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Biomedical subjects

J C Porter

Publications and source records attributed to J C Porter.

At least 91 records · Page 5Linked to original sources
PubMed1983

Dopamine in plasma of lateral and medial hypophysial portal vessels: evidence for regional variation in the release of hypothalamic dopamine into hypophysial portal blood.

The plasma concentrations of dopamine in blood from hypophysial portal vessels in various locations on the pituitary stalk were evaluated in diestrous rats. It was found that the mean concentration of dopamine in blood from lateral hypophysial portal vessels, which contain the venous effluent of the lateral median eminence, was significantly less (P less than 0.005) than that in blood from medial portal vessels, which contain the venous effluent of the medial median eminence [1.59 +/- (SE) 0.23 ng/ml vs. 3.12 +/- 0.48 ng/ml]. The mean plasma concentration of dopamine in blood of lateral portal vessels and of medial portal vessels was at least 20-40 times greater than that in arterial blood of these animals. It was calculated that the rate of release of hypothalamic dopamine was 174 +/- 38 pg/h into a medial portal vessel and 73 +/- 15 pg/h into a lateral portal vessel. The mean plasma concentration of norepinephrine or epinephrine in blood from a medial portal vessel was not different from that from a lateral portal vessel. To address the issue of whether the rate of release of dopamine into a medial portal vessel and into a lateral portal vessel was correlated with the rate of synthesis of dopamine in discrete regions of the median eminence, the concentration of L-dihydroxyphenylalanine (DOPA), the precursor of dopamine, was evaluated in lateral and medial segments of the median eminence of diestrous rats treated with 3-hydroxybenzylhydrazine, an inhibitor of DOPA decarboxylase activity. The concentration of DOPA was similar in the medial and lateral segments of the median eminence, suggesting that the rate of synthesis of dopamine did not account for the difference in the rate of release of dopamine into portal blood. The finding of different concentrations of dopamine in blood from various hypophysial portal vessels may be important in view of the heterogenous perfusion of the pars distalis with hypophysial portal blood. We suggest that topographic differences may exist in the release of PRL by cells of the pituitary gland as a consequence of uneven concentrations of dopamine in portal blood perfusing the lactotropes.

Animals↗
PubMed1982

A reduction in the concentration of immunoreactive corticotropin, melanotropin and lipotropin in the brain of the aging rat.

We have previously shown that the hypothalamic concentration of immunoreactive alpha-melanotropin (alpha-MSHi) is markedly lower in the aging female rat than in the young rat. The current view is that alpha-MSH is derived from corticotropin (ACTH), and ACTH, in turn, is derived from a large molecular-weight precursor (pro-opiocortin); pro-opiocortin also serves as the precursor to beta- and gamma-lipotropin (LPH). To ascertain if the age-related reduction in the concentration of alpha-MSHi may be a result of a decline in the production of pro-opiocortin, we determined the content of immunoreactive ACTH (ACTHi), alpha-MSH (alpha-MSHi), gamma-LPH (gamma-LPHi), and protein, in 3 regions of the brain of young (4 months) and old (26-28 months) female rats: the medial basal hypothalamus (MBH, the region containing the perikarya of the ACTH/MSH/LPH neurons), the preoptic anterior hypothalamus (POA), and the thalamus (regions containing axons of these neurons). The concentration of ACTHi, alpha-MSHi (mol/mg protein), or gamma-LPHi (U/mg protein) in the MBH of old rats was 30-50% of that in the MBH of young rats. Moreover, the concentration of ACTHi, alpha-MSHi or gamma-LPHi in the POA and thalamus of old rats was also lower than that in the POA and thalamus of young rats. Based on these findings, we propose that aging causes a reduction in the production of pro-opiocortin in the brain of the female rat and that such a change may be related to the altered function of the brain of the aged.

Adrenocorticotropic Hormone↗
PubMed1982

Molecular-weight profiles of immunoreactive corticotropin in the hypothalamus of the aging rat.

Extracts of the medial basal hypothalamus (MBH), the preoptic anterior hypothalamus (POA), or the pituitary gland of young (4-month-old) and old (18-month-old) female rats were fractionated on columns of Sephadex G-75 superfine. Five forms of immunoreactive corticotropin (ACTHi) were found in the MBH or POA: greater than 40K, 30-40K, 20-30K, 5.7K, and 4.5K. In contrast, 4 forms of ACTHi were found in the pituitary gland: 30-40K, 20-30K, 5.7K, and 4.5K. Thus, hypothalamic tissue contains a large form of ACTH (greater than 40K ACTH) which is not present in the pituitary gland. We tentatively identified greater than 40K ACTH as a large form of pro-opiocortin, 30-40K ACTH as pro-opiocortin, 20-30K ACTH as ACTH biosynthetic intermediate, 5.7K ACTH as glycosylated ACTH 1-39, and 4.5K ACTH as ACTH 1-39. The content of ACTHi in the MBH and POA of old rats was lower than that of young rats. Nevertheless, regardless of the age of the animals, the fractional amount of 30-40K ACTHi was high in the MBH (a region that includes the presumed site of biosynthesis of pro-opiocortin) compared to that in the POA (a region that is distant to the site of biosynthesis of pro-opiocortin). Moreover, the reduced fractional amount of 30-40K ACTHi in the POA was associated with an increased fractional amount of greater than 40K, 20-30K, 5.7K, and 4.5K ACTHi. These findings are consistent with a precursor-product relationship between the 30-40K ACTHi and 20-30K ACTHi, 5.7K ACTHi, and 4.5K ACTHi.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1982

Defective internalization of low density lipoprotein in epidermoid cervical cancer cells.

Cells of an epidermoid cancer cell line of human uterine cervix, which possessed a high-affinity, specific receptor for low density lipoprotein (LDL), internalized and degraded [125I]iodo-LDL at a very low rate. In these cells, LDL did not stimulate cholesteryl ester synthesis, nor did it suppress 3-hydroxy-3-methylglutaryl coenzyme A reductase to the same extent as in the control cells. The binding of [125I]iodo-LDL by these cells was not decreased by preincubation of the cells in medium containing LDL. Using ferritin-labeled LDL (F-LDL) and electron microscopy, it was determined that at 4 degrees C the cells bound F-LDL in the same way as other cancer cell lines that did not have a defect in internalization. When these cells were warmed to 37 degrees C the F-LDL remained on the surface, whereas in cells from control cancer cell lines the F-LDL was internalized and was no longer observed on the cell surface. On the basis of the results of these studies it is concluded that cells of this epidermoid cancer cell line have a defective ability to internalize LDL.

Binding Sites↗
PubMed1982

Mechanism of arginine vasopressin release in the sheep fetus.

Maternal and fetal plasma concentrations of arginine vasopressin (AVP) during asphyxial and hypoxemic episodes were ascertained between 130 and 140 days of gestation in chronically catheterized sheep. During an acute asphyxial stress, i.e., decreased PaO2 and pHa and increased PaCO2, maternal AVP in plasma was unaltered, whereas fetal arterial plasma concentrations rose from 1.6-2.2 microunits/ml to 34-385 microunits/ml and were associated with massive expulsion of meconium into the amniotic fluid. Mild hypoxemia, induced while the mother breathed a gas mixture consisting of 85% nitrogen and 15% oxygen, did not affect either maternal or fetal plasma AVP concentrations. The use of 10% inspired oxygen resulted in 60% and 50% reductions in maternal and fetal PaO2, respectively (P less than 0.05). In this instance, the maternal plasma AVP levels were unchanged, whereas the fetal plasma AVP concentration rose from a mean of 2.61 +/- 0.14 (SE) to 10.2 +/- 2.59 microunits/ml (P less than 0.025) within 30 min. Expulsion of meconium into the amniotic fluid did not occur. No evidence or either fetal-maternal placental transfer or fetal-placental clearance of plasma AVP was obtained. Although hypoxemic stress resulted in an elevation of fetal plasma AVP concentration, it does not appear to be the sole factor responsible for AVP release during intrauterine stress. It is suggested that substantial elevations in fetal plasma AVP concentrations may play in integral role in the fetal expulsion of meconium into the amniotic fluid.

Acute Disease↗
PubMed1982

Hypothalamic secretion of dopamine after inhibition of aromatic L-amino acid decarboxylase activity.

An accumulation of L-dihydroxyphenylalanine (DOPA) in the median eminence of female rats treated with 3-hydroxybenzylhydrazine (NSD 1015), and inhibitor of aromatic L-amino acid decarboxylase (DOPA decarboxylase) activity, was associated with a decreased concentration of dopamine in the median eminence and pronounced reduction in the release of dopamine into hypophysial portal blood. The amount of dopamine released during 1 h into hypophysial portal blood of vehicle-treated rats represented 18% of the amount of DOPA that accumulated in 1 h in the median eminence of rats treated with NSD 1015. The reduction in the concentration of dopamine in the plasma of blood from a single hypophysial portal vessel after the inhibition of DOPA decarboxylase activity was associated with a concomitant increase in the concentration of PRL in the plasma of arterial blood. In contrast to that of dopamine, the concentration of norepinephrine as well as the concentration of epinephrine in hypophysial portal plasma was the same or slightly greater in animals treated with NSD 1015 than in animals treated with the solvent vehicle. These findings are supportive of the view that the release of dopamine from the tuberoinfundibular neurons is highly dependent on the rate of conversion of DOPA to dopamine and that the rate of synthesis of DOPA is a major factor in the control of the rate of release of dopamine into hypophysial portal blood.

Animals↗
PubMed1981

Cholesterol metabolism in cancer cells in monolayer culture. III. Low-density lipoprotein metabolism.

The metabolism of low-density lipoprotein (LDL) was studied in neoplastic and non-neoplastic cells of human gynecological origin, in monolayer cultures. The neoplastic cells were derived from epidermoid vaginal carcinoma, epidermoid cervical carcinoma and endometrial adenocarcinoma, in various degrees of differentiation. The non-neoplastic cells were cervical fibroblasts and epithelial cells from proliferative endometrial glands. Both neoplastic and non-neoplastic cells assimilated and degraded LDL in a similar fashion to other human cells (e.g. skin fibroblasts). However, the neoplastic cells metabolized LDL at a higher rate than the non-neoplastic cell (e.g. epidermoid cervical cancer cells metabolized LDL at a 20 times higher rate than did cervical fibroblasts). Such a high rate of LDL metabolism probably enables continuously replicating cancer cells to obtain the large amounts of cholesterol required for cell membrane synthesis. If a high rate of LDL metabolism proves to be a general property of cancer cells, such a property could prove useful for tumor chemotherapy, providing cytotoxic chemicals could be incorporated within the LDL molecule.

Adenocarcinoma↗
PubMed1981

Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy.

Adrenocorticotropin (ACTH) and cortisol in plasma were measured weekly from early in gestation through delivery in five women whose pregnancies were normal. During the twelfth week of pregnancy, the concentration of ACTH in plasma of blood samples obtained between 0800 and 0900 hours was 23 +/- 4.6 pg/ml (mean and SEM) and rose progressively to 59 +/- 16 pg/ml at 37 weeks. The levels of ACTH in plasma were significantly lower throughout pregnancy than those found in nonpregnant women. During labor and delivery, ACTH levels rose strikingly to values of 301 +/- 137 pg/ml. As pregnancy advanced, the concentration of cortisol in plasma increased progressively from 149 +/- 34 ng/ml (mean and SEM) at 12 weeks to 352 +/- 90 ng/ml at 26 weeks' gestation but changed minimally thereafter until labor commenced, during which values of 706 +/- 148 ng/ml were achieved. ACTH and cortisol secretory patterns over a 24-hour period were also investigated in one subject during each trimester of pregnancy. Diurnal variations were observed that were qualitatively similar to those seen in nonpregnant women. From the results of these studies, we conclude that ACTH levels are suppressed in plasma of normal pregnant women but are higher in late pregnancy than in early pregnancy. The rise in plasma ACTH concentrations, as pregnancy advances, in spite of increasing levels of plasma cortisol, estrogens, and progesterone, is suggestive of the possibility that a source of ACTH exists that is not subject to negative feedback control, that the clearance of free cortisol increases as pregnancy advances, or that there is an alteration in the metabolism of the ACTH precursor protein produced by the pituitary and/or placenta.

Adolescent↗
PubMed1981

Distribution, subcellular localization and identity of immunoreactive alpha-melanotropin in the pituitary gland and brain.

In homogenates of adult human or rat hypothalamic tissue, immunoreactive alpha-MSH (alpha-MSHi) is concentrated in synaptosomes, suggesting that it is localized in neurons. This conclusion is supported by immunohistochemical results on the localization of alpha-MSHi in the brain. The function of alpha-MSHi in the hypothalamus is undefined but the amount of alpha-MSH in this tissue increases in young rats and decreases in old rats. There is little alpha-MSHi in pituitary glands from human abortuses before the 15th gestational week. Thereafter the amount of alpha-MSHi in the anterior and neurointermediate lobes increases appreciably. When acetic acid extracts of each lobe were analysed by high-pressure liquid chromatography the alpha-MSHi in extracts of the anterior lobe had a retention time equal to that of desacetyl alpha-MSH; little if any alpha-MSHi had a retention time identical to that of desacetyl alpha-MSH; alpha-MSH, if present in these extracts, appeared to be a minor component. A similar analysis of extracts of adult human hypothalamic tissue yielded results suggesting that the alpha-MSHi in this tissue is also attributable largely to desacetyl alpha-MSH.

Adult↗
PubMed1981

Secretion of hypothalamic dopamine into pituitary stalk blood of aged female rats.

Dopamine secreted into the pituitary stalk blood of old constant estrous rats (20-24 months of age) was significantly less than that of young estrous rats (3-4 months of age). Reduced concentrations of dopamine were also observed in the median eminence and in the neurointermediate lobe of the pituitary gland of old female rats compared to those of young female rats. The low rate of secretion of dopamine into pituitary stalk blood of old female rats was associated with high secretion of prolactin into arterial blood. The impaired hypothalamic secretion of dopamine observed in old rats was not affected by increased availability of L-tyrosine. However, when L-DOPA was given to old rats, very high concentrations of dopamine were measured in pituitary stalk blood, whereas the concentrations of dopamine in the arterial blood were very low. On the basis of these data, it is concluded that the neurosecretory activity of the dopaminergic neurons of the hypothalamus is impaired in old constant estrous rats. This impaired activity can be overcome by increasing the availability of L-DOPA but not L-tyrosine.

Aging↗
PubMed1981

Failure of contraceptive steroids to modify human chorionic gonadotrophin secretion by hydatidiform mole tissue and choriocarcinoma cells in culture.

The effect of steroids contained in oral contraceptives, namely ethinylestradiol:17 alpha-ethinyl-1,3,5,(10)-estratriene-3, 17-diol (E) and norethindrone acetate:17 beta-acetoxy-17-ethinyl-4-estren-3-one (N), on cell replication and human chorionic gonadotropin (hCG) secretion by choriocarcinoma cells in monolayer culture and by hydatidiform mole tissue maintained in organ culture were studied. The steroids were added to the culture medium individually or in combination to achieve a range of concentrations (10-10 to 10-4), within and beyond the presumed concentration of these substances in the blood of women taking oral contraceptives. The effect of luteinizing hormone releasing hormone (LHRH) on hCG secretion by choriocarcinoma cells in monolayer culture also was investigated. The rate of hCG production by either choriocarcinoma cells in monolayer culture or by hydatidiform mole tissue maintained in organ culture was not affected by the hormones used in this study; indeed hCG secretion remained reasonably unchanged even with high concentrations of steroids (up to 10-4 M) or LHRH (up to 10-4 mg x ml-1). Cell replication, as measured by increase in amount of cellular protein and DNA, was not stimulated by either of these compounds.

Cell Division↗