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J C Porter

Publications and source records attributed to J C Porter.

At least 55 records · Page 3Linked to original sources
PubMed1990

Expression of tyrosine hydroxylase in cultured brain cells: stimulation with an extractable pituitary cytotropic factor.

Expression of tyrosine hydroxylase (TH) in cultured cells of the ventral hypothalamus-midbrain of fetal rats has been investigated. TH mRNA and TH were quantified by an S1 nuclease protection assay and an immunoblot assay, respectively. Dihydroxyphenylalanine (DOPA) and dopamine secretion were evaluated using their rates of accumulation in the culture medium. The rate of accumulation of DOPA was 2-3 times that of dopamine. Inhibitors of TH activity caused a dose-dependent reduction in DOPA secretion. During an 11-week culture of dissociated cells, TH mRNA increased from 1.6 to 2.8 attomole/well between the first and fourth week of culture, remained steady to the ninth week, and then declined. TH increased from 12 to 105 fmol/well between the first and seventh week and then declined. DOPA secretion increased until the sixth week and then remained steady to the tenth week. An extract of rat pituitaries stimulated DOPA secretion by the cultures in a dose-dependent manner. This activity, attributed to a cytotropic factor (CTF), was inactivated by heating for 10 min in a boiling water bath, but was unaffected by trypsin digestion. Incubation with CTF for 24, 48, 72, and 96 h resulted in a day by day increase in the secretion of DOPA. After 96 h of culture with CTF, the amount per well of TH mRNA, but not TH, was significantly (P less than 0.01) greater than the control value. Pituitary CTF is probably not PRL, since rat PRL did not appreciably affect DOPA secretion or the amount of TH mRNA or TH in the cells. Withdrawal of CTF from CTF-stimulated cells resulted in a marked reduction in DOPA secretion as well as a decrease in TH mRNA. These results support the hypothesis that the pituitary gland contains a cytotropic factor that stimulates TH expression in fetal brain cells of the hypothalamus-midbrain.

Animals↗
PubMed1989

Prolactin levels in umbilical cord blood of human infants: relation to gestational age, maternal complications, and neonatal lung function.

The ontogeny of serum prolactin and its relation to several variables, especially lung function, in 543 neonates was studied. Umbilical cord serum prolactin levels rose between 24 and 42 weeks' gestation, correlating significantly (p less than 0.001) with gestational age (r = 0.44) and birth weight (r = 0.32). Among infants of similar ages, however, there was no variation in serum prolactin level as a function of birth weight, sex, Apgar scores, or delivery method. Infants of women with pregnancy-induced hypertension had higher than normal prolactin levels; infants of diabetic women had normal prolactin levels. At 31.5 to 37 weeks' gestation, infants who developed respiratory distress syndrome had lower serum prolactin levels than those whose lung function was normal or else was abnormal from causes other respiratory distress syndrome. The risk for respiratory distress syndrome was higher in newborns whose prolactin level was low (10th percentile) than in infants whose prolactin level was high (90th percentile). These results are suggestive that prolactin may play a role in fetal lung maturation.

Apgar Score↗
PubMed1989

Endocrine maturation and lung function in premature neonates of women with diabetes.

Because respiratory distress syndrome may result, in part, from a hormonal deficiency in the developing fetus, we investigated the endocrine millieu of 28 infants of women with diabetes who were delivered prematurely (34 to 37 weeks of gestation). The umbilical serum concentrations of estrone, estradiol, estriol, cortisol, and prolactin in infants of women with diabetes who developed respiratory distress syndrome (n = 6) were lower than those in infants of women with diabetes who had normal lung function. Serum hormone levels in age-matched newborns of normal women were higher than those in the infants of women with diabetes with respiratory distress syndrome but were not different than those in the infants of women with diabetes with normal lung function. Plasma glucose levels were highest in women whose neonates developed respiratory distress syndrome. An inverse correlation existed between maternal glucose levels and lecithin-sphingomyelin ratios in amniotic fluid. Thus diabetes occasionally results in significantly delayed maturation of the fetal endocrine milieu. In these instances, delayed fetal lung maturation is a frequent occurrence. Moreover, both phenomena may be related to the extent of diabetic control during pregnancy.

Endocrine Glands↗
PubMed1989

Mass and in situ molar activity of tyrosine hydroxylase in the median eminence. Effect of thyroidectomy and thyroid hormone replacement.

The effects of thyroidectomy and thyroid hormone replacement on the mass and in situ molar activity of tyrosine hydroxylase (TH) in the median eminence (ME) and superior cervical ganglia (SCG) of male rats were investigated. The tissue specificity of these effects were evaluated by comparing the ME with the superior cervical ganglion (SCG). All animals were thyroparathyroidectomized (Tx) or sham Tx. Tx rats were treated daily for 3 weeks with 0.15 M NaCl (solvent vehicle) or L-thyroxine (T4). Two doses of T4, 10 and 100 micrograms/day/kg BW, were used. Sham Tx rats were treated with 0.15 M NaCl. All animals were studied on the day following the last treatment. The mass of TH was determined using an immunoblot assay, and the in situ activity of TH was calculated from the rate of intracellular accumulation of L-dihydroxyphenylalanine (DOPA) after administration of an inhibitor of DOPA decarboxylase activity. In the ME, thyro-parathyroidectomy resulted in a 40% increase in the mass and a 100% increase in the in situ molar activity of TH over that of sham Tx rats. Compared to Tx animals given 0.15 M NaCl, Tx rats treated with a low dose of T4 (10 micrograms/day/kg BW) had a reduced quantity of TH in the ME, but the molar activity of the enzyme was increased. Treatment of Tx rats with a high dose of T4 (100 micrograms/day/kg BW) restored TH mass but not the in situ activity of TH in the ME to the level seen in sham Tx rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Hormonal control of tyrosine hydroxylase in the median eminence: demonstration of a central role for the pituitary gland.

In intact male rats the concentration of dopamine in hypophysial portal plasma of animals treated simultaneously with estradiol and progesterone was twice that of animals treated with the solvent vehicle. Treatment with estradiol or progesterone alone had no effect on dopamine in portal plasma. The rate of synthesis of dihydroxyphenylalanine (DOPA), the precursor of dopamine, in tuberoinfundibular dopaminergic (TID) neurites in the median eminence (ME) was 15 +/- 1.0 (mean +/- SE) pmol DOPA/ME.h in estradiol-progesterone-treated animals compared to 3.2 +/- 0.02 in vehicle-treated controls. Treatment with estradiol or progesterone alone gave a result similar to that seen in controls. In hypophysectomized animals treated with estradiol and progesterone, DOPA synthesis in the ME was greatly attenuated compared to that in intact rats. The in situ activity of tyrosine hydroxylase (TH; expressed as moles of DOPA per mol TH/h) in the ME was 178 +/- 16.5 in estradiol-progesterone-treated intact rats, but was 27 +/- 2.4, 52 +/- 4.2, and 35 +/- 2.5 in animals treated with the solvent vehicle, estradiol, and progesterone, respectively. In hypophysectomized rats the in situ activity of TH in the ME of animals treated with estradiol and progesterone was 53 +/- 8.4, which was significantly (P less than 0.01) less than that in similarly treated intact animals. The circulating PRL level in vehicle-treated animals was 35 +/- 4.6 ng/ml compared to 121 +/- 16 in estradiol-treated animals and 133 +/- 12.2 in estradiol- and progesterone-treated rats, indicating that the difference in the effects of estradiol and estradiol-progesterone on dopamine release, DOPA synthesis, and in situ TH activity was not solely due to a difference in circulating PRL levels. Maintenance for 7 days of anterior pituitary tissue as a graft in a lateral ventricle of intact rats resulted in a 2-fold increase in the synthesis of DOPA and TH activity in the ME compared to that in animals with liver implants. Results obtained in hypophysectomized animals with implants were similar to those in intact animals. The concentrations of PRL in cerebrospinal fluid of intact rats and hypophysectomized rats with anterior pituitary implants in the lateral ventricles were 96 +/- 32 and 127 +/- 35 ng/ml, respectively, which was significantly (P less than 0.001) greater than those in animals with liver implants. We suggest that a factor of pituitary origin stimulates TH activity in TID neurons. This stimulation may be due to PRL, but the existence of another stimulatory substance secreted by pituitary cells cannot be excluded.

Animals↗
PubMed1988

Developmental expression of bovine adrenocortical steroid hydroxylases. Regulation of P-450(17 alpha) expression leads to episodic fetal cortisol production.

The developmental expression of adrenocortical steroid hydroxylases was studied in bovine fetuses from 40 to 280 days gestational age. The expression of P-450(17 alpha) is first detected at a gestational age of 50 days and reaches a maximum at 60-70 days. The expression of P-450(17 alpha) then declines and is nondetectable at a gestational age of 100 days. P-450(17 alpha) is not expressed again until about 240 days, i.e. shortly before birth (approximately 280 days). P-450scc, P-450c21, P-450(11 beta) and adrenodoxin were present in fetal adrenals throughout gestation. This "on-off-on" pattern of P-450(17 alpha) expression during fetal development was associated with a corresponding episodic production of cortisol. Immunoreactive corticotropin (ACTH) levels in fetal plasma were elevated in small fetuses (corresponding to less than or equal to 100 days) and in near-term fetuses (corresponding to greater than 250 days) compared with those in mid-gestation fetuses. In primary culture, adrenal cells from mid-gestation fetuses contained no detectable P-450(17 alpha) but rapidly responded to ACTH with an increase in P-450(17 alpha) protein and mRNA. The tissue specificity of the developmental patterns is emphasized by the fact that both P-450(17 alpha) and P-450scc were detectable throughout the development of the fetal testes, whereas only P-450scc was detectable in fetal bovine ovary prior to 200 days. Thus, in fetal bovine adrenal it appears that ACTH is the major regulatory factor effecting the intermittent presence of P-450(17 alpha), whereas the presence of the other steroid hydroxylases is either regulated by additional factors or shows a much different sensitivity to ACTH.

Adrenal Cortex↗
PubMed1988

Saline ingestion stimulates the in situ molar activity of tyrosine hydroxylase in the median eminence and superior cervical ganglion.

The effects of drinking saline for 7 days on the mass and in situ activity of tyrosine hydroxylase (TH) in the median eminence (ME) and superior cervical ganglion (SCG) of rats were investigated. TH mass was quantified by immunoblot assay. In situ TH activity was calculated from the rate of intracellular accumulation of L-dihydroxyphenylalanine (DOPA). In rats that drank 10 mM, 30 mM, and 100 mM NaCl for 7 days, TH activity in the ME was 34 +/- 4, 36 +/- 5, and 45 +/- 3 (mean and S.E.M.) mol of DOPA.h-1.mol of TH-1, respectively, compared to 30 +/- 2 for rats that drank water. The activity of TH in the SCG of animals that drank 10 mM, 30 mM, and 100 mM NaCl was 143 +/- 24, 167 +/- 12, and 272 +/- 13 mol DOPA.h-1.mol TH-1, respectively, compared to 119 +/- 10 for animals that drank water. The mass of TH in the ME and SCG decreased as a function of the concentration of NaCl in the drinking water. In animals that drank water, 10 mM, 30 mM, and 100 mM NaCl, the amounts (pmol) of TH were, respectively, 0.28 +/- 0.03, 0.31 +/- 0.04, 0.23 +/- 0.02, and 0.21 +/- 0.01 per ME and 0.67 +/- 0.06, 0.72 +/- 0.11, 0.37 +/- 0.01, and 0.34 +/- 0.02 per SCG. TH activity in the ME or SCG was unaffected by treatment for 7 days with arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Increased fetal secretion of ACTH and cortisol by arginine vasopressin.

In the fetus, arginine vasopressin (AVP) has been considered a "stress" hormone with primarily cardiovascular effects. In adult animals, AVP also has substantial endocrine effects, e.g., acting as a corticotropin-releasing factor, an effect not clearly demonstrated in the fetus. Therefore we examined this action of AVP in fetal sheep [135 +/- 1 (SE) days gestation] during a 30-min vasopressin infusion (12 mU/min) while monitoring mean arterial pressure (MAP) and heart rate (HR). Blood samples were obtained before, 15 and 30 min during, and 30 and/or 60 min after the infusion. During vasopressin infusion (n = 11), MAP increased (P less than 0.01), whereas HR fell (P less than 0.01). Plasma AVP increased from 2.32 +/- 0.22 to 84 +/- 6.8 and 89 +/- 10 microU/ml (P less than 0.001), whereas adrenocorticotropin (ACTH) rose from 18.0 +/- 2.4 to 27.7 +/- 3.7 and 43.4 +/- 8.0 pg/ml (P less than 0.05) and cortisol from 1.81 +/- 0.36 to 3.48 +/- 0.56 and 3.97 +/- 0.57 micrograms/dl (P less than 0.005) at 15 and 30 min, respectively. Although neither basal nor AVP-induced ACTH increases changed over the period of gestation studied, base-line cortisol concentrations and the absolute rise in ACTH-stimulated cortisol release increased as gestation progressed, demonstrating increased adrenal sensitivity to ACTH. As in adults, AVP stimulates fetal pituitary secretion of ACTH, providing evidence for another role for AVP in fetal adaptation.

Adrenocorticotropic Hormone↗
PubMed1988

Mass and activity of tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons of the aged brain. Control by prolactin and ovarian hormones.

The roles of prolactin (PRL) and the ovarian hormones, estradiol and progesterone, in the control of tuberoinfundibular dopaminergic neurons of aged female rats were investigated. The in situ molar activity of tyrosine hydroxylase (TH) in neurites of these neurons was assayed by measuring the rate of accumulation of L-dihydroxyphenylalanine in the median eminence following the administration of a L-dihydroxiphenylalanine decarboxylase inhibitor. The TH mass was measured by an immunoblot assay using rat TH as the standard. Pituitary implants in aged ovariectomized animals resulted in a significant increase in the median eminence of both the mass and in situ molar activity of TH. When circulating PRL of aged rats was neutralized by administration of antiserum against rat PRL, the activity of TH was reduced significantly compared to that of animals treated with preimmune serum. In aged ovariectomized rats treated with both estradiol and progesterone, the in situ molar activity of TH increased significantly compared to animals treated only with the solvent vehicle, estradiol, or progesterone. The stimulatory effect of estradiol and progesterone appeared to be mediated through a mechanism that did not involve PRL, since neutralization of circulating PRL failed to prevent an increase in TH activity in estradiol-progesterone-treated animals. None of these treatments affected the in situ activity of TH in the superior cervical ganglion. We conclude that PRL as well as combined estradiol-progesterone treatment have important roles in the maintenance of TH activity in aged tuberoinfundibular dopaminergic neurons.

Age Factors↗
PubMed1988

Mass and in situ activity of tyrosine hydroxylase in the median eminence: effect of hyperprolactinemia.

The role of PRL in the control of catecholaminergic hypothalamic neurons of female rats was investigated. The in situ activity of tyrosine hydroxylase (TH) in neurites of these neurons was assayed by measuring the rate of accumulation of L-3,4-dihydroxyphenylalanine (DOPA) in the median eminence (ME) after the administration of a DOPA decarboxylase inhibitor. The mass of TH was measured by an immunoblot assay using rat TH as the standard. Hyperprolactinemia was induced by pituitaries implanted beneath a renal capsule. Hyperprolactinemia resulted in a significant increase in the in situ activity of TH without an increase in TH mass. The release of dopamine from hypothalamic neurons was assessed by measuring the concentration of dopamine in hypophysial portal plasma. The mean concentration of dopamine in portal plasma of rats bearing pituitary implants was 3 times that in controls. When circulating PRL was neutralized by administration of antiserum against rat PRL, the activity of TH was reduced significantly compared to that in animals treated with preimmune serum. In animals bearing pituitary implants, phosphorylation of TH in the ME was not different from that in control animals. We conclude that the biosynthetic and secretory activities of dopaminergic neurons of the hypothalamus are potentiated by PRL, but the potentiation is not due to an increase in the mass of TH or to the capacity of the neurites of the ME to phosphorylate TH.

Animals↗
PubMed1988

Anti-growth action on mouse mammary and prostate glands of a monoclonal antibody to prolactin receptor.

Monoclonal antibody (PrR-7A) against purified PRL receptor was used in the following studies. When PRL receptor was chromatographed on affinity columns containing PrR-7A antibody or monoclonal antibody against hemocyanin, which served as a control, PRL receptor was bound to the column containing PrR-7A antibody, but not to the column containing control antibody. When solubilized PRL receptor was incubated with PrR-7A antibody, the specific binding of the receptor was reduced 52%. Female mice were treated with the carcinogen, 7,12-dimethylbenz[a]anthracene, and during the succeeding 48 weeks were treated weekly with PrR-7A antibody or control antibody. In the control group 13% developed mammary carcinomas, and 16% developed moderate-to-severe intraductal hyperplasia. No mammary carcinomas were found in the mice treated with PrR-7A antibody, and only 8% of the mice had moderate-to-severe intraductal hyperplasia. Male mice made hyperprolactinemic by implanted pituitary glands were treated weekly with PrR-7A or control antibody. After 7 weeks of treatment, the mean weight of the prostates of mice treated with PrR-7A antibody was 8 +/- 1.1 mg (mean +/- SE), and that of mice treated with control antibody was 27 +/- 3.6 mg. Similar differences were seen in the protein and DNA content of the prostates. These results indicate that PrR-7A antibody is directed against PRL receptor and that immunization with this antibody reduces the incidence of PRL-dependent mammary tumors and preneoplastic ductal hyperplasia and prevents PRL-induced hyperplasia of the prostate.

Animals↗
PubMed1987

Vasopressin and catecholamine secretion during metabolic acidemia in the ovine fetus.

It has been suggested that the substantial rise in fetal plasma arginine vasopressin (AVP) during intrauterine hypoxia/asphyxia reflects decreases in PaO2 and/or pHa; however, the components of these "stresses," i.e. PO2, PCO2, and pH, have not been controlled. Recently, only modest increases in fetal AVP secretion were seen during hypoxia independent of changes in pH and PCO2. Since the independent effects of metabolic acidosis on fetal AVP secretion are unknown, we induced acute metabolic acidemia in fetal sheep at 137 +/- 4 (mean +/- SD) days gestation with 1 M NH4Cl, while monitoring mean arterial pressure, heart rate, PaO2, PaCO2, pHa, plasma osmolality, and blood concentrations of electrolytes, AVP, dopamine, norepinephrine, and epinephrine. Mean arterial pressure, PaO2, PaCO2, and plasma osmolality and sodium were unchanged; pHa decreased from 7.37 +/- 0.01 to 7.04 +/- 0.05 (p less than 0.05) during NH4Cl and did not return to control levels until 24 h later. AVP increased from 2.85 +/- 0.23 to 5.26 +/- 1.11 microU/ml (p less than 0.05) at the time of maximum acidosis, correlating with the fall in pHa (r = -0.67, (p = 0.001); however, after stopping NH4Cl, AVP returned to baseline levels although pHa remained less than 7.15. In control studies using the same osmolar load, volume, and rate of infusion, AVP levels were unchanged. Only epinephrine was significantly (p less than 0.05) elevated during acidosis, but did not correlate with pHa or plasma AVP. Marked metabolic acidemia appears to have little or no effect on fetal AVP secretion, and fetal catecholamine secretion is variable.

Acidosis↗
PubMed1987

In situ steroid sulfatase activity in human epithelial carcinoma cells of vaginal, ovarian, and endometrial origin.

The enzymatic hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate to estrone and dehydroisoandrosterone, respectively, was studied in cells that were derived from four different malignant tumors of the lower reproductive tract of women, viz. a squamous cell vaginal carcinoma, an ovarian carcinoma, and two endometrial adenocarcinomas. These cells had the capacity to hydrolyze both steroid sulfoconjugates. Estrone sulfate was more efficient as a substrate than dehydroepiandrosterone sulfate, since the amount of product formed from estrone sulfate was approximately 3-fold greater than that formed from dehydroepiandrosterone sulfate. Some kinetic parameters of steroid sulfatase were determined in the four cell types and were found to be very similar, as were the rates of hydrolysis. Sulfatase activity was linear with incubation time for at least 2 h and with cell number up to 3.2 X 10(6) cells/mL. The apparent pH optimum of steroid sulfatase, determined by the use of cell sonicates and estrone sulfate as the substrate, was between 6.0 and 7.5. The apparent Km values of steroid sulfatase for estrone sulfate in both squamous vaginal carcinoma cells and ovarian carcinoma cells were both 5 microM, and those for dehydroepiandrosterone sulfate in squamous vaginal carcinoma cells and endometrial adenocarcinoma cells were 6 and 4 microM, respectively. The optimal temperature of steroid sulfatase in squamous vaginal carcinoma cells was 50 C; at this temperature, enzymatic activity was more than twice that at 37 C. The steroid sulfatase pathway that is operative in carcinoma cells in vitro to produce free steroids from steroid sulfate precursors also may serve to produce free steroids in vaginal, endometrial, and ovarian carcinomas in vivo and, perhaps, maintain and stimulate tumor growth.

Adenocarcinoma↗
PubMed1986

Responsiveness of human carcinoma cells of gynecologic origin to 1,25-dihydroxycholecalciferol.

In responsive tissues the induction of 25-hydroxycholecalciferol 24-hydroxylase activity is a marker of 1,25-dihydroxycholecalciferol action. In this study we investigated the responsiveness of various malignant cells, which were derived from carcinomas of gynecologic origin, to 1,25-dihydroxycholecalciferol; we did so because it has been demonstrated that replication of certain malignant human cells that are 1,25-dihydroxycholecalciferol-responsive is inhibited by treatment with this substance. We found that 1,25-dihydroxycholecalciferol treatment caused an increase in 25-hydroxycholecalciferol 24-hydroxylase activity in gynecologic carcinoma cells that were maintained in monolayer culture. The cells were established from ovarian, endometrial, cervical, and vaginal neoplasms. After treatment with 1,25-dihydroxycholecalciferol (10 nmol/L) for 18 hours, the specific activity of 25-hydroxycholecalciferol 24-hydroxylase increased between 2,4- and 49-fold in these cells. This increase in 25-hydroxycholecalciferol 24-hydroxylase activity is suggestive that certain gynecologic malignancies are responsive to 1,25-dihydroxycholecalciferol. We also found, however, that 1,25-dihydroxycholecalciferol did not act to decrease the rate of replication of these cells; indeed in ovarian adenocarcinoma cells, 1,25-dihydroxycholecalciferol caused a decrease in doubling time; in the other cells of this study, there was no effect of 1,25-dihydroxycholecalciferol on cell replication.

Adenocarcinoma↗
PubMed1986

In situ activity and phosphorylation of tyrosine hydroxylase in the median eminence.

Intracellular activation and phosphorylation of tyrosine hydroxylase (TH; E.C. 1.14.16.2) in the median eminence of the rat brain were investigated. The in situ activity of TH was assayed by the accumulation of L-dihydroxyphenylalanine (DOPA) in the median eminence of hypothalamic fragments incubated in the presence of NSD 1015. When hypothalamic fragments were incubated with veratridine (0-10(-3) M), maximal stimulation of TH activity was observed at 10(-4) M. The mean concentration of DOPA in the median eminence of hypothalamic fragments incubated with 10(-4) M veratridine was 3 times that seen in its absence. Phosphorylation of TH in the median eminence was evaluated by autoradiographic quantification of [32P]TH in 32P-labelled median eminence tissue. The amount of [32P]TH in 32P-labelled median eminence incubated with 10(-4) M veratridine was 2 times that seen in the absence of veratridine. These data are consistent with the view that in the median eminence phosphorylation and activation of TH are linked events and that phosphorylation may be a means of regulating the biosynthesis of dopamine in this region of the brain.

Animals↗