Search PubMed⌕ Search

Biomedical subjects

J C Porter

Publications and source records attributed to J C Porter.

At least 109 records · Page 6Linked to original sources
PubMed1981

Characterization of immunoreactive alpha-melanocyte stimulating hormone (alpha-MSHi) in human brain tissue.

Adult human hypothalamic tissue was analyzed for the presence of products generated by post-cleavage processing of ACTH 1-13. The displacement curve generated by immunoreactive alpha-melanocyte stimulating hormone (alpha-MSHi) in extracts (5 M acetic acid or acidified ethanol) of adult human hypothalamic tissue was parallel to the alpha-MSH radioimmunoassay standard curve, and alpha-MSHi eluted as a single peak on Sephadex G-10, G-25, and G-50 columns in a manner identical to that of synthetic alpha-MSH. The alpha-MSHi was clearly distinguishable in its mobility on Sephadex G-50 columns from such peptides as beta-MSH, luteinizing hormone releasing hormone, and ACTH. After high performance liquid chromatography of extracts of hypothalamic tissue from young as well as aged men and women, we found that the major peak of alpha-MSHi (75-95% of total alpha-MSHi) coeluted with desacetyl alpha-MSH (ACTH 1-13 amide) rather than alpha-MSH. We suggest that desacetyl alpha-MSH, rather than alpha-MSH, is the predominant alpha-MSHi in adult human brain tissue.

Adrenocorticotropic Hormone↗
PubMed1981

A model system for the study of the release of luteinizing hormone-releasing hormone from isolated storage granules.

We have developed an in vitro system for the study of the release of luteinizing hormone-releasing hormone (LH-RH) from its storage granules. In this system, homogenates of hypothalamic tissue are subjected to hypoosmotic shock, and the LH-RH-containing granules are isolated by means of differential centrifugation. The isolated granules are then incubated in a buffered medium, and the incubation is terminated by passing the incubation mixture through LH-RH affinity columns. The LH-RH associated with the granules passes freely through the columns, whereas the LH-RH released into the medium binds to the columns and is subsequently eluted with an acid solution. LH-RH is quantified by radioimmunoassay (RIA). We tested the effects of various concentrations of KCl on LH-RH release, which was found to be dependent on the concentration of KCl in the medium over the range 40-160 mM. We then studied the effects of pH on the release of LH-RH. Incubation of granules at pH 7.8 in the presence of 160 mM-KCl resulted in the release from the granules of 14% of the stored LH-RH, whereas incubation at pH 6.2 resulted in the release of approximately 30% of the LH-RH. In addition, granules were incubated at pH 7.8 with MgATP and KCl. MgATP elicited a marked release of LH-RH that was approximately twice that seen in the absence of MgATP. In summary, in this in vitro system, granules containing LH-RH are stable under defined biochemical conditions, and LH-RH release from these granules is stimulated by ions and MgATP.

Adenosine Triphosphate↗
PubMed1981

Role of estrogen in the dopaminergic control of prolactin secretion.

The effect of estrogen on the dopaminergic control of PRL secretion was investigated. Treatment of ovariectomized rats with estradiol benzoate (25 microgram/kg, sc) daily for 5 days resulted in a marked elevation of the serum PRL concentration. This estrogen-induced increase in serum PRL levels was apparently not the result of a suppressed release of dopamine into hypophysial portal blood, since the mean dopamine concentration in hypophysial portal plasma in estrogen-treated rats was 2.5 times that in vehicle-treated animals. It was found that under in vitro conditions, dopamine was much less effective in inhibiting the release of PRL from pituitary glands of estrogen-treated rats than from glands of vehicle-treated controls. The capacity of PRL cells to internalize dopamine and incorporate it into PRL secretory granules was evaluated in anterior pituitary tissue obtained from estrogen- or vehicle-treated animals. When tissue fragments of the anterior pituitary gland were incubated in the presence of dopamine (10(-5) M) for 30 min at 37 C and then homogenized and fractionated by means of continuous sucrose density gradient centrifugation, it was found that the amount of dopamine associated with PRL granules from anterior lobe tissue of estrogen-treated rats was only 40% of that from the tissue of vehicle-treated controls. These results are supportive of the hypothesis that the ability of estrogen to antagonize the inhibitory action of dopamine on PRL secretion is mediated through an estrogen-induced reduction in the capacity of the PRL cell to incorporate dopamine into PRL secretory granules. (Endocrinology 108: 440, 1981)

Animals↗
PubMed1981

Iontophoresis of morphine into the arcuate nucleus: effects on dopamine concentrations in hypophysial portal plasma and serum prolactin concentrations.

The effects of morphine on the release of dopamine from tuberoinfundibular neurons and the release of PRL from the anterior pituitary gland were studied in diestrous female rats. Morphine ions ejected iontophoretically in minute quantities into the arcuate nuclei (using one electrode per nucleus) were found to reduce markedly the concentration of dopamine in hypophysial portal plasma. Thirty minutes after the iontophoretic ejection of morphine using charges of 3.6 and 6.6 millicoulombs/electrode, the concentrations of dopamine in hypophysial portal plasma were reduced 70% and 83%, respectively, relative to the preiontophoretic values. When morphine was iontophoresed into each arcuate nucleus using a charge of 1.5 millicoulombs/electrode, there was no change in the concentration of dopamine in hypophysial portal plasma. The suppressive effect of morphine on dopamine release was prevented by pretreatment of the animals with naloxone (5 mg/kg, ip). In addition to the reduction of the concentration of dopamine in hypophysial portal plasma, the iontophoresis of morphine into the arcuate nuclei enhanced the serum concentration of PRL. On the basis of the present observations, it is suggested that morphine acts on an opiate receptor within the arcuate nucleus to suppress the secretion of dopamine from tuberoinfundibular neurons into hypophysial portal blood, thereby enhancing pituitary gland secretion of PRL.

Animals↗
PubMed1981

Prolactin augmentation of dopamine and norepinephrine release from superfused medial basal hypothalamic fragments.

A superfusion technique was employed in the study of the release of dopamine (DA) and norepinephrine (NE) from medial basal hypothalamic fragments. The DA and NE collected in the superfusion fluid were quantified by a radioenzymatic assay. The amounts of DA and NE released by the medial basal hypothalamic fragments were found to be dependent upon the CA2+ and K+ concentrations in the superfusion fluid. The effect of PRL on the amounts of DA and NE released during exposure to a submaximal stimulus of 30 mM K+ was evaluated. PRL in concentrations of 50-5000 ng/ml augmented the K+-induced release of DA and NE in a concentration-dependent manner. The PRL augmentation of the release of both DA and NE was prevented by the addition of anti-PRL gamma-globulin to the superfusion medium. In view of the inhibitory effect of DA on PRL secretion, these findings are consistent with the conclusion that PRL can influence its own secretion by stimulating the release of hypothalamic DA. The observation that PRL can also augment the release of NE is supportive of the view that PRL can influence the secretion of nondopaminergic neurotransmitters within the hypothalamus.

Animals↗
PubMed1981

Estrogen alters the responsiveness of the anterior pituitary gland to the actions of dopamine on lysosomal enzyme activity and prolactin release.

The effects of dopamine on PRL secretion and lysosomal enzyme activity in anterior pituitary tissue from rats selected during various stages of the estrous cycle were examined under in vitro conditions. During the estrous cycle, there was a marked variation in the capacity of dopamine to stimulate the activity of the lysosomal enzyme beta-glucuronidase in the anterior pituitary gland. Moreover, this variation in the responsiveness of pituitary tissue to the stimulatory action of dopamine on beta-glucuronidase activity was accompanied by a similar variation in the responsiveness of the tissue to the inhibitory action of dopamine on PRL release. Anterior pituitary glands from diestrous rats were the most sensitive to the actions of dopamine on beta-glucuronidase activity and PRL release, whereas glands from estrous animals were the least sensitive. Ovariectomy on the day of diestrus prevented the decline in the responsiveness of the anterior lobe to the actions of dopamine normally seen 2 days later (on the presumptive day of estrus). On the other hand, when animals were treated with estradiol benzoate during the 2 days after ovariectomy, the responsiveness of the pituitary tissue to dopamine was markedly suppressed and was similar to that of tissue from estrous rats. When rats were treated with progesterone during the 2 days after ovariectomy, the responsiveness of the anterior lobe to dopamine was similar to that in ovariectomized controls. It is suggested that the decrease in the responsiveness of the anterior pituitary gland to the actions of dopamine on lysosomal enzyme activity and PRL release that occurs between diestrus and estrus is estrogen mediated. It is also suggested that the ability of estrogen to antagonize the inhibitory effect of dopamine on PRL release may be mediated through an estrogen-induced reduction in the capacity of dopamine to stimulate lysosomal enzyme activity in the anterior pituitary gland.

Animals↗
PubMed1981

Dopamine in hypophysial portal plasma and prolactin in systemic plasma of rats treated with 5-hydroxytryptamine.

Intracerebroventricularly administered 5-hydroxytryptamine (5HT) altered the release of dopamine into pituitary stalk blood and of PRL into the systemic circulation of male rats. The concentration of dopamine in pituitary stalk plasma of rats given 0.5 or 5.0 microgram 5HT was 0.32 +/- 0.06 (mean +/- SE) or 0.18 +/- 0.04 ng/ml, respectively, and was significantly less than that in vehicle-treated animals (0.80 +/- 0.04 ng/ml). Relative to the mean level of PRL in animals injected with the solvent vehicle, the mean concentration of PRL in central venous plasma of rats given 0.5 or 5.0 microgram 5HT was increased 4-fold or 13-fold, respectively. Other rats were infused iv with dopamine for 45 min. After 15 min of infusion, the mean concentration of dopamine in arterial plasma was several times that of dopamine in pituitary stalk plasma of rats not infused with dopamine. Even so, this high concentration of dopamine did not prevent the 5HT-induced release of PRL. We conclude that 5HT modulates the secretion of PRL through a stimulatory mechanism that is effective in the presence of a high plasma concentration of dopamine, a PRL-release inhibiting factor, and suggest that 5HT causes the release of a hypothalamic substance(s) that stimulates release of PRL, i.e. a PRL-releasing factor.

Animals↗
PubMed1981

Sex-related difference in the release of dopamine into hypophysial portal blood.

The concentration of dopamine (DA) in pituitary stalk plasma of cycling female rats during diestrus was approximately 7 times that in stalk plasma of intact male rats, and the rate of DA synthesis in the median eminence of diestrous female rats was 5 times that in the median eminence of intact male rats. DA concentrations in pituitary stalk plasma of castrated adult male rats, orchiectomized as adults or as 1-day-old neonates, did not differ significantly from those of intact adult male rats. However, treatment of male rats with 17 beta-estradiol benzoate for 3 days resulted in a significant (P less than 0.005) increase in the concentration of DA in pituitary stalk plasma. DA concentrations in stalk plasma of adult female rats, ovariectomized as adults or treated with testosterone propionate (50 micrograms) on day 1 of life, did not differ appreciably from those of diestrous female rats. However, DA concentrations in stalk plasma of adult female rats that had been ovariectomized on day 14 of life were significantly (P less than 0.01) lower than those of diestrous female rats. In view of these results, it is concluded 1) that there is a sex-related difference in the release of DA from tuberoinfundibular neurons into hypophysial portal blood, and 2) that this difference is not due to a suppressive action of androgen on the secretion of DA in the male rat, but is a consequence of a stimulatory action of estrogen on the release of DA in the female rat.

Animals↗
PubMed1981

Disproportionate accumulation of immunoreactive corticotropin, melanotropin, and lipotropin in the brain of the maturing rat.

The accumulation of immunoreactive ACTH (ACTHi), alpha MSH (alpha MSHi), and gamma-lipotropin (gamma LPHi) as a function of age (10-120 days) was determined in three regions of the brain of male rats: the medial basal hypothalamus (MBH), the preoptic anterior hypothalamus (POA), and the thalamus. In each region of the brain, the concentrations of ACTHi, alpha MSHi, and gamma LPHi increased with age. In the MBH, the increase occurred in such a manner that the molar ratio of alpha MSHi to ACTHi remained constant regardless of the age of the animals. In contrast, in the POA and thalamus, the increase occurred disproportionately in favor of alpha MSHi, and thus the molar ratio of alpha MSHi to ACTHi was 3 times higher in the adult (120 days old) than in the young (10 or 21 days old) animals. Nevertheless, the ratio of (ACTHi plus alpha MSHi) to gamma LPHi was constant at a level of about 2 regardless of the age of the animal or the region of the brain. Extracts of the MBH or POA were fractionated on columns of Sephadex G-75 superfine. The gel filtration profiles of ACTHi were indicative of the presence of five molecular weight forms of ACTH: greater than 40K, 30-40K, 20-30K, 5.7K, and 4.5K. We tentatively identified greater than 40K ACTH as a large form of proopiocortin, 30-40K ACTH as proopiocortin, 20-30K ACTH as ACTH biosynthetic intermediate, 5.7K as glycosylated ACTH(1-39), and 4.5K ACTH as ACTH-(1-39). Regardless of the age of the animals, the fractional amount of 30-40K ACTH the age of the animals, the fractional amount of 30-40K ACTH was high in the MBH compared to that in the POA. Moreover, the small fractional amount of 30-40K ACTH in the POA was associated with a large fractional amount of small molecular weight forms of ACTHi. However, the predominant form of ACTHi in the POA changed with age: 20-30K ACTH was the major form in the young, whereas 4.5K ACTH was the major form in the adult. These results support the proposal that the production of proopiocortin increases with age, and there is enhanced processing of proopiocortin to ACTH-(1-39) and alpha MSH in the brain of the maturing rat.

Adrenocorticotropic Hormone↗
PubMed1981

The major immunoreactive alpha-melanocyte-stimulating hormone (alpha MSH)-like substance found in human fetal pituitary tissue is not alpha MSH but may be desacetyl alpha MSH (adrenocorticotropin1-13NH2).

Pituitary glands were obtained from human abortuses during the second half of gestation. Acid extracts were made from the anterior and neurointermediate lobes, and alpha MSH immunoreactivity (alpha MSHi) was quantified by RIA. alpha MSHi was found in both lobes of the pituitary gland, with 20-80% of the total pituitary alpha MSHi being present in extracts of the anterior lobe. Anterior and neurointermediate lobe extracts subjected to gel filtration on Sephadex G-50 revealed one peak of alpha MSHi having an elution profile identical to those of alpha MSH and desacetyl alpha MSH (ACTH1-13NH2). To characterize further the alpha MSHi extracts were subjected to high pressure liquid chromatography. No alpha MSH could be identified in extracts of the anterior lobe, and most of the alpha MSHi had an elution profile identical to that of desacetyl alpha MSH. Although small amounts of alpha MSH might be present in the neurointermediate lobe, most of the alpha MSHi in this lobe coeluted with desacetyl alpha MSH. Since alpha MSH was not converted to desacetyl alpha MSH during the extraction and chromatographic procedures, we hypothesize that the predominant form of alpha MSH-like material in the human fetal pituitary gland may be desacetyl alpha MSH.

Adrenocorticotropic Hormone↗
PubMed1981

Age-dependent extinction of thyrotropin-releasing hormone in the human cerebellum.

Immunoreactive TRH was quantified in eight regions of the cerebellum as well as in the medulla, pons, and hypothalamus of the fetal and adult human brain. High levels of TRH were detected in the fetal cerebellum, ranging from 216 +/- 103 pg/mg protein (mean +/- SD) in the deep cerebellar nuclei to 591 +/- 153 pg/mg protein in the anterior vermis. The concentrations of TRH were significantly greater (P less than 0.001) in each of the eight regions of the cerebellum of the fetal brain than in the corresponding regions of the adult brain. The magnitude of the difference between adult and fetal cerebellar levels ranged from an 18-fold difference in the deep cerebellar nuclei to more than a 100-fold difference in the anterior hemisphere. However, the TRH levels in pons and medulla were similar among fetuses and adults, and the TRH concentration in the adult hypothalamus was significantly higher (P less than 0.01) than that in the fetal hypothalamus. The TRH levels in adult rat hypothalami were extremely stable for several hours post mortem. We, therefore, conclude that the differences in cerebellar TRH concentrations of the fetal compared to those of the adult human are not related to a difference in the extent of postmortem degradation of TRH. Rather, we postulate that the decline in cerebellar TRH during maturation is a normal developmental process, and speculate that TRH, which has been found to have diverse effects on the central nervous system, may also influence the development of the human cerebellum.

Adult↗
PubMed1981

Plasma concentrations of 11-deoxycorticosterone in women during the menstrual cycle.

As plasma 11-deoxycorticosterone (DOC) can arise from adrenal secretion and from 21-hydroxylation of plasma progesterone in extraadrenal tissues, alterations in plasma progesterone concentrations might alter significantly the plasma DOC levels in humans. Therefore, the authors measured DOC in plasma of 6 normal, ovulatory women daily throughout their menstrual cycles and in plasma of normal men. The plasma DOC concentrations in women during the follicular phase, when plasma progesterone levels are low, were also low (42 +/- 1.7 pg/ml, mean +/- SE). An increase in the plasma levels of DOC and progesterone occurred at midcycle. The plasma DOC levels remained elevated (P less than .001, as compared with levels during the follicular phase) throughout most of the luteal phase (119 +/- 7.9 pg/ml), declining prior to the onset of menses. However, the plasma levels of cortisol and dehydroepiandrosterone sulfate did not fluctuate during the cycle. The plasma DOC levels in men were 57 +/- 4.3 pg/ml (N = 10). The authors conclude that, during the ovarian cycle of women, significant changes in the plasma levels of DOC occur that are coupled to fluctuations in plasma progesterone concentrations.

Dehydroepiandrosterone↗
PubMed1981

Effect of cell density and confluency on cholesterol metabolism in cancer cells in monolayer culture.

Cholesterol metabolism in four gynecological cancer cell lines in monolayer culture was evaluated as a function of cell density. The rate of uptake and degradation of [125I]iodinated low-density lipoprotein increased during the first 24 to 48 hr of culture, but decreased thereafter. Once the cells became confluent, the rate of metabolism of [125I]iodinated low-density lipoprotein was only one-tenth that in cells which were in the preconfluent state. The specific activity of 3-hydroxy-3-methylglutaryl coenzyme reductase increased during the first 24 to 48 hr of culture and subsequently declined, reaching a nadir after confluency was attained. The rate of incorporation of [14C]oleate into cholesteryl esters was low when the cells were in the log-exponential phase of replication but increased gradually as cell density increased. The highest specific activity of acylcoenzyme A: cholesterol acyltransferase was attained after the cells became confluent. Generally speaking, there was an inverse relationship between the specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the one hand, and the rate of [125I]iodinated low-density lipoprotein metabolism and cholesteryl ester synthesis, on the other. It is concluded that cholesterol metabolism in cancer cells in monolayer culture is regulated, in part, by the rate of cell division. In the cancer cells utilized in this study, it is apparent that cholesterol metabolism was subject to the same regulatory mechanisms as are present in nonneoplastic cells.

Adenocarcinoma↗