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M K Murray

Publications and source records attributed to M K Murray.

29 records · Page 2Linked to original sources

Hormonal control and function of secretory proteins.

The uterus of the pig secretes large amounts of protein in response to progesterone. Estrogen alone has little effect but in combination with progesterone is synergistic at low doses and inhibitory at high doses. The responses of the uterus to progesterone require prolonged hormone treatment and are not immediate. The proteins secreted by the uterus of all species are believed to play some role in the nutritional and developmental support of the conceptuses, particularly during early pregnancy. Such a role is likely to be of greater importance in species such as the pig which possesses a noninvasive, diffuse-type of epitheliochorial placentation. A group of basic polypeptides dominates the uterine secretions of the pig. The best characterized is uteroferrin, a purple colored, iron-containing acid phosphatase which transports iron across the placenta. Three polypeptides which are found associated noncovalently with uteroferrin have been shown to be antigenically closely related to each other and to have arisen from a single precursor polypeptide. Their function is unknown. A family of plasmin/trypsin inhibitors which show sequence homology with bovine pancreatic trypsin inhibitor (aprotinin) has been well characterized and appears to control intrauterine proteolytic events initiated by the conceptuses. Several other proteins secreted in response to progesterone remain to be characterized and functionally defined.

Acid Phosphatase↗

Suppression of lymphocyte activation by a high-molecular-weight glycoprotein released from preimplantation ovine and porcine conceptuses.

A high-molecular-weight (MW greater than 660,000), acidic glycoprotein (HMWGP) was purified from incubation medium of preimplantation, elongating ovine (day 16 and 17) and porcine (day 16) conceptuses. HMWGP was tested for its ability to inhibit [3H-methyl]thymidine incorporation into lymphocytes stimulated by phytohemagglutinin or two-way mixed lymphocyte cultures. Ovine and porcine HMWGP inhibited the incorporation of [3H-methyl]thymidine into lymphocytes in a dose-dependent manner. An approximately 50% inhibition was detected at the lowest dose tested (ovine, 25 micrograms/ml; porcine, 5 micrograms/ml). Complete suppression of thymidine incorporation occurred at the highest doses evaluated (ovine, 200 micrograms/ml; porcine, 40 micrograms/ml). This immunosuppressive effect was not the result of an overall cytotoxic effect on lymphocytes as evaluated by trypan blue exclusion. In conclusion, an ovine and porcine conceptus glycoprotein, HMWGP, has potent in vitro immunosuppressive activity in both phytohemagglutinin and mixed lymphocyte cultures. In vivo, HMWGP may have an immunoregulatory role during early pregnancy in the sheep and pig by providing a local immunosuppressive environment within the uterus to prevent conceptus rejection.

Animals↗

Quantification of an estrogen-dependent cat uterine protein (CUPED) in uterine flushings of estrogen- and progesterone-treated ovariectomized cats by radioimmunoassay.

We previously reported the purification of an estrogen-dependent cat uterine protein (CUPED) and the preparation of a specific anti-CUPED serum in rabbits. Here, we describe a specific radioimmunoassay for CUPED using the purified CUPED and anti-CUPED serum that was utilized to quantify CUPED in daily uterine flushings obtained from steroid-treated ovariectomized cats. The radioimmunoassay was sufficiently sensitive to measure 0.1-100 ng CUPED. CUPED levels were low in untreated ovariectomized cats, increased within one day after the onset of treatment with estradiol, and remained elevated as long as estradiol was unopposed by progesterone. The levels of CUPED decreased when progesterone was added to the treatment regimen either 7, 14, or 28 days after the initiation of estradiol treatment. The data indicate that the presence of CUPED in the uterine flushings is dependent on the presence of estradiol and the absence of progesterone, that CUPED appears in the uterine lumen within one day after the onset of treatment with estradiol, and that the levels of CUPED are sharply reduced within one day of administration of progesterone and become nondetectable after three days.

Animals↗

An indwelling catheter for the collection of cat uterine fluids.

A catheter system is described which allows for repeated samplings of uterine fluids in an awake animal. At laparotomy, catheters were inserted surgically into the ovarian pole of each uterine horn. The catheter ports then were passed through the abdominal wall through a stab incision and tunneled subcutaneously to a midlumbar position on each flank. The common uterine body was ligated to form a closed compartment. Uterine fluids were collected by saline lavage. Approximately 80% of the saline injected into one port was collected from the contralateral port and the catheters functioned successfully in each animal for approximately 45 repeated samplings.

Animals↗

The detection and purification of a cat uterine secretory protein that is estrogen dependent (CUPED).

An estrogen-dependent secretory protein (CUPED) was detected and purified from uterine flushings of ovariectomized cats treated with 17 beta-estradiol. The protein was not detected in uterine flushings obtained from untreated ovariectomized animals or estrogen-primed animals treated with progesterone for 4 days. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of uterine flushings showed the presence of 1 or 2 protein bands with relative mobility values less than reduced and denatured thyroglobulin (Mr = 330,000). The protein was purified by differential centrifugation and gel filtration chromatography. Antiserum was raised against this purified protein in rabbits. The specificity of the antiserum to uterine fluid proteins was assessed by immunoblotting of electrophoretically transferred proteins. The antiserum cross-reacted with electrophoretically separated CUPED protein bands in uterine flushings. This protein may represent the content of the estradiol-induced secretory granules present in endometrial epithelial cells.

Animals↗

The immunocytochemical localization of a cat uterine protein that is estrogen dependent (CUPED).

An estrogen-dependent polypeptide (CUPED), which was purified from uterine flushings of estrogen-treated cats, was localized in endometrial epithelial cells of cats using the peroxidase-antiperoxidase immunocytochemical staining procedure. Epithelial cells from animals treated with estradiol for 4, 7, or 14 days and estrogen-primed animals treated with progesterone for 2 days showed positive immunostaining. Staining was absent in untreated ovariectomized animals and in estrogen-primed animals treated with progesterone for 4 days. Specific cytoplasmic staining was confined to apical secretory granules in nonciliated cells of deep uterine glands. Staining was also commonly observed in the lumen of deep glands. Immunostaining was absent in the cells of the surface epithelium, stroma, and myometrium. In addition, other organs such as the oviduct, kidney, liver, pancreas, and lung showed no evidence of specific immunocytochemical staining. Therefore, the estrogen-dependent polypeptide obtained from uterine flushings of estrogen-treated ovariectomized cats is a uterine-specific secretory product that is packaged in apical cytoplasmic granules of uterine epithelial gland cells before being released into the uterine lumen.

Animals↗

The postovulatory cat oviduct and uterus: correlation of morphological features with progesterone receptor levels.

Oviducts and uteri were obtained from cats at estrus and up to 14 days after coitus. Progesterone binding sites were estimated by Scatchard analysis, serum levels of progesterone were determined by radioimmunoassay, nd key morphological parameters of the lining of the epithelium of the oviduct and the deep uterine glands were quantitated. Progesterone cytosol binding was highest at estrus, significantly depleted by day 4, and continued a gradual decline out to day 14 in both tissues. Nuclear binding was markedly elevated at day 4; with time the binding decreased until by day 14 it was equal to or lower than that detected at estrus. The initial depletion of cytosol binding and rise in nuclear binding coincided with the initial rise in serum progesterone levels. Within the oviduct, the increase in nuclear binding coincided with the onset of regressive changes within the epithelium. These changes included atrophy, deciliation, and apoptosis. Within the uterine glands, the increase in nuclear binding coincided with the onset of the progestational response. This response included cell hypertrophy, glycogen synthesis and deposition, and with longer exposure to elevated levels of progesterone, the disappearance of these glycogen deposits. These results clearly illustrate the immediate effect of low levels of progesterone on the subcellular compartmentalization of the progesterone receptor system, and the down regulation of the total receptor system when target tissues are exposed to a continuous elevation of serum progesterone. These results also illustrate that similar changes in receptor compartmentalization induce different morphological responses within target tissues from the same animal.

Animals↗

Subcellular compartmentalization of the progesterone receptor in cat uteri following the acute administration of progesterone.

Cytosol and nuclear progesterone receptors in the cat uterus were measured by Scatchard analysis to determine the relationships between dose of progesterone administered and the time following administration with the content of receptor in these two cellular compartments. Cats were ovariectomized, treated for 7 days with estradiol and then injected via the saphenous vein with progesterone. One uterine horn was removed prior to, and the other uterine horn after the injection of progesterone. The amount of cytosol receptor translocated was found to be dose-dependent over the range of 0-200 micrograms of progesterone. A maximum of 40% of the cytosol receptor was depleted even when the amount of progesterone injected was increased. In non-estradiol-primed animals it was also found that approximately 40% of the cytosol receptor was depleted following a progesterone injection. Within 3 h of the injection of 300 micrograms of progesterone, the cytosol and nuclear receptor levels had returned to preinjection values. A second administration of progesterone at 1 or 3 h after the first injection of progesterone caused a partial depletion of the cytosol receptor and an increase in nuclear progesterone receptor concentration. These data suggest that the translocation of cytosol receptor and the appearance of nuclear receptor is dose-dependent until approximately 40% of the cytosol receptor is depleted following a single injection of progesterone, that the retention of nuclear receptor after an acute injection of progesterone is of short duration (less than 1 h), and that the replenishment of cytosol receptor is complete within 3 h.

Animals↗

Effects of mentoring on job satisfaction, leadership behaviors, and job retention of new graduate nurses.

Findings from a study on the effects of using mentors to help new graduate nurses adjust to professional nursing revealed improved job satisfaction and increased leadership behaviors. The use of mentors over longer periods to help new nurses make the transition from school to nursing practice is a successful orientation strategy receiving increased attention by nursing staff educators.

Adult↗