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L J Heffner

Publications and source records attributed to L J Heffner.

12 recordsLinked to original sources

Secretion of prolactin and insulin-like growth factor I by decidual explant cultures from pregnancies complicated by intrauterine growth retardation.

OBJECTIVES: Prolactin and insulin-like growth factor I secretion elsewhere in the uterus have been shown to decrease when tissue-specific growth is limited. We investigated their secretion by decidual explant cultures from pregnancies complicated by fetal intrauterine growth retardation. STUDY DESIGN: Explant cultures from 13 pregnancies complicated by intrauterine growth retardation and 12 control pregnancies were established in minimal essential medium and media was harvested after 24 hours of culture. Prolactin and insulin-like growth factor I concentrations were determined by radioimmunoassay. Total protein in the media was also measured. Data were analyzed by analyses of variance and linear regression. RESULTS: Decidual prolactin secretion in the pregnancies with intrauterine growth retardation was reduced to 109 +/- 31 ng/100 mg tissue per 24 hours compared with 254 +/- 51 ng in the controls (p = 0.01). Insulin-like growth factor I secretion was reduced to 1.9 +/- 0.6 ng/100 mg tissue per 24 hours from 7.1 +/- 0.9 ng/100 mg in the controls (p < 0.0001). Total protein secretion did not differ between the two groups. Decidual prolactin and insulin-like growth factor I secretion had a highly significant positive correlation (r = 0.71, p = 0.0001). CONCLUSIONS: Our data show that two protein hormones secreted by the maternal decidua are dramatically reduced in intrauterine growth retardation and warrant further investigation into their roles in the intrauterine environment.

Analysis of Variance

Decreased prolactin secretion by explant cultures of fibroids from women treated with a gonadotropin-releasing hormone agonist.

Endometrium, myometrium and uterine leiomyomata (fibroids) all secrete PRL. Although the regulation of endometrial PRL secretion has been extensively studied, little is known about myometrial and fibroid PRL. This study investigated the effects of the GnRH agonist (GnRH-a) leuprolide acetate depot, administered in vivo, on fibroid and myometrial PRL secretion by explant cultures. Tissue was obtained from 17 patients enrolled in a prospective, randomized, double-blind, placebo-controlled clinical trial. Explant cultures of fibroid and myometrium were established in defined serum free media and harvested media assayed for PRL and total protein. Fibroid PRL secretion was substantially greater than myometrial PRL secretion. Fibroid PRL secretion increased with time whereas myometrial PRL secretion did not. Fibroid, but not myometrial, PRL secretion in GnRH-a treated patients was significantly lower when compared to controls. Fibroid protein secretion was not affected by GnRH-a administration in vivo. Progesterone supplementation in vitro inhibited fibroid PRL secretion; estrogen and GnRH-a in vitro had a minimal effect. Western blot analysis showed a small proportion of PRL secreted by fibroids to be glycosylated. These results demonstrate: 1) PRL secretion is greater from fibroids than myometrium; 2) fibroid PRL secretion in vitro is specifically reduced after 24 h after in vivo treatment with GnRH-a; 3) estrogen or progesterone in vitro does not reverse the suppression by in vivo administration of GnRH-a; and 4) GnRH-a in vitro has no effect on fibroid PRL secretion.

Antineoplastic Agents

The secretion of insulin-like growth factors I and II by explant cultures of fibroids and myometrium from women treated with a gonadotropin-releasing hormone agonist.

The gonadotropin-releasing hormone agonist (GnRH-a) leuprolide acetate depot was used as a biologic probe to investigate the possible roles of insulin-like growth factors (IGFs) I and II in fibroid growth. The secretion of IGF-I and IGF-II by explant cultures of fibroids and myometria from women treated with a GnRH-a was compared with that of tissue obtained from placebo-treated controls. Patients were randomized to receive either leuprolide 3.75 mg every 28 days (N = 9) or placebo injections (N = 8) before myomectomy. Fresh tissue was diced into 2-mm3 explants and cultures were established in serum-free media. The media were assayed for IGF-I, IGF-II, and total protein. Patients treated with GnRH-a demonstrated a 34% reduction in uterine volume, whereas placebo-treated patients exhibited no change. The secretion of IGF-I and IGF-II by fibroid explants obtained from women treated with the GnRH-a was significantly less than that in tissue obtained from placebo-treated controls (P less than .01 and P less than or equal to .05, respectively). Similarly, the secretion of IGF-I and IGF-II by myometrial explants was significantly less in tissue obtained from women treated with GnRH-a (P less than .0001 for both IGF-I and IGF-II). Protein secretion by fibroid tissue obtained from women treated with GnRH-a was not significantly different when compared with tissue from placebo-treated controls. In conclusion, fibroids and myometria from women pretreated with the GnRH-a secreted significantly less IGF-I and IGF-II than did tissue obtained from placebo-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Female

A glycosylated prolactin species is covalently bound to immunoglobulin in human amniotic fluid.

Western immunoblots performed during separation of glycosylated prolactin from amniotic fluid revealed that some of the glycosylated prolactin is covalently bound to another protein. Using high performance liquid chromatography and other protein isolation techniques we have demonstrated that a glycosylated prolactin species is linked to immunoglobulin by disulfide bonds in amniotic fluid.

Amniotic Fluid

Management of isoimmunized pregnancy by use of intravascular techniques.

Twenty-two patients who had 23 pregnancies complicated by isoimmunization were managed by the use of intravascular methods on an outpatient basis. Nine patients underwent 30 percutaneous fetal blood sampling procedures to determine fetal blood type or hematocrit, without complication. Thirteen patients underwent 45 intrauterine fetal transfusions via the umbilical vessels and 16 intraperitoneal fetal transfusions. The overall survival rate in this series was 85.7%. Survival among fetuses that were hydropic at initial evaluation was 83.3%. The procedure-related perinatal mortality rate for intravascular intrauterine transfusions was 2.2%. Knowledge of fetal blood type and hematocrit allowed treatment individualized to the specific needs of each patient. In particular, the ability to transfuse blood directly into the vascular system of the hydropic fetus proved to be lifesaving in those patients.

Blood Grouping and Crossmatching

Early amniocentesis for prenatal cytogenetic evaluation.

Early amniocentesis at 11-14 weeks gestation was evaluated in 100 consecutive patients to see how this technique compares with later amniocentesis. There were no complications as a consequence of the procedure or related pregnancy losses of chromosomally normal fetuses. Samples obtained from three (3%) patients showed insufficient cell growth; two of these patients elected a repeat procedure, which yielded a normal karyotype in each case. There were five abnormal karyotypes, one of which was a culture artifact; in the latter case, repeat amniocentesis at 15 weeks yielded a normal result. Of the 95 pregnancies with normal karyotypes, 94 were progressing normally at follow-up, and one patient elected pregnancy termination because of maternal indications. It appears that early amniocentesis may be an attractive alternative to traditional amniocentesis, in that it provides results at an earlier gestational age and may avoid certain disadvantages of chorionic villus sampling.

Amniocentesis

Electrophoretic analyses of secreted human endometrial proteins: identification and characterization of luteal phase prolactin.

Endometrial protein synthesis and secretion throughout the menstrual cycle was studied by slab gel electrophoretic analysis of [35S]methionine incorporation into protein during short term culture of human endometrial tissue. A minimum of five protein bands that fluctuate during the menstrual cycle were identified on one-dimensional gels. Those with mol wt of 28K, 35K, 51K, and 59K decreased in the luteal phase, whereas a broad 25K band was induced in the luteal phase. This broad band was identified as two species of glycosylated PRL by antihuman PRL immunostaining and [3H]glucosamine incorporation.

Adult

Primary management of postpartum vulvovaginal hematomas by angiographic embolization.

Three cases of large postpartum vulvovaginal hematomas are reported. After conservative measures including incision and drainage, ligation of bleeding sites, vaginal packing and replacement of volume and coagulation factors failed to control the bleeding in each, pelvic angiography was performed. Brisk arterial bleeding demonstrated on arteriography was controlled by Gelfoam embolization in all three cases. Intra- or postpartum hematologic evaluation revealed a previously undiagnosed coagulation disorder in each patient. The authors suggest that angiography be considered before hypogastric artery ligation whenever possible in patients with large postpartum hematomas and that all such patients be evaluated for coagulopathy.

Adult

Effects of neonatal ovariectomy upon 3H-estradiol uptake by target tissues of androgen-sterilized female rats.

Tissue distributions of radioactivity were studied at 2, 4 and 6 h after intravenous injection of 3H-estradiol-17 beta (48.6 ng/100 g b.w.) in 4 groups of 10 or 11 adult female rats with the following neonatal treatments: Control = sham ovariectomy (ovx) on day 1, oil injection on day 5 (n = 10); ovx = ovx on day 1, oil on day 5 (n = 11); TP = sham ovx on day 1, 30 micrograms testosterone propionate (TP) on day 5 (n = 10); ovx-TP = ovx on day 1, 30 micrograms TP on day 5 (n = 11). Neonatal TP treatment significantly hastened vaginal opening in all animals. After ovariectomy, vaginal opening occurred in 20/22 rats regardless of hormonal treatment; ovariectomy did not significantly affect the time of vaginal opening in these 20 animals. All ovariectomized animals had diestrous vaginal smears after puberty, all controls cycled normally and all of the TP group used for the uptake part were in persistent vaginal estrus (sequence of vaginal smears with 70% or more containing no leukocytes) confirmed by ovarian histology to be anovulatory (11/13 injected). 72 h prior to radioisotope injection, intact females in the above groups were ovariectomized and the neonatally ovariectomized were sham operated. Tissue radioactivity was extracted from the anterior, middle and posterior hypothalamus, hippocampus, amygdala, cerebrum, anterior pituitary, uterus and plasma. Neonatal ovariectomy raised 3H-estradiol concentrations in all tissues, except hippocampus and anterior pituitary, suggesting an increase in nonspecifically bound hormone. Neonatal TP decreased 3H-estradiol concentrations in the anterior and middle hypothalamus and uterus only, in both the intact and ovariectomized group, demonstrating a selective effect of neonatal TP upon subsequent development of estrogen binding capacities of target tissues that is independent of the ovaries.

Animals

3H-Estradiol uptake and retention by target tissues of light-sterilized female rats.

Tissue distribution of radioactivity was studied at 2, 4 and 6 h after intravenous injection of 3H-estradiol-17beta (41.7 ng/100 g b.w.) in 12 light-sterilized and 11 control female rats ovariectomized 72 h prior to injection. Female rats were light-sterilized by exposure to continuous illumination for 82 days and, based on the duration of continuous vaginal cornification and the absence of corpora lutea at post-mortem histological examination of the ovaries, were anovulatory for at least 30 days prior to injection. Control rats were housed under conditions similar to the experimentals except that they were exposed to alternating lighting (14 h light:10 h dark). They remained ovulatory throughout the experiment. Uterine 3H-estradiol uptake and retention were significantly depressed in the light-sterilized group. There were no significant differences in 3H-estradiol uptake or retention as a result of light-sterilization in any of the other tissues studied, including anterior, middle, and posterior hypothalamus, hippocampus, amygdala, cerebrum, anterior pituitary and plasma. The failure to detecta reduction in neural 3H-estradiol uptake demonstrates that the anovulatory state can exist without a concomitant reduction in the hypothalamic estrogen binding capacity. The possibility is discussed that the decreased target tissue binding noted in various types of anovulatory animals is the result, not the cause, of altered ovarian function.

Amygdala