The Src homology 2 (SH2) domain containing proteintyrosine phosphatase SHP-2 contributes to prolactin receptor (PRLR) signal transduction to ␤-casein gene promoter activation. We report for the first time that SHP-2 physically associates with the signal transducer and activator of transcription-5a (Stat5a), an important mediator of PRLR signaling to milk protein gene activation, in the mouse mammary HC11 and the human breast cancer T47D cells when stimulated with prolactin (PRL) and human growth hormone, respectively. In addition, overexpression studies indicate that the carboxyl-terminal SH2 domain of SHP-2 is required to maintain tyrosine phosphorylation of Stat5 and its interaction with SHP-2. Furthermore, we demonstrate by nuclear co-immunoprecipitation and indirect immunofluorescence studies that PRL stimulation of mammary cells leads to the nuclear translocation of SHP-2 as a complex with Stat5a. This process was found to involve the catalytic activity of the phosphatase. Finally, using the Stat5 GAS (␥-activated sequence) element of the ␤-casein gene promoter in electrophoretic mobility shift assays, we demonstrate that PRL induces the SHP-2-Stat5a complex to bind to DNA. The presence of the phosphatase in the protein-bound DNA complex was verified by using polyclonal antisera to SHP-2. Our studies indicate a tight physical and functional interaction between SHP2 and Stat5 required for regulation and perpetuation of PRLmediated signaling in mammary cells and suggest a potential role for SHP-2 in the nucleus.

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Immunoreactivities for tyrosine hydroxylase (TH), gamma-aminobutyric acid (GABA) and, in some cases, glutamic acid decarboxylase (GAD) were detected by light and electron microscopy in axons projecting into the median eminence and pituitary gland of various mammals (rats, mice, guinea pigs, cats, rabbits and hares). Light microscope immunoperoxidase reactions were performed on adjacent semithin sections of plastic-embedded samples. In the median eminence external zone, the distributions of the TH- and GAD- or GABA-immunoreactive endings were very similar in the anterior and lateral areas, while medially the GABA-labelled endings predominated. Comparable distribution patterns were found in the various species examined. In the pituitary gland, the distributions of GABA- and TH-immunoreactivities were superimposable in the intermediate lobes of all species examined, except in the rabbit and hare in which both types of innervation were lacking. For electron microscopy, the immunogold procedure was applied to sections of lowicryl-embedded samples; simultaneous detection of GABA- and TH-immunoreactivities was enabled by recto-verso double labelling with gold particles of distinct diameters. In the median eminence, GABA-immunoreactivity occurred systematically in the TH-positive endings, while distinct GABA-positive/TH-negative axons were also detected. In the intermediate lobe, the colocalization of TH- and GABA-immunoreactivities was a constant feature of the axons innervating the melanotrophic cells in all the species examined, except in the Leporidae. The functional significance of this colocalization remains to be determined.

The distribution, morphological features, and morphometric characteristics of cell bodies producing oxytocin (OT) and vasopressin (AVP) were studied in the rabbit hypothalamus by means of a conventional immunoperoxidase method. The aim of the present study was to determine the existence or not of a species-specific OT-cell group that might be involved in the dense OT innervation of the intermediate lobe in the leporidae. No OT-cell group clearly distinct from the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei was found, even in colchicine-treated animals. Most immunoreactive perikarya were found within these nuclei. In addition, small AVP neurons occurred in the suprachiasmatic nucleus. In the SON, the predominant, tightly packed AVP cells occupied the ventral part of the nucleus, whereas OT neurons were dorsolaterally located. The PVN presented a loose organization without any obvious subdivision. OT cells, which predominated, occupied the medial part of the nucleus. The PVN had a prominent rostral anterobasal extension composed mainly of OT cells. Laterally to the nucleus, numerous large AVP neurons, with few and smaller OT cells, dispersed along the neurosecretory tract without forming definite cell clusters. AVP cell bodies had a rough granular aspect contrasting with the smooth and fine one of OT cells. Spinelike processes were rarely observed on the perikarya, except on large scattered AVP neurons, but frequently covered the proximal dendrites of both types of neurons. Throughout the hypothalamus, OT neurons had definitely smaller mean somal areas and were more homogeneous in size than AVP cells.

The aim of this study was to investigate the effects of nocturnal railway noise on cardiovascular reactivity in young (25.8 +/- 2.6 years) and middle-aged (52.2 +/- 2.5 years) adults during sleep. Thirty-eight subjects slept three nights in the laboratory at 1-week interval. They were exposed to 48 randomized pass-bys of Freight, Passenger and Automotive trains either at an 8-h equivalent sound level of 40 dBA (Moderate) and 50 dBA (High) or at a silent Control night. Heart rate response (HRR), heart response amplitude (HRA), heart response latency (HRL) and finger pulse response (FPR), finger pulse amplitude (FPA) and finger pulse latency (FPL) were recorded to measure cardiovascular reactivity after each noise onset and for time-matched pseudo-noises in the control condition. Results show that Freight trains produced the highest cardiac response (increased HRR, HRA and HRL) compared to Passenger and Automotive. But the vascular response was similar whatever the type of train. Juniors exhibited an increased HRR and HRA as compared to seniors, but there was no age difference on vasoconstriction, except a shorter FPL in seniors. Noise level produced dose-dependent effects on all the cardiovascular indices. Sleep stage at noise occurrence was ineffective for cardiac response, but FPA was reduced when noise occurred during REM sleep. In conclusion, our study is in favor of an important impact of nocturnal railway noise on the cardiovascular system of sleeping subjects. In the limit of the samples studied, Freight trains are the most harmful, probably more because of their special length (duration) than because of their speed (rise time).

These results extend those of a previous experiment which showed that intraseptal injections of 8-OH-DPAT impaired spatial reference memory. Based on the characteristics of the observed deficits, it is suggested that the 8-OH-DPAT-induced impairment, rather than being only the result of a true alteration of working memory, might reflect a more global cognitive deficiency in which alteration of general memory capacities may be biased by disrupted search strategies/exploration and/or dysfunctions of attention.

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