An ultraviolet-optical flare from the tidal disruption of a helium-rich stellar core.

The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two 'relativistic' candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report a luminous ultraviolet-optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.

In vitro method to evaluate virus competition between BVDV-1 and BVDV-2 strains using the PrimeFlow RNA assay.

Bovine viral diarrhea viruses (BVDV), segregated in BVDV-1 and BVDV-2 species, lead to substantial economic losses to the cattle industry worldwide. It has been hypothesized that there could be differences in level of replication, pathogenesis and tissue tropism between BVDV-1 and BVDV-2 strains. Thus, this study developed an in vitro method to evaluate virus competition between BVDV-1 and BVDV-2 strains. To this end the competitive dynamics of BVDV-1a, BVDV-1b, and BVDV-2a strains in cell cultures was evaluated by a PrimeFlow RNA assay. Similar results were observed in this study, as was observed in an earlier in vivo transmission study. Competitive exclusion was observed as the BVDV-2a strains dominated and excluded the BVDV-1a and BVDV-1b strains. The in vitro model developed can be used to identify viral variations that result in differences in frequency of subgenotypes detected in the field, vaccine failure, pathogenesis, and strain dependent variation in immune responses.

Bovine viral diarrhoea virus infection alters global transcription profiles in bovine endothelial cells.

Bovine viral diarrhoea viruses (BVDV) are significant pathogens of cattle worldwide. These viruses exist in both non-cytopathic and cytopathic biotypes. Non-cytopathic BVDV can establish persistent lifelong infections in cattle and are a frequent contaminant of biological reagents such as cell cultures and foetal bovine serum. We identified commercially available bovine aortic endothelial cells (BAECs) contaminated with BVDV. In this study, to determine if BVDV alters endothelial gene transcription patterns, serial analysis of gene expression (SAGE) was used to compare gene expression profiles from uninfected and BVDV contaminated BAEC. SAGE is an open ended, quantitative method for characterizing global patterns of transcription. Comparison of expression profiles of BVDV-contaminated and noninfected cells revealed significant increases in the transcription of many genes including P-selectin, tryptophan tRNA synthetase and prostaglandin D2 synthase. These changes were validated by real-time PCR. Additionally, real-time PCR demonstrated that the response to LPS and dsRNA by contaminated cells, as well as cells acutely infected with noncytopathic BVDV, is altered. The altered response may be through the high level of expression of A20 and inhibition of activation of NF-kappaB. BAECs are commonly used as a model to study endothelial cell function in many different systems. As shown here, transcriptional and probable protein changes resulting from BVDV infection significantly alter cellular responses and may have a profound impact on experimental outcome. Transcriptomic analysis provided the initial clues leading to the characterization of this altered function.

Effect of porcine reproductive and respiratory syndrome virus on porcine alveolar macrophage function as determined using serial analysis of gene expression (SAGE).

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide and causes considerable economic loss. The main target of infection is the porcine alveolar macrophage (PAM). Infection of PAMs by PRRSV causes significant changes in their function by mechanisms that are not understood. We have employed Serial Analysis of Gene Expression (SAGE) to examine the global expression of genes in PRRSV-infected PAMs. Total cellular RNAwas prepared from in vitro mock-infected and PRRSV strain VR-2332-infected PAMs at 0, 6, 12, 16 and 24 hours after infection, and subjected to SAGE analysis to obtain > 100,000 tags per time point. These sequences were processed to account for sequencing error before generating tag:count lists. These lists were deposited into a modified Identitag database for mapping to porcine and PRRSV genes. Identified unique mRNAtags were analyzed for their identity and relative abundance. Examination of the SAGE data indicated that there were changes in gene expression occurring in the PRRSV-infected PAMs over time post-infection. More than 400 unique tags with significantly altered expression levels were identified (p < 0.01 with Bonferroni correction). The validity and kinetics of expression of SAGE identified genes were evaluated using real-time RT-PCR.

Serological survey for antibodies against pestiviruses in Wyoming domestic sheep.

Pestiviruses including Bovine viral diarrhea virus type 1 (BVDV-1), BVDV-2 and Border disease virus (BDV) have been reported in both sheep and cattle populations, together with the HoBi-like, an emerging group of pestiviruses. Pestivirus control programs in the United States have focused on the control of BVDV-1 and 2. The incidence of pestivirus infection in sheep in the United States and the risk of transmission between cattle and sheep populations are unknown. The aim of this study was to perform serological surveillance for pestivirus exposure in sheep from an important sheep producing state in the Unites States, Wyoming. For this, sera from 500 sheep, collected across the state of Wyoming (US) in 2015-2016, were examined by comparative virus neutralization assay against four species/proposed species of pestiviruses: BVDV-1, BVDV-2, BDV and HoBi-like virus. Rates of exposure varied between geographic regions within the state. The overall pestivirus prevalence of antibodies was 5.6%. Antibodies were most frequently detected against BVDV-1 (4%), and the highest antibody titers were also against BVDV-1. Data from this study highlights understanding of the dynamics of sheep pestivirus exposure, consideration of reference strains used for VN assays, transmission patterns, and potential vaccination history should be taken into account in implementation of control measures against pestiviruses in sheep and for successful BVDV control programs in cattle.

Activation of cell signaling pathways is dependant on the biotype of bovine viral diarrhea viruses type 2.

Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Besides the segregation into two distinct species (BVDV1/BVDV2) two different biotypes, a cytopathic (cp) and a noncytopathic (ncp) biotype, are distinguished based on their behavior in epithelial cell cultures. One of the most serious forms of BVDV infection affecting immunocompetent animals of all ages is severe acute BVD (sa BVD) which is caused by highly virulent ncp BVDV2 strains. Previous studies revealed that these highly virulent ncp viruses cause cell death in a lymphoid cell line (BL3) which is not clearly associated with typical apoptotic changes (e.g. PARP cleavage) observed after infection with cp BVDV. To further characterize the underlying molecular mechanisms, we first analyzed the role of the mitochondria and caspases as key mediators of apoptosis. Compared to infection with cp BVDV2, infection with highly virulent ncp BVDV2 resulted in a delayed and less pronounced disruption of the mitochondrial transmembrane potential (DeltaPsi(m)) and a weaker activation of the caspase cascade. In contrast, infection with low virulence ncp BVDV2 showed no significant differences from the uninfected control cells. Since different pro- and anti-apoptotic cellular signaling pathways may become activated upon virus infection, we compared the effect of different BVDV2 strains on cellular signaling pathways in BL3 cells. Stress-mediated p38 MAPK phosphorylation was detected only in cells infected with cp BVDV2. Interestingly, infection with highly virulent ncp BVDV2 was found to influence the phosphoinositide 3-kinase (PI3K)-Akt pathway. This indicates that BL3 cells respond differently to infection with BVDV depending on virulence and biotype.

Genomic and antigenic characterization of bovine parainfluenza-3 viruses in the United States including modified live virus vaccine (MLV) strains and field strains from cattle.

This study investigated the genetic and antigenic characterization of parainfluenza-3 virus (PI3V) of cattle. Using molecular tests including real time PCR and viral genome sequencing, PI3V strains could be separated into PI3V types, including PI3V A, PI3V B, and PI3V C. Isolates from cattle with bovine respiratory disease clinical signs and commercial vaccines in the U.S. with MLV PI3V were typed using these molecular tests. All the MLV vaccine strains tested were PI3V A. In most cases PI3V field strains from calves receiving MLV vaccines were types heterologous to the vaccine type A. Also antigenic differences were noted as PI3V C strains had lower antibody levels than PI3V A in serums from cattle receiving MLV PI3V A vaccines. This study further demonstrates there is genetic variability of U.S. PI3V strains and also antigenic variability. In addition, isolates from cattle with BRD signs and receiving MLV vaccines may have heterologous types to the vaccines, and molecular tests should be performed to differentiate field from vaccine strains. Potentially the efficacy of current PI3V A vaccines should be evaluated with other types such a PI3V B and PI3V C.

iPTF16geu: A multiply imaged, gravitationally lensed type Ia supernova.

We report the discovery of a multiply imaged, gravitationally lensed type Ia supernova, iPTF16geu (SN 2016geu), at redshift z = 0.409. This phenomenon was identified because the light from the stellar explosion was magnified more than 50 times by the curvature of space around matter in an intervening galaxy. We used high-spatial-resolution observations to resolve four images of the lensed supernova, approximately 0.3 arc seconds from the center of the foreground galaxy. The observations probe a physical scale of ~1 kiloparsec, smaller than is typical in other studies of extragalactic gravitational lensing. The large magnification and symmetric image configuration imply close alignment between the lines of sight to the supernova and to the lens. The relative magnifications of the four images provide evidence for substructures in the lensing galaxy.

Detection of viruses: atomic force microscopy and surface enhanced Raman spectroscopy.

This paper demonstrates the capability of atomic force microscopy (AFM) and surface enhanced Raman spectroscopy (SERS) to function effectively as ultra-sensitive readout tools for chip-scale platforms designed for pathogen detection in complex biological media. AFM allows direct (i.e., label-free) visualization and quantification of nanometer-sized viruses captured on a smooth, selective surface. AFM readout led to optimization of a capture substrate for feline calicivirus (FCV), and yielded a limit of detection of 3 x 10(6) FCV/mL. SERS-based detection of FCV, carried out in a sandwich-type assay, requires labelling of the substrate-bound FCV with a selective extrinsic Raman label (ERL). These studies yielded a limit of detection of 1 x 10(6) FCV/mL. The prospects of these two readout methods as additions to the arsenal of tools in bioterrorism prevention are briefly discussed.

Expression of the messenger RNAs for luteinizing hormone-releasing hormone (LHRH) and its receptor in human ovarian epithelial carcinoma.

Recently we reported the presence of specific high affinity binding sites for luteinizing hormone-releasing hormone (LHRH) and its analogues (Kd = 1.5 or 1.7 nM) in the human epithelial ovarian cancer cell lines EFO-21 and EFO-27. The proliferation of these cell lines was inhibited by nM concentrations of a LHRH agonist. This study was performed to ascertain whether these ovarian cancer cell lines produce LHRH and whether the high affinity LHRH binding site found previously was identical to the pituitary LHRH receptor. Significant amounts of immunoreactive LHRH were found in the extracts of both the EFO-21 cell line (449 +/- 56 fmol/10(6) cells) and the EFO-27 line (409 +/- 76 fmol/10(6) cells). LHRH bioactivity of these extracts, assessed in terms of release of luteinizing hormone by rat pituitary cells, was comparable to that of authentic LHRH. EFO-21 and EFO-27 cells expressed the mRNAs for both human LHRH and human LHRH receptor as assessed by reverse transcriptase-PCR using oligonucleotide primers according to published sequences. In addition, in eight of eight biopsy samples of human epithelial ovarian cancers we detected mRNA for LHRH, six of these specimens expressed the mRNA representing the LHRH receptor. These data support the concept that human epithelial ovarian cancers might have a local system based on LHRH to regulate cell proliferation. It is still obscure at present whether LHRH produced locally has a stimulatory, inhibitory, or no impact on the proliferation of ovarian cancer cells. However, exogenous LHRH agonists seem to have clear antiproliferative activity, probably mediated through LHRH receptors. This finding might provide the base for novel approaches in the therapy of epithelial ovarian cancer.

Comparison of 'HoBi'-like viral populations among persistent infected calves generated under experimental conditions and to inoculum virus.

Like other members from the Pestivirus genus, 'HoBi'-like pestiviruses cause economic losses for cattle producers due to both acute and persistent infections. The present study analyzed for the first time PI animals derived from a controlled infection with two different 'HoBi'-like strains where the animals were maintained under conditions where superinfection by other pestiviruses could be excluded. The sequence of the region coding for viral glycoproteins E1/E2 of variants within the swarms of viruses present in the PI calves and two viral inoculums used to generate them were compared. Differences in genetic composition of the viral swarms were observed suggesting that host factors can play a role in genetic variations among PIs. Moreover, PIs generated with the same inoculum showed amino acid substitutions in similar sites of the polyprotein, even in serum from PIs with different quasispecies composition, reinforcing that some specific sites in E2 are important for host adaptation.

Detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease.

This study investigated viruses in bovine respiratory disease (BRD) cases in feedlots, including bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronaviruses (BoCV) and parainfluenza-3 virus (PI3V). Nasal swabs were collected from 114 cattle on initial BRD treatment. Processing included modified live virus (MLV) vaccination. Seven BRD necropsy cases were included for 121 total cases. Mean number of days on feed before first sample was 14.9 days. Swabs and tissue homogenates were tested by gel based PCR (G-PCR), quantitative-PCR (qPCR) and quantitative real time reverse transcriptase PCR (qRT-PCR) and viral culture. There were 87/114 (76.3%) swabs positive for at least one virus by at least one test. All necropsy cases were positive for at least one virus. Of 121 cases, positives included 18/121 (14.9%) BoHV-1; 19/121 (15.7%) BVDV; 76/121 (62.8%) BoCV; 11/121 (9.1%) BRSV; and 10/121 (8.3%) PI3V. For nasal swabs, G-PCR (5 viruses) detected 44/114 (38.6%); q-PCR and qRT-PCR (4 viruses) detected 81/114 (71.6%); and virus isolation detected 40/114 (35.1%). Most were positive for only one or two tests, but not all three tests. Necropsy cases had positives: 5/7 G-PCR, 5/7 q-PCR and qRT-PCR, and all were positive by cell culture. In some cases, G-PCR and both real time PCR were negative for BoHV-1, BVDV, and PI3V in samples positive by culture. PCR did not differentiate field from vaccines strains of BoHV-1, BVDV, and PI3V. However based on sequencing and analysis, field and vaccine strains of culture positive BoHV-1, BoCV, BVDV, and PI3V, 11/18 (61.1%) of BoHV-1 isolates, 6/17 (35.3%) BVDV isolates, and 1/10 (10.0%) PI3V identified as vaccine. BRSV was only identified by PCR testing. Interpretation of laboratory tests is appropriate as molecular based tests and virus isolation cannot separate field from vaccine strains. Additional testing using sequencing appears appropriate for identifying vaccine strains.

Isolation and characterization of interleukin-1 from bovine polymorphonuclear leukocytes.

Interleukin-1 (IL-1 alpha and IL-1 beta collectively) has been shown to be produced by a wide variety of cell types. The purpose of this study was to evaluate the ability of bovine polymorphonuclear leukocytes (PMNs) to synthesize and release IL-1-like cytokines and characterize the active molecule(s). Purified peripheral blood PMNs were cultured for various periods of time in the presence of opsonized zymosan particles. The resulting culture supernatants exhibited IL-1 activity as determined by enhanced mitogen-induced proliferation of the D10 G4.1 murine T-helper cell line. Supernatants from nonstimulated PMNs or PMNs stimulated for less than 6 h did not enhance D10 G4.1 proliferation. The active molecule (PMNIL-1) was isolated by using gel filtration high-performance liquid chromatography (HPLC). Further characterization of the HPLC-purified molecule by SDS-PAGE and isoelectric focusing indicates bovine PMNIL-1 has a molecular weight of 17.8 kd and a pI of 4.1.

Comparison of the breadth and complexity of bovine viral diarrhea (BVDV) populations circulating in 34 persistently infected cattle generated in one outbreak.

Exposure to bovine viral diarrhea viruses (BVDV) results in acute and persistent infections. Persistent infections result from in utero exposure during the first trimester of gestation. Clinical presentation, in persistently infected cattle (PI), is highly variable. The reasons for this variation is largely unknown. The BVDV circulating in PI exist as quasispecies (swarms of individual viruses). An outbreak resulting in 34 PI cattle presented an opportunity to compare a large number of PI׳s. Methods were developed to compare the circulating viral populations within PI animals. It was found that PI animals generated in the same outbreak carry circulating viral populations that differ widely in size and diversity. Further, it was demonstrated that variation in PI viral populations could be used as a quantifiable phenotype. This observation makes it possible to test the correlation of this phenotype to other phenotypes such as growth rate, congenital defects, viral shed and cytokine expression.

Ovarian regulation of postcoital gonadotropin release in the rabbit: reexamination of a functional role for 20 alphadihydroprogesterone.

In the rabbit, it has proposed that an ovarian progestin, 20 alpha-dihydroprogesterone (20alphaP), released at mating, is essential for a normal postcoital LH surge. However, we measured plasma levels of LH and 20alphaP after mating in rabbits and observed that the frequency, magnitude and time-course of changes in circulating levels of 20alphaP seemed inappropiate to account for the rapid and major surge of LH secretion. This prompted us to re-evalute the role of the ovary in regulating postcoital LH secretion. In chronically ovariectomized (greater than 30 days) does pretreated with estrogen, mating induced a normal LH surge in only 1 of 10 animals, indicating that an ovarian product in addition to estrogen is required for a normal postcoital LH surge. However, when 20alphaP was injected soon after mating in chronically ovariectomized does pretreated with estrogen, only 2 of 9 displayed normal LH surges; this proportion is not different from that (1/10) observed with estrogen treatment alone. To demonstrate that the estrogen treatment, which produced supraphysiologic plasma estradiol levels, did not itself block LH release, 6 intact anestrus females were treated with the same estrogen regimen. Estrus was induced in 5 and each displayed a large post-coital LH surge and ovulated. As a final test of the 20alphaP hypothesis, 5 spontaneously estrous does were ovariectomized within 15 min post coitum to abolish acute increases in circulating ovarian hormones. Three animals released LH in amounts and temporal pattern indistinguishable from intact estrous does. A fourth released smaller amounts of LH. Two of 4 sham-operated does also had normal LH surges. These findings indicate that ovarian hormones are required before mating to support the capacity of the LH secretory mechanism to respond to coitus. Chronic alteration in the hormonal milieu by ovariectomy appears to produce a change in the hypothalamo-hypophysial complex that is not reversed by estrogen, alone. More importantly, these results demonstrate clearly that neither 20alphaP nor any other ovarian hormone is required post coitum, at least after 15 min, for normal LH release.

Gonadotropin-releasing hormone-induced desensitization may account for the decrease in pituitary responsiveness after the preovulatory luteinizing hormone surge.

The LH secretory response of gonadotropes to GnRH varies during the estrous cycle of the rat. The increased secretion of estrogens during the 24-48 h before the preovulatory surge of LH secretion and the enhanced quantities of progesterone secreted acutely during the surge elevate the responsiveness of hypophysial gonadotropes to GnRH. However, the cause of the massive decline in GnRH responsiveness that occurs during or after the surge remains unknown. In the present studies, we investigated the possibility that it is due to GnRH-induced desensitization of gonadotropes. Dispersed pituitary cells from proestrous and estrous rats were preincubated with GnRH (3 or 6 h, 10(- 10) or 10(-9) M), progesterone (13 h, 100 or 200 nM), GnRH plus progesterone, or medium alone. Then, the cells were retrypsinized to permit performance of the reverse hemolytic plaque assay for measurement of LH secretin, during which they were treated with GnRH(0,10(-11),10(-10), and 10(-8)M) for 2 h. The cells from estrous animals showed the large decline in GnRH responsiveness typical of that day of the cycle compared to those from proestrous animals (the total amount of LH secreted decreased by 50-70%). Preincubation of cells from proestrous rat pituitary glands with GnRH in concentrations and for durations that were designed to mimic the physiological situation induced a decline in GnRH responsiveness similar to that observed at estrus. Preincubation with progesterone also reduced the pituitary responsiveness to GnRH in a dose-dependent manner, but did not show additive effects with GnRH. Our results suggest that the major increase in GnRH secretion that induces the preovulatory surge of LH secretion may also participate in inducing the major decrease in pituitary responsiveness to GnRH that occurs from proestrus to estrus.

A "critical period" for cervically-stimulated prolactin relase.

To investigate the role of ovarian steroids in the initiation and maintenance of the prolactin surges typical of pseudopregnancy in the rat, the pattern of plasma prolactin concentrations resulting from cervical stimulation of long-term ovariectomized rats was determined. Cervical stimulation of rats, ovariectomized 2-4 weeks previously, at 1900 h (lights on 0600-1800 h) resulted in a surge of prolactin which was initiated 4-6 h later and which was similar in timing and duration to the nocturnal prolactin surge of intact, pseudopregnant rats. Daily prolactin surges continued for 6 days but declined thereafter. Because plasma progesterone levels were elevated significantly after cervical stimulation, the experiment was repeated iin adrenalectomized-ovariectomized rats. Prolactin surges were still observed, demonstrating that ovarian and adrenal steroids are required neither for initiation nor maintenance of prolactin surges after cervical stimulation. Cervical stimulation at different times of the day (1900 h, 2400 h or 0400 h) always resulted in a surge of prolactin which peaked at 0300-0700 h. The latency from cervical stimulation in the peak of the prolactin surge was 8 h for the 1900 h group, 5 h for the 2400 h group, and 3 h for the 0400 h group. Thus, the appearance of prolactin surges is related to the time of day rather than to the time cervical stimulation is applied, demonstrating the existence of a "critical period" for cervically-induced prolactin release.

Termination at midpregnancy of the two daily surges of plasma prolactin initiated by mating in the rat.

The pattern of plasma prolactin following uterine cervical stimulation consists of two surges each day, one nocturnal, occurring between 0100-0900 h (lights on 0600-1800 h), and one diurnal, occurring between 1500-2100 h. This pattern of prolactin continued throughout pseudopregnancy; the last surge was observed on the morning of day 11 (day 1 was taken as the first day of diestrus of pregnancy or pseudopregnancy). Prolactin levels remained low thereafter until the spontaneous proestrous surge on the afternoon of day 12, signalling the onset of a new estrous cycle. In contrast, the two daily prolactin surges did not continue throughout pregnancy, and in fact, were terminated sooner in pregnant animals than in pseudopregnant animals. The last diurnal surge was observed on day 8 while the last nocturnal surge was observed on day 10. The early termination of prolactin surges during pregnancy correlated with the increased secretion of rat placental lactogen. However, placental extracts obtained from day 11 of pregnancy and injected in large doses failed to inhibit prolactin surges in pseudopregnant animals. Prolactin surges also continued for a longer period of time in pseudopregnant rats bearing decidualized uteri than in pregnant animals. Thus, the two major components of pregnancy that differed from pseudopregnancy, that is, the presence of rat placental lactogen or decidual tissue, did not appear to account for the early termination of prolactin surges during pregnancy.

The decrease in hypothalamic dopamine secretion induced by suckling: comparison of voltammetric and radioisotopic methods of measurement.

Previous in situ voltammetric microelectrode measurements of median eminence dopamine release during mammary nerve stimulation of anesthetized lactating rats revealed a transient (1-3 min) 70% decline of dopamine concentrations. This dopamine was believed to be destined for secretion into the hypophysial portal circulation, but direct experimental support for this supposition was lacking. Thus, in the present study, [3H]dopamine release into brief sequential samples of hypophysial portal blood was compared with dopamine release in the median eminence measured by voltammetry. Lactating female rats were urethane anesthetized, and the median eminence pituitary region was exposed. [3H]Tyrosine was injected into a jugular cannula (100 microCi) followed by continuous infusion (5 microCi/min). In a preliminary experiment, this regimen produced a steady state level of [3H]dopamine in the portal blood within 45 min. In subsequent experiments, portal blood was collected as sequential 3-min samples, and electrochemical sampling from a microelectrode placed in the median eminence occurred at 1-min intervals. Electrochemical current resulting from the oxidation of dopamine in the medial median eminence was unvarying throughout the 75-min experiment in control rats (n = 4) and during the 30-min control period preceding mammary nerve stimulation in the other group (n = 4). These results were parallel by [3H] dopamine levels in portal blood during the same periods of time. All animals showed simultaneous decreases in oxidation current and [3H]dopamine levels within 1-4 min after initiation of mammary nerve stimulation (respectively, 35 +/- 7% and 62.5 +/- 5.9%, mean +/- SEM). Significant increases in oxidation current, taking the form of brief 2- to 6-min pulses began within an average of 18.5 min after initiation of stimulation. Similar increases in [3H]dopamine levels in portal blood were also observed. These and earlier results demonstrate that mammary nerve stimulation (and by extension, suckling) induces a momentary, but profound, decrease in hypothalamic dopamine secretion which precedes or accompanies the rise in PRL secretion evoked by the same stimulus.