue-specific regulation. In this paper we show that the genes coding for major urinary proteins (MUPs) form such a gene family.MUPs were originally recognized because of their high concentration in the urine of adult male mice. The urinary MUPs are synthesized in the liver (13,23) under the influence of a number of hormones, including thyroxine, growth hormone, and testosterone (16,21 The MUPs are coded for by ca. 30 genes that are clustered in the Mup-a locus of chromosome 4 (1, 5). Because of the presence of a large number of MUP genes, the possibility exists that MUP genes are differentially expressed in different tissues. This question was thus investigated with the focus on expression of MUP genes in the liver and the submaxillary, sublingual, and lachrymal glands. MATERIALS AND METHODSAnimals. An inbred strain of Swiss white mice (NCS) raised at The Rockefeller University was used in all experiments.Preparation of poly(A+) RNA. Polyadenylated [poly(A+)] RNA was extracted from fresh mouse tissues by the technique of Chirgwin et al. (4) as previously described (9).RNA electrophoresis and blotting. The procedures used were those of D. Goldberg and B. Seed (unpublished) and Thomas (25). Poly(A+) RNA was denatured by heating for 5 min at ...

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Chromatographic Separation of Puberty Accelerating Pheromone from Male Mouse Urine1

Cited by 96 publications

References 15 publications

Pregnancy block elicited by male urinary peptides in mice

Pregnancy block elicited by male urinary peptides in mice

Encoding Gender and Individual Information in the Mouse Vomeronasal Organ

Tissue-specific expression of major urinary protein (MUP) genes in mice: characterization of MUP mRNAs by restriction mapping of cDNA and by in vitro translation.

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